European Association Urology Pocket Guidelines 2012

European
Association
of Urology
Pocket Guidelines
2012 edition
Introduction
The EAU Guidelines Office is pleased to present the 2012
edition of the Pocket Guidelines. These ultra-short versions
of Europes most read and used urological clinical Guidelines
have been updated and improved to meet the high standards of the EAU and its members. To maintain this quality,
we advise that the Pocket Guidelines should be used in
combination with the extended documents of the clinical
Guidelines, which are available in hard copy, on CD, and at
the EAU website.
Over 160 contributors have worked throughout the year to
integrate the latest scientific research into the recommendations found in these Pocket Guidelines. Their dedication
and perseverance has resulted in this updated publication;
without them none of this would have been possible. We are
extremely grateful to all contributing panel members who
devote their time and energy to the guidelines project.
The Pocket Guidelines are also published online, at
www.uroweb.org/guidelines/online-guidelines/. to facilitate
consultation of all Guidelines on computer, tablet device, or
smartphone.
The Guidelines Office Board and contributors endeavour

to compile a user-friendly and informative document. We
hope that we have succeeded in making these latest Pocket
Guidelines helpful to you and, ultimately, your patients.
On behalf of the Guidelines Office Board,
Mr. K.F. Parsons
Chairman
EAU Guidelines Office Board

Prof.Dr. J. Irani, Vice-Chairman
Prof.Dr. C.R. Chapple
Prof. M. Fall
Prof.Dr. T. Hnu
Prof.Dr. C. Llorente Abarca
Prof.Dr. T. Loch
Prof.Dr. D. Mitropoulos
Prof.Dr. J. NDow
Prof.Dr. H-P. Schmid
Prof.Dr. R. Sylvester
The European Association of Urology use the following

rating system:
Table 1: Level of evidence*

Level Type of evidence
1a
Evidence obtained from meta-analysis of randomised trials
1b
Evidence obtained from at least one randomised
trial
2a
Evidence obtained from one well-designed controlled study without randomisation
2b
Evidence obtained from at least one other type of
well-designed quasi-experimental study
3
Evidence obtained from well-designed non-experimental studies, such as comparative studies,
correlation studies and case reports
4
Evidence obtained from expert committee reports
or opinions or clinical experience of respected
authorities
*Modified from Sackett et al. (1)
It should be noted, however, that when recommendations are
graded, the link between the level of evidence and grade of
recommendation is not directly linear. Availability of RCTs
may not necessarily translate into a grade A recommendation
where there are methodological limitations or disparity in
published results.
Alternatively, absence of high level evidence does not necessarily preclude a grade A recommendation, if there is overwhelming clinical experience and consensus. In addition,
there may be exceptional situations where corroborating
Introduction
studies cannot be performed, perhaps for ethical or other reasons and in this case unequivocal recommendations are considered helpful for the reader. Whenever this occurs, it has
been clearly indicated in the text with an asterix, as upgraded based on panel consensus. The quality of the underlying
scientific evidence - although a very important factor - has to
be balanced against benefits and burdens, values and preferences and cost when a grade is assigned (2-4).
Table 2: Grade of recommendation*

Grade Nature of recommendations
A
Based on clinical studies of good quality and consistency addressing the specific
recommendations and including at least one randomised trial
B
Based on well-conducted clinical studies, but without randomised clinical trials
C
Made despite the absence of directly applicable
clinical studies of good quality
*Modified from Sackett et al. (1)
References
1. Oxford Centre for Evidence-based Medicine Levels of Evidence (May 2009). Produced
by Bob Phillips, Chris Ball, Dave Sackett, Doug Badenoch, Sharon Straus, Brian Haynes,
Martin Dawes since November 1998. Updated by Jeremy Howick March 2009. [Access
date January 2012]

http://www.cebm.net/index.aspx?o=1025
2. Atkins D, Best D, Briss PA, et al; GRADE Working Group. Grading quality of evidence
and strength of recommendations. BMJ 2004 Jun 19;328(7454):1490.

http://www.ncbi.nlm.nih.gov/pubmed/15205295
3. Guyatt GH, Oxman AD, Vist GE et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924-6.

http://www.ncbi.nlm.nih.gov/pubmed/18436948
4. Guyatt GH, Oxman AD, Kunz R et al; GRADE Working Group. Going from evidence
to recommendations. BMJ 2008 May 10;336(7652):1049-51.

http://www.bmj.com/content/336/7652/1049.long
Non-muscle Invasive Bladder Cancer
Page 21
Upper Urinary Tract Urothelial Cell Carcinomas
Page 30
Muscle-invasive and Metastatic Bladder Cancer
Page 7
Prostate Cancer
Page 48
Renal CellCarcinoma
Page 70
Penile Cancer
Page 89
Page 102
Testicular Cancer
Page 123
Management of Male LUTS,
Page 145
Page 167
Page 176
Page 189
Page 200
Page 224
Page 242
Page 254
Page 278
Page 304
Page 329
incl. benign prostatic obstruction
Male Sexual Dysfunction:
Erectile Dysfunction and Premature Ejaculation
Penile Curvature
Male Infertility
Male Hypogonadism
Urinary Incontinence
Urological Infections
Neurogenic Lower Urinary Tract Dysfunction
Urological Trauma
Pain Management in Urology
Chronic Pelvic Pain
Urolithiasis
Page 365
Renal Transplantation
Paediatric Urology
Page 377
GUIDELINES ON NON-MUSCLEINVASIVE BLADDER CANCER

(Limited text update December 2010)
M. Babjuk, W. Oosterlinck, R. Sylvester, E. Kaasinen,

A. Bhle, J. Palou, M. Rouprt
Eur Urol 2011 Apr;59(4):584-94
Introduction
The EAU Working Group on Non-muscle-invasive Bladder
Cancer has published a short and long version of guidelines
on non-muscle-invasive bladder cancer which contains information on its background, classification, risk factors, diagnosis, prognostic factors, and treatment.
The current recommendations for non-muscle-invasive
bladder cancer are ultra short and are based on the current
literature (until end of 2010), with emphasis being placed
on (evidence based) results from randomised clinical trials
and meta-analyses. These guidelines can be used as a quick
reference on the management of patients with non-muscleinvasive bladder cancer.
The recommendations of this working panel apply to
patients with papillary stage Ta and T1 tumours as well as to
carcinoma in situ (CIS), a flat neoplasm. The classification of
non-muscle-invasive tumours (Ta, T1, and CIS) is given in
Non-muscle-invasive Bladder Cancer
the TNM Classification of Malignant Tumours, 7th Edition,

2009 (Table 1).
Table 1: TNM classification 2009 for urinary bladder

T - Primary Tumour
Non-invasive papillary carcinoma
Ta
Carcinoma in situ: flat tumour
Tis
Tumour invades subepithelial connective tissue
T1
Tumour invades muscularis
T2
T2a Superficial muscle (inner half)
T2b Deep muscle (outer half)
T3 Tumour invades perivesical tissue (beyond muscularis)
T3a Microscopically
T3b Macroscopically (extravesical mass)
T4 Tumour invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall
T4a Prostate, uterus, or vagina
T4b Pelvic wall or abdominal wall
N - Lymph Nodes
NX Regional lymph nodes cannot be assessed
N0
No regional lymph node metatstases
N1
Metastasis in a single lymph node in the true pelvis
(hypogastric, obturator, external iliac, or presacral)
Mestastasis in multiple lymph nodes in the true
N2
pelvis (hypogastric, obturator, external iliac, or presacral)
Metastasis in a common iliac lymph node(s)
N3
M - Distant Metastasis
MX Metastasis not assessed
M0 No distant metastasis
M1 Distant metastasis
Characteristics of stages Ta, T1, and CIS

Stage Ta tumours are confined to the urothelium, have a
papillary configuration of their exophytic part, and do not
penetrate from the urothelium into the lamina propria or
detrusor muscle.
Stage T1 tumours originate from the urothelium but penetrate
the basement membrane which separates the urothelium
from the deeper layers. T1 tumours invade into the lamina
propria, but are not so deep that they reach the detrusor
muscle.
Carcinoma in situ (CIS) is a high-grade (anaplastic) carcinoma confined to the urothelium, but with a flat non-papillary
configuration. Unlike a papillary tumour, CIS appears as reddened and velvety mucosa and is slightly elevated but sometimes not visible. CIS can be local or diffuse. Three types of
CIS are distinguishable;
primary CIS (no previous or concurrent papillary
tumours);
secondary CIS (with a history of papillary tumours);
concurrent CIS (in the presence of papillary tumours).
Characteristics of grade
1973 WHO classification
Apart from their architecture, the individual cells show difNon-muscle-invasive Bladder Cancer
ferent degrees of anaplasia:

Grade 1: well differentiated tumour
Grade 2: moderately differentiated tumour
Grade 3: poorly differentiated tumour
2004 WHOClassification
A new classification system was initially proposed by the
WHO/ISUP in 1998 and updated by the WHO in 2004. For
non-invasive urothelial neoplasias, the categories described
in Table 2 are used.
Table 2: 2004 WHO classification of non-invasive

urothelial neoplasia
Flat lesions
Hyperplasia (flat lesion without atypia or papillary)
Reactive atypia (flat lesion with atypia)
Atypia of unknown significance
Urothelial dysplasia
Urothelial carcinoma in situ (CIS)
Papillary lesions
Urothelial papilloma (a completely benign lesion)
Papillary urothelial neoplasm of low malignant potential
(PUNLMP)
Low-grade papillary urothelial carcinoma
High-grade papillary urothelial carcinoma
The 2004 WHO grading system defines CIS as a non-papillary, i.e. a flat, lesion in which the surface epithelium contains cells that are cytologically malignant. Papillary tumours
are classified as either papillary urothelial neoplasms of low
10 Non-muscle-invasive Bladder Cancer
malignant potential (PUNLMP) or as urothelial carcinomas,

with the latter being subdivided into two grades: low grade
and high grade (Table 2).
The intermediate group (G2) has been eliminated; this group
was the subject of controversy in the 1973 WHO classification. Use of the 2004 WHO classification is advocated, as this
should result in less diagnostic variability among pathologists. However until the 2004 WHO classification has been
validated clinically, both classifications can be used.
The majority of clinical trials published so far on TaT1 bladder tumours have been performed using the 1973 WHO classification, and therefore the following guidelines are based on
the 1973 WHO grade classification.
Diagnosis and initial treatment steps

The diagnosis mainly depends on the cystoscopic examination of the bladder, biopsy, and urine cytology. To date,
molecular urinary markers have not improved the combination of cystoscopy and cytology.
The standard initial therapy for Ta and T1 papillary bladder
tumours is complete macroscopic transurethral resection
(TUR) including a part of the underlying muscle. A second TUR should be considered if there is a suspicion that
the initial resection was incomplete, e.g. when multiple or
large tumours are present, or when the pathologist reported
no muscle tissue in the specimen, or when a high-grade
tumour or a T1 tumour was detected. The technique of
TUR is described in the EAU guidelines on non-muscleNon-muscle-invasive Bladder Cancer
11
invasive urothelial carcinoma of the bladder (Eur Urol 2011

Jun;59(6):997-1008).
The diagnosis of CIS is based on the histology of biopsies
from the bladder wall. Biopsies are taken from suspect areas.
In patients with positive urine cytology and no papillary
tumour, multiple biopsies from normal looking mucosa
including prostatic urethra (random biopsies) are recommended.
Fluorescence cystoscopy is recommended in these cases
as it improves the detection rate of CIS. Urine cytology is an
important tool in the diagnosis and follow-up of CIS because
of its high sensitivity and specificity (over 90%).
Carcinoma in situ cannot be eradicated by TUR and further
treatment is mandatory.
Prognostic factors and adjuvant treatment

TaT1 papillary tumours
Since there is considerable risk for recurrence and/or progression of tumours after TUR, adjuvant intravesical therapy
is recommended for all stages (Ta, T1, and CIS). All patients
should receive an immediate post-operative instillation of
chemotherapy within 6 hours after TUR, except in cases of
bladder perforation or severe bleeding. An immediate instillation is considered as standard, the choice of drug (mitomycin
C, epirubicin, or doxorubicine) is optional.
The choice of further intravesical adjuvant therapy
depends on the patients risk of recurrence and/or progression which can be assessed using the European Organization
for the Research and Treatment of Cancer (EORTC) scor12 Non-muscle-invasive Bladder Cancer
ing system (Table 3) and risk tables (Table 4). Patients with
multiple tumours, large tumours (> 3 cm), and highly recurrent tumours (> 1 recurrence/year) are at the highest risk of
recurrence while patients with stage T1 tumours, high grade
tumours, and CIS have the highest risk of progression.
Intravesical chemotherapy reduces the risk of recurrence but
not progression and is associated with minor side-effects.
Intravesical immunotherapy with Bacillus Calmette-Gurin
(BCG) (induction and maintenance) is superior to intravesical chemotherapy in reducing recurrences and in preventing
or delaying progression to muscle-invasive bladder cancer.
However, intravesical BCG is more toxic.
Recommendations for low risk tumours

Patients with a single, small, low grade Ta tumour
without CIS, who are at low risk for both recurrence
and progression, should receive:
1. A complete TUR.
2. An immediate single post-operative instillation with
a chemotherapeutic agent (drug optional).
3. No further treatment is recommended prior to
recurrence.
GR
A
A
A
Recommendations for high risk tumours

Patients with TaT1 high grade tumours with or without CIS and those with CIS alone are at high risk of
progression. Treatment should consist of:
GR
13
1. Complete TUR of papillary tumours followed by an

immediate post-operative instillation with a chemotherapeutic agent (drug optional).
2. A second TUR after 46 weeks.
3. Adjuvant intravesical immunotherapy with BCG
(full dose or reduced dose in case of side-effects).
Maintenance therapy for at least 1 year is necessary
although the optimal maintenance scheme has not
yet been determined.
4. Immediate cystectomy may be offered to patients at
highest risk of tumour progression.
5. In patients with BCG failure, cystectomy is recommended.
BCG = Bacillus Calmette-Gurin; CIS = carcinoma in situ;
TUR = transurethral resection.
B
A
C
B
Intermediate risk tumours

In the remaining intermediate risk patients, adjuvant intravesical therapy is necessary but no consensus exists regarding
the optimal drug and the most appropriate scheme.
BCG is more effective than chemotherapy in both reducing
recurrence and progression but it is associated with more
systemic and local side-effects.
Recommendations for intermediate risk tumours

The major issue in the management of intermediate
GR
risk tumours is to prevent recurrence and progression,
of which recurrence is clinically the most frequent.
Treatment should include:
1. Complete TUR followed by an immediate postoperative instillation with a chemotherapeutic agent

(drug optional).
2. A second TUR after 46 weeks when the initial
resection was incomplete.
3a Adjuvant intravesical chemotherapy (drug optional), schedule: optional although the duration of
treatment should not exceed 1 year.
Or
3b Adjuvant intravesical immunotherapy with BCG
(full dose or reduced dose in case of side-effects).
Maintenance therapy for at least 1 year is necessary
although the optimal maintenance schedule has
not yet been determined.
B
A
Table 3: Calculation of recurrence and progression

scores
Factor
Number of tumours
Single
2 to 7
>8
Tumour diameter
< 3 cm
> 3 cm
Prior recurrence rate
Recurrence
Progression
0
3
6
0
3
3
0
3
0
3
15
0
0
Primary
< 1 recurrence/year
2
2
2
4
> 1 recurrence/year
Category
Ta
0
0
T1
1
4
Concomitant CIS
No
0
0
Yes
1
6
Grade (1973 WHO)
0
0
G1
0
1
G2
5
2
G3
Total Score
0 - 17
0 - 23
CIS = carcinoma in situ; WHO = World Health Organization.
Table 4: Probability of recurrence and progression

according to total score
Recurrence
score
0
1-4
5-9
10-17
Prob. recurrence 1 year

15%
24%
38%
61%
Prob. recurrence 5 years

31%
46%
62%
78%
Recurrence
risk group
Low risk
Intermediate
risk
High risk
Progression
score
Prob.
progression
1 year
0.2%
Prob.
progression
5 years
0.8%
Progression
risk group
Low risk
2-6
1%
6%
Intermediate
risk
7-13
5%
17%
High risk
14-23
17%
45%
Note: electronic calculators for Tables 3 and 4 are available at
http://www.eortc.be/tools/bladdercalculator/
Eur Urol 2006;49(3):466-77.
Carcinoma in situ
Carcinoma in situ has a high risk of progression to muscleinvasive disease which exceeds 50% in some studies.
BCG intravesical immunotherapy (induction and maintenance) is superior to intravesical chemotherapy in increasing
the complete response rate and the overall percent of patients
remaining tumour free. Moreover, BCG reduces the risk of
progression as compared to either intravesical chemotherapy
or a different immunotherapy. Early radical cystectomy at the
time of diagnosis provides excellent disease-free survival, but
over-treatment occurs in up to 50% of patients.
Recommendations for the treatment of CIS

1. In concurrent CIS, the initial strategy (TUR, early
intravesical instillation, a second TUR) is based on
the features of the papillary tumour.
2. Intravesical BCG immunotherapy including at least
1 year maintenance.
GR
17
3. After the 6 week induction course, a second course B

of 6 weekly BCG instillations or maintenance cycles
consisting of 3 weekly instillations may be considered in non-responders since about 40-60% of these
patients will respond to additional treatment with
BCG.
4. In BCG non-responders at 6 months radical cystec- B
tomy is recommended.
Follow-up for non-muscle-invasive bladder tumours

Patients with non-muscle-invasive bladder tumours need to
be regularly followed up because of the risk of recurrence
and progression; however, the frequency and duration of
cystoscopies should reflect the individual patients degree of
risk. Using the risk tables (Tables 3 and 4), the short-term
and long-term risks of both recurrence and progression in
individual patients can be predicted and the follow-up schedule adapted accordingly:
a. The prompt detection of muscle-invasive and high-grade
non-muscle-invasive recurrences is critical since a delay in
diagnosis and therapy threatens a patients life.
b. Tumour recurrence in the low-risk group is nearly always
low stage and low grade. Small, non-invasive (Ta), low
grade papillary recurrences do not present an immediate danger to the patient and their early detection is not
essential for successful therapy.
c. The result of the first cystoscopy after TUR at 3 months is
a very important prognostic factor for recurrence and for

progression. The first cystoscopy should thus always be
performed 3 months after TUR in all patients with nonmuscle-invasive bladder tumour.
The following recommendations are only based on retrospective experience.
Recommendations for follow-up cystoscopy

Patients with tumours at low risk of recurrence and
progression should have a cystoscopy at 3 months.
If negative, the following cystoscopy is advised at 9
months and consequently yearly for 5 years.
Patients with tumours at high risk of progression
should have a cystoscopy and urinary cytology at 3
months.
If negative, the following cystoscopies and cytologies should be repeated every 3 months for a period
of 2 years, every 4 months in the third year, every 6
months thereafter until 5 years, and yearly thereafter.
A yearly exploration of the upper tract is recommended.
Patients with intermediate-risk of progression (about
one-third of all patients) should have an in-between
follow-up scheme using cystoscopy and cytology,
adapted according to personal and subjective factors.
GR
C
19
Patients with CIS should be followed up for life due

to the high risk of recurrence and progression, both
within the bladder and extravesically. Urine cytology
together with cystoscopy (and bladder biopsies in
cytology positive cases) is essential for monitoring of
treatment efficacy.
The follow-up schedule is the same as for patients
with high-risk tumours.
This short booklet text is based on the more comprehensive EAU guidelines
(ISBN 978-90-79754-96-0), available to all members of the European
Association of Urology at their website, http://www.uroweb.org.
GUIDELINES ON UPPER URINARY

TRACT UROTHELIAL CELL
CARCINOMAS
M. Rouprt, R. Zigeuner, J. Palou, A. Boehle, E. Kaasinen,
M. Babjuk, R. Sylvester, W. Oosterlinck
Eur Urol 2011 Apr;59(4):584-94
Introduction
The EAU Working Group for upper urinary tract urothelial
cell carcinomas (UUT-UCCs) has recently updated guidelines
for this tumour type. This document provides a brief overview of the updated EAU guidelines.
UUT-UCCs are uncommon and account for only 5-10% of
UCCs. The estimated annual incidence of UUT-UCCs in
Western countries is about 1-2 new cases per 100,000 population. Pyelocaliceal tumours are about twice as common as
ureteral tumours.
The principal environmental factors which contribute to the
development of UUT-UCCs are similar to those associated
with bladder cancer, namely tobacco and occupational exposure. Other environmental factors that are specifically associated with UUT-UCCs include phenacetin, aristolochic acid
nephropathy, and blackfoot disease.
Upper Urinary Tract Urothelial Cell Carcinomas
21
The morphology of UUT-UCCs is similar to those of bladder carcinomas. Over 95% of UCCs are derived from the
urothelium, comprising of either UUT-UCCs or bladder carcinomas.
Classification
The classification of UUT-UCCs is given in the TNM classification of Malignant Tumours 7th edition, 2009.
Table 1: TNM classification 2009 for renal pelvis and

ureter*
T - Primary tumour
Primary tumour cannot be assessed
TX
No evidence of primary tumour
T0
Ta
Carcinoma in situ
Tis
T1
Tumour invades muscularis
T2
(Renal pelvis) Tumour invades beyond muscularis
T3
into peripelvic fat or renal parenchyma
(Ureter) Tumour invades beyond muscularis into
periureteric fat
Tumour invades adjacent organs or through the kidT4
ney into perinephric fat
22 Upper Urinary Tract Urothelial Cell Carcinomas
N - Regional lymph nodes

No regional lymph node metastasis
N0
Metastasis in a single lymph node 2 cm or less in the
N1
greatest dimension
Metastasis in a single lymph node more than 2 cm
N2
but not more than 5 cm in the greatest dimension
or multiple lymph nodes, none more than 5 cm in
greatest dimension
Metastasis in a lymph node more than 5 cm in greatN3
est dimension
M - Distant metastasis
*All EAU guidelines advocate the TNM system of tumour classification.
Tumour grade
Until 2004, the most common classification used for UUTUCCs was the WHO classification of 1973, which distinguishes among three grades (G1, G2 and G3). Since 2004,
the new WHO classification distinguishes among three
groups of non-invasive tumours: papillary urothelial neoplasia of low malignant potential, low-grade carcinomas, and
high-grade carcinomas. Both classifications are in use currently for UUT-UCCs. There are almost no tumours of low
malignant potential in the UUT.
Diagnosis
The diagnosis of a UUT-UCC depends on imaging, cystoscopy, urinary cytology, and diagnostic ureteroscopy.
Upper Urinary Tract Urothelial Cell Carcinomas 23
Recommendations for diagnosis of UUT-UCC
GR
Urinary cytology
A
Cystoscopy to rule out a concomitant bladder tumour A
MDCT urography
A
MDCT = multidetector computed tomography.
In addition, the possible advantages of ureteroscopy should
be discussed in the preoperative assessment of any UUTUCC patient.
Prognostic factors
UUT-UCCs that invade the muscle wall usually have a very
poor prognosis. The recognised prognostic factors in decreasing order of importance include:
tumour stage and grade;
concomitant carcinoma in situ (CIS);
age;
lymphovascular invasion;
tumour architecture;
extensive tumour necrosis;
molecular markers;
tumour location;
gender.
Treatment
Localised disease
The radical management of UUT-UCC consists of radical
nephroureterectomy (RNU) by open surgery with excision
of the bladder cuff. This is the gold standard treatment for
UUT-UCC, regardless of the location of the tumour in the
UUT. Resection of the distal ureter and its orifice is per24 Upper Urinary Tract Urothelial Cell Carcinomas
formed because this part of the urinary tract carries a considerable risk of recurrence. Lymph node dissection associated
with RNU is of therapeutic interest and allows for optimal
staging of the disease.
Recommendations for radical management of UUT-UCC:

RNU
Indications for radical management of UUT-UCC
Suspicion of infiltrating UUT-UCC (imaging)
High-grade tumour (urinary cytology)
Multifocality (with two functional kidneys)
Techniques for RNU in UUT-UCC
Open and laparoscopic access are equally effective
Bladder cuff removal is imperative
Several techniques for bladder cuff excision are
acceptable, except stripping
Lymphadenectomy is recommended in the case of
invasive UUT-UCC
GR
B
B
B
B
A
C
C
RNU = radical nephroureterectomy.

The conservative management of low-risk UUT-UCC consists of conservative surgery, which allows for preservation
of the upper urinary renal unit. Conservative management
of UUT-UCC can be considered in imperative cases (renal
insufficiency, solitary functional kidney) or in selected elective cases (functional contralateral kidney) for low-grade,
low-stage tumours. The choice of technique (ureteroscopy,
segmental resection, percutaneous access) depends on technical constraints, the anatomical location of the tumour, and
the experience of the surgeon.
Recommendations for conservative management

of UUT-UCC
Indications for conservative management of UUTUCC
Unifocal tumour
Small tumour (size < 1cm)
Low-grade tumour (cytology or biopsies)
No evidence of an infiltrative lesion on MDCT
urography
Understanding of close follow-up
Techniques used for conservative management of
UUT-UCC
Laser should be used in the case of endoscopic
treatment
Flexible ureteroscopy is preferable to rigid ureteroscopy
Open partial resection is an option for pelvic ureteral
tumours
A percutaneous approach is an option for small, lowgrade, caliceal tumours unsuitable for ureteroscopic
treatment
GR
B
B
B
B
B
C
C
C
C

The instillation of Bacillus Calmette-Gurin (BCG) or mitomycin C in the urinary tract by percutaneous nephrostomy
or via a ureteric stent is technically feasible after conservative
treatment of UUT-UCCs. However, benefits have not been
confirmed.
Advanced disease
There are no benefits of RNU in metastatic (M+) disease,
although it can be considered as a palliative option.
As UUT-UCCs are urothelial tumours, platinum-based chemotherapy is expected to produce similar results to those seen
in bladder cancer. Currently, insufficient data are available to
provide any recommendations.
Radiation therapy appears to be scarcely relevant nowadays
both as a unique therapy and associated with chemotherapy
as tumour adjuvant.
Follow-up
Strict follow-up of UUT-UCC patients after radical management is necessary in order to detect metachronous bladder
tumours (in all cases), local recurrence and distant metastases (in the case of invasive tumours). With conservative
management, the ipsilateral UUT requires careful follow-up
due to the high risk of recurrence.
Recommendations for follow-up of UUT-UCC patients

after initial treatment
After radical management, over at least 5 years
Non-invasive tumour
Cystoscopy/urinary cytology at 3 months and then
yearly
MDCT urography yearly
Invasive tumour
Cystoscopy/urinary cytology at 3 months and then
yearly
GR
C
C
C
MDCT urography every 6 months for 2 years and then C

yearly
After conservative management, over at least 5 years
Urinary cytology and MDCT urography at 3 months, C
6 months and then yearly
C
Cystoscopy, ureteroscopy and cytology in situ at 3
months, 6 months, every 6 months for 2 years and
then yearly
MDCT = multidetector computed tomography; RNU = radical
nephroureterectomy.
Figure 1: Proposed flowchart for the management of UUTUCC

UUT-UCC
Diagnostics evaluation: CT-urography,

urinary cytology, cystoscopy
( ureteroscopy with biopsies)
- Unifocal tumour
- Size < 1 cm
- Low-grade tumour
- Superficial aspect on MDCTU
Gold standard treatment:

Radical nephroureterectomy
Conservative management:
ureteroscopy, segmental resection,
percutaneous approach
Open
Laparoscopic
Recurrence
Close and stringent follow-up
(ISBN: 978-90-79754-96-0), available to all members of the European
MUSCLE-INVASIVE AND METASTATIC

BLADDER CANCER
(Text update February 2012)
A. Stenzl (chairman), J.A. Witjes (vice-chairman),

E. Comprat, N.C. Cowan, M. De Santis, M. Kuczyk,
T. Lebret, M.J. Ribal, A. Sherif
Introduction
Publications concerning muscle-invasive and metastatic
bladder cancer are mostly based on retrospective analysis,
including some larger multicentre studies and well-designed
controlled studies. The studies underpinning the current
guidelines were identified through a systematic literature
research.
It is evident that optimal treatment strategies for MIBC
require the involvement of a specialist multidisciplinary team
and a model of integrated care to avoid fragmentation of
patient care.
Staging system
The UICC 2009 TNM (Tumour, Node, Metastasis
Classification) is used for staging (Table 1).
30 Muscle-invasive and Metastatic Bladder Cancer
Table 1: 2009 TNM classification of urinary bladder

cancer
T - Primary tumour
TX
T0
Ta
Tis
Carcinoma in situ: flat tumour
T1
Tumour invades muscle
T2
T2a Tumour invades superficial muscle
(inner half)
T2b Tumour invades deep muscle
(outer half)
T3
Tumour invades perivesical tissue
T3a Microscopically
T3b Microscopically (extravesical mass)
T4
Tumour invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall
T4a Tumour invades prostate, uterus or vagina
T4b Tumour invades pelvic wall or
abdominal wall
N - Lymph nodes
N0
N1
Metastasis in a single lymph node in the true pelvis
(hypogastric, obturator, external iliac or presacral)
N2
Metastasis in multiple lymph nodes in the true pelvis
(hypogastric, obturator, external iliac or presacral)
Metastasis in a common iliac lymph node(s)
N3
31
Table 2: WHO grading 1973 and 2004

(Both classifications are used for the current guidelines since
most of the retrospective studies were based on the old WHO
1973 grading system).
1973 WHO grading
Urothelial papilloma
Grade 1: well differentiated
Grade 2: moderately differentiated
Grade 3: poorly differentiated
2004 WHO grading
Urothelial papilloma
Papillary urothelial neoplasm of low malignant potential
(PUNLMP)
Low-grade papillary urothelial carcinoma
High-grade papillary urothelial carcinoma
Morphological subtypes can be important for helping with
prognosis and treatment decisions. Currently the following
differentiation is used:
1. urothelial carcinoma (more than 90% of all cases)
2. urothelial carcinomas with squamous and/or glandular
partial differentiation;
3. micropapillary urothelial carcinoma;
4. small-cell carcinomas;
5. some urothelial carcinomas with trophoblastic
differentiation;
6. nested carcinoma:
7. spindle cell carcinomas.
Specific recommendations for primary assessment of presumably invasive bladder tumours

(General information for assessment of bladder tumours, see
EAU Guidelines on Non-muscle-invasive Bladder cancer)
Recommendations
Cystoscopy should describe all macroscopic features
of the tumour (site, size, number and appearance)
and mucosal abnormalities.
A bladder diagram is recommended.
Biopsy of the prostatic urethra is recommended for
cases of bladder neck tumour, when bladder CIS is
present or suspected, when there is positive cytology
without evidence of tumour in the bladder, or when
abnormalities of the prostatic urethra are visible.
If biopsy is not performed during the initial procedure, it should be completed at the time of the
second resection.
In women undergoing a subsequent orthotopic neobladder, procedure information is required (including
a histological evaluation) of the bladder neck and
urethral margin, either prior to, or at the time of
cystoscopy
The pathological report should specify the grade, the
depth of tumour invasion and whether the lamina
propria and muscle tissue are present in the
specimen.
GR
C
Muscle-invasive and Metastatic Bladder Cancer 33
Recommendations for staging of verified bladder GR

tumour
Computed tomography (CT) or magnetic resonance
imaging is recommended if there is suspicion of
locally advanced or metastatic disease precluding
radical treatment.
In patients considered eligible for radical treatment,
for optimal T-staging, either MR imaging with fast
dynamic contrast-enhancement or multidetector
computed tomography with contrast enhancement
are recommended
In patients with confirmed muscle-invasive bladder
cancer, computed tomography of the chest, abdomen
and pelvis is the optimal form of staging, including
CT urography for complete examination of the upper
urinary tracts. If CT is not available, lesser alternatives are excretory urography and a chest X-ray.
In patients with a verified muscle invasive lesion
(TUR), abdominal pelvis and chest imaging is mandatory. MR imaging and CT are equivalent in diagnosing local and distant abdominal metastases.
Computed tomography is preferred to magnetic
resonance imaging for the detection of pulmonary
metastases.
MR = magnetic resonance; CT = computed tomography.
Treatment failure of non-muscle invasive bladder

tumours
Recommendations for treatment failure of nonmuscle invasive bladder cancer
GR
In all T1 tumours at high risk of progression (i.e.

high grade, multifocality, carcinoma in situ, and
tumour size, as outlined in the EAU guidelines for
Non-muscle-invasive bladder cancer), immediate
radical cystectomy is an option.
In all T1 patients failing intravesical therapy,
cystectomy should be performed.
Muscle-invasive bladder cancer - standard treatment

Radical Surgery and Urinary Diversion
Conclusions
For muscle-invasive bladder cancer radical cystectomy is the curative treatment of choice
A higher case load reduces morbidity and mortality
of cystectomy.
Radical cystectomy includes removal of regional
lymph nodes, the anatomical extent of which has not
been sufficiently defined.
Radical cystectomy in both sexes must not include
the removal of the entire urethra in all cases, which
may then serve as outlet for an orthotopic bladder
substitution.
Terminal ileum and colon are the intestinal segments
of choice for urinary diversion.
LE
3
3
3
The type of urinary diversion does not affect

oncological outcome.
Laparoscopic and robotic-assisted laparoscopic
cystectomy is feasible but still investigational.
In patients with invasive bladder cancer older than 80
years cystectomy is an option.
Co-morbidity, age, previous treatment for bladder
cancer or other pelvic diseases, surgeon and hospital
volume of cystectomy, and type of urinary diversion
influence surgical outcome.
Surgical complications of cystectomy and urinary
diversion should be reported in a uniform grading
system. Currently, the best-adapted, graded system
for cystectomy is the Clavien grading system.
3
3
3
2
Contraindications for orthotopic bladder substitution are

positive margins at the level of urethral dissection, positive
margins anywhere on the bladder specimen (in both sexes),
if the primary tumour is located at the bladder neck or in the
urethra (in women), or if tumour extensively infiltrates the
prostate (in men).
Recommendations for radical cystectomy
GR
Radical cystectomy is recommended in T2-T4a, N0
A*
M0, and high risk non-muscle-invasive BC (as outlined above).
Do not delay cystectomy more than 3 months since it B
increases the risk of progression and cancer-specific
death.
Pre-operative radiotherapy is not recommended in

case of subsequent cystectomy with urinary diversion.
Lymph node dissection should be an integral part of
cystectomy, but the extent of the dissection has not
been established.
The urethra can be preserved if margins are negative.
If no bladder substitution is attached, the urethra
must be checked regularly.
Laparoscopic and robot-assisted laparoscopic cystectomy are both options. However, current data have
not sufficiently proven the advantages or disadvantages for both oncological and functional outcomes
of laparoscopic and robotic-assisted laparoscopic
cystectomy.
Before cystectomy, the patient should be fully
informed about the benefits and potential risks of all
possible alternatives, and the final decision should be
based on a balanced discussion between patient and
surgeon.
Pre-operative bowel preparation is not mandatory,
fast track measurements may reduce the time of
bowel recovery.
An orthotopic bladder substitute should be offered to
male and female patients lacking any contraindications and who have no tumour in the urethra and at
the level of urethral dissection.
*Upgraded following panel consensus
Neoadjuvant chemotherapy
Neoadjuvant cisplatin-containing combination chemotherapy
improves overall survival, irrespective of the type of definiMuscle-invasive and Metastatic Bladder Cancer 37
tive treatment (LE: 1a). It has its limitations regarding patient

selection, current development of surgical technique, and
current chemotherapy combinations.
Recommendations
Neoadjuvant chemotherapy should always be
cisplatinum based.
Neoadjuvant chemotherapy is not recommended in
patients with PS > 2 and/or impaired renal function.
GR
A
B
Neoadjuvant/adjuvant radiotherapy in muscle-invasive

bladder cancer
Conclusions
No data exist to support that pre-operative radiotherapy for operable muscle-invasive bladder cancer
increases survival
Pre-operative radiotherapy for operable muscleinvasive bladder cancer, using a dose of 45-50 Gy in
fractions of 1.8-2 Gy results in down-staging after 4-6
weeks.
Pre-operative radiotherapy with a dose of 45-50 Gy in
fractions of 1.8-2 Gy does not significantly increase
toxicity after surgery.
There are suggestions in older literature that preoperative radiotherapy decreases local recurrence of
muscle-invasive bladder cancer.
LE
2
Figure 1: Flowchart for the management for T2-T4a N0M0

urothelial bladder cancer
Diagnosis
Cystoscopy and tumour resection
Evaluation of urethra
CT imaging of abdomen, chest, UUT
MR can be used for local staging
1 - males: biopsy apical prostatic urethra or

frozen section during surgery
1 - females: biopsy of proximal urethra or
frozen section during surgery
Findings:
pT2-3, clinical N0M0 urothelial carcinoma
of the bladder
pT2N0M0 selected patients

- Multimodality bladder sparing therapy
can be considered for T2 tumours
(Note: alternative, not the standard
option)
Neoadjuvant chemotherapy
Should be considered in selected patients
5-7% 5 year survival benefit
2 - neoadjuvant radiotherapy is not

recommended
Radical cystectomy
Know general aspects of surgery
o Preparation
o Surgical technique
o Integrated node dissection
o Urinary diversion
o Timing of surgery
A higher case load improves outcome
Direct adjuvant chemotherapy

Not indicated after cystectomy
Bladder-sparing treatments for localised disease

Transurethral resection of bladder tumour (TURB)
TURB alone is only possible as a therapeutic option if
tumour growth is limited to the superficial muscle layer and
if re-staging biopsies are negative for residual tumour.
External beam radiotherapy

External beam radiotherapy alone should only be considered as a therapeutic option when the patient is unfit for
cystectomy or a multimodality bladder-preserving approach.
Radiotherapy can also be used to stop bleeding from the
tumour when local control cannot be achieved by transurethral manipulation because of extensive local tumour growth
(LE: 3).
Surgically non-curable tumours

Palliative cystectomy for metastatic disease
Primary radical cystectomy in T4b bladder cancer is not a
curative option. If there are symptoms, radical cystectomy
may be a therapeutic/palliative option. Intestinal or nonintestinal forms of urinary diversion can be used, with or
without, palliative cystectomy.
Recommendations
LE
In patients with inoperable locally advanced
tumours (T4b), primary radical cystectomy is a
palliative option and cannot be offered as
curative treatment.
In patients with symptoms palliative cystectomy may be offered.
3
Prior to any further interventions, surgeryrelated morbidity and quality-of-life should be
fully discussed with the patient.
GR
B
Chemotherapy and best supportive care

Urothelial carcinoma is a chemo-sensitive tumour. With
cisplatin-based chemotherapy as primary therapy for locally
advanced tumours in highly selected patients, complete and
partial local responses have been reported. (LE: 2b).
Recommendation
GR
Chemotherapy alone is not recommended as primary A
therapy for localised bladder cancer.
Adjuvant Chemotherapy
Adjuvant chemotherapy is under debate. Neither randomised
trials nor a meta-analysis have provided sufficient data to
support the routine use of adjuvant chemotherapy (LE: 1a).
Recommendation
Adjuvant chemotherapy is advised within clinical
trials, but not as a routine therapeutic option.
GR
A
Multimodality treatment
Conclusions
In a highly selected patient population, long-term
survival rates of multimodality treatment are
comparable to those of early cystectomy.
Delay in surgical therapy can compromise survival
rates.
LE
3
2b
41
Recommendations
Transurethral resection of bladder tumour (TURB)
alone cannot be offered as a standard curative treatment option in most patients.
Radiotherapy alone is less effective than surgery and
is only recommended as a therapeutic option when
the patient is unfit for cystectomy or a multimodality
bladder-preserving approach.
Chemotherapy alone is not recommended as primary
therapy for muscle-invasive bladder cancer.
Surgical intervention or multimodality treatment are
the preferred curative therapeutic approaches since
they are more effective than radiotherapy alone.
Multimodality treatment could be offered as an alternative in selected, well-informed, well selected and
compliant patients, especially for whom cystectomy is
not an option.
GR
B
A
B
Metastatic disease
Conclusions for metastatic disease
LE
Performance status and the presence or absence of
3
visceral metastases are independent prognostic factors
for survival. These factors are at least as important as
the type of chemotherapy administered.
Cisplatin-containing combination chemotherapy is
1b
able to achieve a median survival of up to 14 months,
with long-term disease-free survival reported in about
15% of patients with nodal disease and good
performance status.
Single-agent chemotherapy provides low response

rates of usually short duration.
Carboplatin-combination chemotherapy is less effective than cisplatin-based chemotherapy in terms of
complete response and survival.
Non-platinum combination chemotherapy has produced substantial responses in first- and secondline
use, but has not been tested against standard chemotherapy in fit patients or in a purely unfit patient
group.
To date, there is no defined standard chemotherapy
for unfit patients with advanced or metastatic
urothelial cancer.
Vinflunine reached the highest level of evidence ever
reported for second-line use.
Post-chemotherapy surgery after a partial or complete
response may contribute to long-term disease-free
survival.
Zoledronic acid and denusomab have been studied
and approved for all cancer types including urothelial
cancer, as they have been shown to reduce and delay
skeletal-related events in metastatic bone disease.
2a
2a
2a
2b
1b
3
Recommendations for metastatic disease
GR
The selection of treatment should be guided by prog- B
nostic factors.
First-line treatment for fit patients:
Use cisplatin-containing combination chemoA
therapy with GC, MVAC, preferably with GCSF, or
HD-MVAC with GCSF.
Carboplatin and non-platinum combination chemo- B
therapy are not recommended.
First-line treatment in patients ineligible (unfit) for cisplatin:

Use carboplatin combination chemotherapy or single C
agents.
For cisplatin-ineligible patients (unfit) with either
A
PS 2 or impaired renal function, or with 0-1 poor
Bajorin prognostic factors, first-line treatment is
carboplatin-containing combination chemotherapy,
preferably with gemcitabine/carboplatin.
Second-line treatment:
A*
In patients progressing after platinum-based combination chemotherapy for metastatic disease, vinflunine should be offered. Alternatively, treatment
within a clinical trial setting may be offered.
Zoledronic Acid or denosumab, are recommended for B
the treatment of bone metastases.
*Grade A recommendation is weak by a problem of statistical
significance.
Recommendation for the use of biomarkers

Currently, no biomarkers can be recommended in
daily clinical practice since they have no impact on
predicting outcome, treatment decisions or monitoring therapy in muscle-invasive bladder cancer.
*Upgraded following panel consensus.
GR
A
Figure 2: Flowchart for the management of metastatic

urothelial cancer
Patient characteristics:
PS 0-1/ 2/ >2
GFR >/< 60ml/min
Comorbidities
CISPLATIN?
NO
YES
PS 0 -1 and
GFR > 60ml/min
STANDARD GC
MVAC
HD MVAC
PS 2 or
GFR < 60ml/min
comb. chemo: Carbo- based
NO
PS > 2 and
GFR < 60ml/min
NO comb.chemo
studies, monotherapy, BSC
Second-line treatment
PS > 2
PS 0-1
1. Progression > 6 -12

months after first-line
chemotherapy, adequate
renal function
a. re-exposition to first
line treatment (cisplatin
based)
b. clinical study
2. Progression
> 6 -12 months
after first-line
chemotherapy, PS
0-1, impaired renal
function
a. Vinflunine
b. clinical study
3. Progression
< 6 -12 months
after first-line
chemotherapy,
PS 0-1
a. Vinflunine
b. clinical study
a. best supportive care

b. clinical study
Health-related quality-of-life (HRQoL)

No randomised, prospective HRQoL study has evaluated the
different forms of definitive treatment for muscle-invasive
bladder cancer. Important determinants of (subjective) quality of life are a patients personality, coping style and social
support.
Recommendations for HRQoL

The use of validated questionnaires is recommended
to assess HRQoL in patients with muscle-invasive
bladder cancer.
Unless a patients co-morbidities, tumour variables
and coping abilities present clear contra-indications,
a continent urinary diversion should be offered.
Pre-operative patient information, patient selection, surgical techniques, and careful post-operative
follow-up are the cornerstones for achieving good
long-term results.
Patient should be encouraged to take active part in
the decision-making process. Clear and exhaustive
information on all potential benefits and side-effects
should be provided, allowing them to make informed
decisions.
GR
B
Recommendations for general follow-up

Follow-up is based on the stage of initial tumour after cystectomy. At every visit, the following should be
performed:

history;

physical examination;

bone scan only when indicated.
Tables have been set up (see EAU Guidelines 2012 version),
based on expert opinion which, however, do not include
non-oncological follow-up. They comprise a minimum set of
tests that must be performed during follow-up (GR: C; LE:
4). After 5 years of follow-up, stop oncological surveillance
and continue with functional surveillance.
This short booklet text is based on the more comprehensive EAU guidelines (ISBN978-90-79754-83-0), available to all members of the European
GUIDELINEs ON PROSTATE CANCER

A. Heidenreich (chairman), P.J. Bastian, J. Bellmunt,

M. Bolla, S. Joniau, T.H. van der Kwast, M.D. Mason,
V. Matveev, N. Mottet, T. Wiegel, F. Zattoni
Eur Urol 2008 Jan;53(1):68-80
Eur Urol 2011 Jan;59(1):61-71
Eur Urol 2011 Apr;59(4):572-83
Introduction
Cancer of the prostate (PCa) is currently the second most
common cause of cancer death in men. In developed countries PCa accounts for 15% of male cancers compared with
4% of male cancers in developing countries. Within Europe
exist also large regional differences in the incidence rates of
PCa.
There are three well-established risk factors for PCa: increasing age, ethnic origin, and genetic predisposition. Clinical
data suggest that exogenous risk factors, such as diet, pattern
of sexual behaviour, alcohol consumption, exposure to ultraviolet radiation, and occupational exposure may also play an
important role in the risk of developing PCa.
The introduction of an effective blood test, prostate-specific
antigen (PSA), has resulted in more early-stage prostate cancer diagnosis where potentially curative treatment options
48 Prostate Cancer
can be provided. However, if effective diagnostic procedures

are inappropriately used in elderly men with a short life
span, the issue of over-diagnosis and over-treatment may
occur. Consequently, the same stage of prostate cancer may
require different treatment strategies depending on an individual patients life expectancy.
Staging system
The 7th edition Union Internationale Contre le Cancer
(UICC) 2009 Tumour Node Metastasis (TNM) classification
is used for staging (Table 1).
Table 1: Tumour Node Metastasis (TNM) classification

of cancer of the prostate
T - Primary tumour
TX
T0
T1
T2

Clinically unapparent tumour not palpable or visible
by imaging
T1a Tumour incidental histological finding in 5%
or less of tissue resected
T1b Tumour incidental histological finding in
more than 5% of tissue resected
T1c Tumour identified by needle biopsy (e.g.
because of elevated PSA level)
Tumour confined within the prostate1
T2a Tumour involves one half of one lobe or less
Prostate Cancer 49
T3
T4
T2b Tumour involves more than half of one lobe,

but not both lobes
T2c Tumour involves both lobes
Tumour extends through the prostatic capsule2
T3a Extracapsular extension
(unilateral or bilateral)
T3b Tumour invades seminal vesicle(s)
Tumour is fixed or invades adjacent structures other
than seminal vesicles: external sphinter, rectum,
levator ani and/or pelvic wall
N - Regional lymph nodes3

NX
N0
N1
Regional lymph nodes cannot be assessed

Regional lymph node metastasis
M - Distant metastasis4
M0
M1
No distant metastasis
Distant metastasis
M1a Non-regional lymph node(s)
M1b Bone(s)
M1c Other site(s)
1 Tumour
found in one or both lobes by needle biopsy, but not

palpable or visible by imaging, is classified as T1c.
2 Invasion into the prostatic apex, or into (but not beyond) the
prostatic capsule, is not classified as T3, but as T2.
3 The regional lymph nodes are the nodes of the true pelvis,
which are essentially the pelvic nodes below the bifurcation
of the common iliac arteries. Laterality does not affect the N
classification.
4 When more than one site of metastasis is present, the most
advanced category should be used.
50 Prostate Cancer
Gleason grading system

The most commonly used system for grading PCa is the
Gleason grading system.
Diagnosis and staging

The decision whether to proceed with further diagnostic or
staging work-up is guided by which treatment options are
available to the patient, taking the patients age and comorbidity into consideration. Procedures that will not affect the
treatment decision can usually be avoided.
Synoptic reporting of surgical specimens results in more
transparent and more complete pathology reporting. The use
of a checklist is encouraged and two examples are presented
here.
Checklist for pathology reporting of prostate biopsies
1. Histological type of carcinoma
2. Histological grade (global or highest)
Primary grade
Secondary (= highest) grade
3. Fraction of involved cores
Number of cores involved by carcinoma
Total number of cores
4. Tumour quantification
Percentage of prostatic tissue involved by carcinoma or
total mm of cancer length
5. Tumour extent
Identification of perineural invasion
Identification of extra-prostatic extension
Identification of seminal vesicle invasion
Prostate Cancer
51
Checklist for processing and pathology reporting of radical

prostatectomy (RP) specimens
1. Processing of RP specimens
Total embedding of a prostatectomy specimen is preferred, either by conventional (quadrant sectioning) or
by whole-mount sectioning
The entire surface of RP specimens should be inked
before cutting in order to evaluate the surgical margin
status
The apex should be separately examined using the cone
method with sagittal or radial sectioning
2. Histological type
3. Histological grade
Primary (predominant) grade
Secondary grade
Tertiary grade (if exceeding > 5% of PCa volume)
Global Gleason score
Approximate percentage of Gleason grade 4 or 5
(optional)
4. Tumour quantification (optional)
Percentage of prostatic tissue involved
Tumour size of dominant nodule (if identified), greatest
dimension in mm
5. Pathological staging (pTNM)
Presence of extraprostatic extension (focal or extensive),
specify sites
Presence of seminal vesicle invasion
Presence of lymph node metastases, number of retrieved
lymph nodes and number of positive lymph nodes
6. Surgical margins
Presence of carcinoma at margin
52 Prostate Cancer
If present, specify site(s) and extra- or intra-prostatic

invasion
7. Other
If identified, presence of angioinvasion
Location (site, zone) of dominant tumour (optional)
Perineural invasion (optional)
If present, specify extra- or intra-prostatic invasion

A short summary of the guidelines on diagnosis and staging

of PCa are presented in Table 2.
Guidelines for the diagnosis and staging of PCa

Diagnosis of PCa
GR
1.
An abnormal digital rectal examination (DRE)

result or elevated serum PSA measurement
could indicate PCa. The exact cut-off level of
what is considered to be a normal PSA value
has yet to be determined, but values of approximately < 2-3 ng/mL are often used for younger
men.
2.
The diagnosis of PCa depends on histopathological (or cytological) confirmation.
Biopsy and further staging investigations are

only indicated if they affect the management of
the patient.
Prostate Cancer 53
3.
4.
Transrectal ultrasound (TRUS)-guided systemic

biopsy is the recommended method in most
cases of suspected PCa. At least 8 systemic,
laterally directed, cores are recommended, with
perhaps more cores in larger volume prostates.
Transition zone biopsies are not recommended

in the first set of biopsies due to low detection
rates.
One set of repeat biopsies is warranted in cases

with persistent indication for PCa (abnormal
DRE, elevated PSA or histopathological findings
suggestive of malignancy at the initial biopsy).
Overall recommendations for further (three

or more) sets of biopsies cannot be made; the
decision must be made based on an individual
patient.
Transrectal peri-prostatic injection with a local

A
anaesthetic can be offered to patients as effective
analgesia when undergoing prostate biopsies.
Staging of PCa
1.
Local staging (T-staging) of PCa should be

based on magnetic resonance (MR) imaging.
Further information is provided by the number
and sites of positive prostate biopsies, the
tumour grade and the level of serum PSA.
54 Prostate Cancer
2.
Despite its high specificity in the evaluation

of extraprostatic extension (EPE) and seminal
vesicle invasion or involvement (SVI), TRUS is
limited by poor contrast resolution, resulting
in low sensitivity and a tendency to understage
PCa. Even with the advent of colour- and power
Doppler to assist in identifying tumour vascularity, the accuracy of TRUS in local staging
remains inadequate. In comparison with DRE,
TRUS and computed tomography (CT), MR
imaging demonstrates higher accuracy for the
assessment of uni- or bi-lobar disease (T2), EPE
and SVI (T3), as well as the invasion of adjacent structures (T4). The addition of dynamic
contrast-enhanced MR imaging (DCE-MRI)
can be helpful in equivocal cases. The addition
of magnetic resonance spectroscopic imaging
(MRSI) to MRI also increases accuracy and
decreases inter-observer variability in the evaluation of EPE.
Lymph node status (N-staging) is only important when potentially curative treatment is
planned. Patients with stage T2 or less, PSA
<20 ng/mL and a Gleason score < 6 have a
lower than 10% likelihood of having node
metastases and can be spared nodal evaluation.
Given the significant limitations of pre-operative imaging in the detection of small metastases (<5 mm), pelvic lymph node dissection
(PLND) remains the only reliable staging method in clinically localised PCa.
Prostate Cancer 55
3.
Currently, it seems that only methods of histological detection of lymph node metastases with
high sensitivity, such as sentinel lymph node
dissection or extended PLND, are suitable for
lymph node staging in PCa.
Skeletal metastasis (M-staging) is best assessed

by bone scan. This may not be indicated in
asymptomatic patients if the serum PSA level is
< 20 ng/mL in the presence of well or moderately differentiated tumours.
In equivocal cases, 11C-choline-, 18F-flouridePET/CT or whole body MRI are an option.
Treatment of prostate cancer

An overview of the treatment options for patients with PCa,
subdivided by stage at diagnosis, is presented in Table 3. Due
to a lack of randomised controlled trials in PCa, one therapy
option cannot be considered superior to another. However,
based on the currently available literature, the recommendations presented in Table 3 can be made.
56 Prostate Cancer
Guidelines for the primary treatment of PCa

Stage
Treatment
T1a
Watchful
waiting
T1bT2b
Comment
Standard treatment for
Gleason score < 6 and 7 adenocarcinomas and < 10-year life
expectancy.
Active surveil- In patients with > 10-year life
lance
expectancy, re-staging with
TRUS and biopsy is recommended.
Radical pros- Optional in younger patients
with a long life expectancy,
tatectomy
especially for Gleason score
> 7 adenocarcinomas
Radiotherapy Optional in younger patients
with a long life expectancy,
in particular in poorly differentiated tumours. Higher
complication risks after TURP,
especially with interstitial
radiation.
Hormonal
Not an option.
Combination Not an option.
Active surveil- Treatment option in patients
with cT1c-cT2a, PSA
lance
< 10 ng/mL, biopsy Gleason
score < 6, < 2 biopsies positive, < 50% cancer involvement of each biopsy.
Patients with a life expectancy
< 10 years.
GR
B
A
C
B
Prostate Cancer 57
T1aT2c
Patients with a life expectancy > 10 years once they are

informed about the lack of
survival data beyond 10 years.
Patients who do not accept
treatment-related complications.
Radical pros- Optional in patients with pT1a A
tatectomy
PCa.
Standard treatment for
patients with a life expectancy
> 10 years who accept treatment-related complications.
Radiotherapy Patients with a life expectancy B
> 10 years who accept treatment-related complications.
Patients with contraindications for surgery.
Unfit patients with 5-10 years
of life expectancy and poorly
differentiated tumours (combination therapy is recommended; see below).
B
Brachytherapy Low-dose rate brachytherapy
can be considered for low risk
PCa patients with a prostate
volume < 50 mL and an IPSS
< 12.
58 Prostate Cancer
Hormonal
Combination
T3T4
Watchful
waiting
Radical prostatectomy
Symptomatic patients, who

need palliation of symptoms,
unfit for curative treatment.
Anti-androgens are associated
with a poorer outcome compared to active surveillance
and are not recommended.
For high-risk patients, neoadjuvant hormonal treatment
and concomitant hormonal
therapy plus radiotherapy
results in increased overall
survival.
Option in asymptomatic
patients with T3, well-differentiated and moderately-differentiated tumours, and a life
expectancy < 10 years who are
unfit for local treatment.
Optional for selected patients
with T3a, PSA < 20 ng/mL,
biopsy Gleason score < 8 and
a life expectancy > 10 years.
Patients have to be informed
that RP is associated with an
increased risk of positive surgical margins, unfavourable
histology and positive lymph
nodes and that, therefore,
adjuvant or salvage therapy
such as radiation therapy or
androgen deprivation might
be indicated.
Prostate Cancer 59
Radiotherapy
Hormonal
Combination
60 Prostate Cancer
T3 with > 5-10 years of life

expectancy. Dose escalation
of > 74 Gy seems to be of
benefit. A combination with
hormonal therapy can be recommended (see below).
Symptomatic patients, extensive T3-T4, high PSA level
(> 25-50 ng/mL), PSADoubling Time (DT) < 1 year.
Patient-driven, unfit patients.
Hormone monotherapy is not
an option for patients who are
fit enough for radiotherapy.
Overall survival is improved
by concomitant and adjuvant
hormonal therapy (3 years)
combined with external beam
radiation.
NHT plus radical prostatectomy: no indication.
N+,
M0
Watchful
waiting
Radiotherapy
Hormonal
Combination
M+
Watchful
waiting
Asymptomatic patients.
Patient-driven (PSA
<20-50ng/mL), PSA DT > 12
months. Requires very close
follow-up.
Optional for selected patients
with a life expectancy of > 10
years as part of a multimodal
treatment approach.
Optional in selected patients
with a life expectancy of > 10
years, combination therapy
with adjuvant androgen deprivation for 3 years is mandatory.
Standard adjuvant therapy in
more than 2 positive nodes to
radiation therapy or radical
prostatectomy as primary local
therapy. Hormonal therapy
should only be used as monotherapy in patients who are
unfit for any type of local
therapy.
No standard option.
Patient-driven.
No standard option. May have
worse survival/more complications than with immediate
hormonal therapy. Requires
very close follow-up.
Not a standard option.
B
B
Prostate Cancer
61
Radiotherapy
Hormonal
Not an option for curative

C
intent; therapeutic option in
combination with androgen
deprivation for treatment of
local cancer-derived symptoms.
Standard option. Mandatory in A
symptomatic patients.
For more detailed information and discussion on second-line

therapy, please see the full text version of the guidelines.
Follow-up of prostate cancer patients

Determination of serum PSA, disease-specific history and
DRE are the cornerstones in the follow-up of PCa patients.
Routine imaging procedures in stable patients are not recommended and should only be used in specific situations.
Guidelines for follow-up after treatment with

curative intent
GR
In asymptomatic patients, a disease-specific history

B
and a serum PSA measurement supplemented by DRE
are the recommended tests for routine follow-up.
These should be performed at 3, 6 and 12 months
after treatment, then every 6 months until 3 years, and
then annually.
After RP, a serum PSA level > 0.2 ng/mL can be asso- B
ciated with residual or recurrent disease.
After radiation therapy, a rising PSA level > 2 ng/mL
B
above the nadir PSA, rather than a specific threshold
value, is the most reliable sign of persistent or recurrent disease.
62 Prostate Cancer
Both a palpable nodule and a rising serum PSA level

can be signs of local disease recurrence.
Detection of local recurrence by TRUS and biopsy is
only recommended if it will affect the treatment plan.
In most cases TRUS and biopsy are not necessary
before second-line therapy.
Metastasis may be detected by pelvic CT/MRI or bone
scan. In asymptomatic patients, these examinations
may be omitted if the serum PSA level is < 20 ng/mL.
Routine bone scans and other imaging studies are not
recommended in asymptomatic patients. If a patient
has bone pain, a bone scan should be considered irrespective of the serum PSA level.
B
B
Guidelines for follow-up after hormonal treatment GR

Patients should first be evaluated at 3 and 6 months
after treatment initiation. Tests should at least include
serum PSA measurement, DRE, serum testosterone
and careful evaluation of symptoms in order to assess
the treatment response and side-effects.
If patients undergo intermittent androgen deprivation,
PSA and testosterone should be monitored at 3 month
intervals during the treatment pause.
Follow-up should be tailored to the individual patient,
according to symptoms, prognostic factors and the
treatment given.
In patients with stage M0 disease with a good treatment response, follow-up is scheduled every 6
months, and should include at least a disease-specific
history, DRE and serum PSA measurement.
Prostate Cancer 63
In patients with stage M1 disease with a good treatment response, follow-up is scheduled for every 3 to 6
months. Follow-up should include at least a diseasespecific history, DRE and serum PSA measurement,
frequently supplemented with haemoglobin, serum
creatinine and alkaline phosphatase measurements.
Patients (especially with M1b status) should be
advised about the clinical signs that could suggest spinal cord compression.
Where disease progression occurs, or if the patient
does not respond to the treatment given, follow-up
needs to be individualised.
Routine imaging of stable patients is not recommended.
Treatment of relapse after curative therapies

An effort should be made to distinguish between the probability of local failure only versus distant (+/- local) failure.
Initial pathology, how long after primary therapy the PSArelapse occurs and how fast the PSA-value is rising can all aid
in the distinction between local and distant failure. Poorly
differentiated tumour, early PSA-relapse and a short PSAdoubling time are all signs of distant failure. Treatment can
then be guided by the presumed site of failure, the patients
general condition and personal preferences. Imaging studies
are of limited value in patients with early PSA-relapse only.
64 Prostate Cancer
Guidelines for second-line therapy after curative

treatments
GR
B
Patients with presumed local failure
only may be candidates for salvage
radiotherapy. This should be given
with at least 64 Gy and preferably
before PSA has risen above
0.5 ng/mL. Other patients are best
offered a period of active surveillance
(active monitoring), with possible
hormonal therapy later on.
C
Selected patients may be candidates
Presumed
for salvage RP and they should be
local failure
informed about the high risk of comafter radioplications, such as incontinence and
therapy
erectile dysfunction.
Salvage prostatectomy should only be
performed in experienced centres.
Other patients are best offered a
period of active surveillance (active
monitoring), with possible hormonal
therapy later on.
Presumed dis- There is some evidence that early
B
tant failure
hormonal therapy may be of benefit
in +/- local failure, delaying progression, and possibly achieving a survival
benefit in comparison with delayed
therapy. The results are controversial.
Local therapy is not recommended
except for palliative reasons.
Presumed
local failure
after radical
prostatectomy
Prostate Cancer 65
Treatment of relapse after hormonal therapy

Castration-refractory PCa (CRPC) is usually a debilitating
disease, often affecting elderly patients. A multidisciplinary
approach is required with input from medical oncologists,
radiation oncologists, urologists, nurses, psychologists and
social workers. In most cases the decision whether to treat or
not is made based on counselling of the individual patient,
which limits the role of guidelines.
Guidelines for secondary hormonal management in GR

patients with CRPC
Anti-androgen therapy should be stopped once PSA
B
progression is documented.
No clear-cut recommendation can be made for the
C
most effective drug for secondary hormonal manipulations because data from randomised trials are scarce.
However, abiraterone and MDV3100 may address this
issue once final data from the prospective randomised
Phase III clinical trials are analysed.
Comment: An eventual anti-androgen withdrawal effect
should become apparent 4-6 weeks after the discontinuation
of flutamide or bicalutamide.
66 Prostate Cancer
Guidelines for cytotoxic therapy in patients with

CRPC
Patients with CRPC should be counselled, managed
and treated in a multidisciplinary team.
In non-metastatic CRPC, cytotoxic therapy should
only be used in a clinical trial setting.
In patients with a PSA rise only, two consecutive
increases of PSA serum levels above a previous reference level should be documented.
Prior to treatment, testosterone serum levels should be
below 32 ng/dL.
Prior to treatment, PSA serum levels should be
>2ng/mL to assure correct interpretation of therapeutic efficacy.
Potential benefits of cytotoxic therapy and expected
side-effects should be discussed with each individual
patient.
In patients with metastatic CRPC who are candidates
for cytotoxic therapy, docetaxel at 75 mg/m2 every 3
weeks is the drug of choice since it has shown a significant survival benefit.
In patients with symptomatic osseous metastases
due to CRPC, either docetaxel or mitoxantrone with
prednisone or hydrocortisone are viable therapeutic
options. If not contraindicated, docetaxel is the preferred agent based on the significant advantage in pain
relief.
In patients with relapse following first-line docetaxel
chemotherapy, based on the results of prospective
randomised clinical phase III trials, Cabazitaxel and
Abiraterone are regarded as first-choice option for
second-line treatment.
GR
B
B
B
B
Prostate Cancer 67
Second-line docetaxel may be considered in previously responding docetaxel-treated patients. Otherwise

treatment is to be tailored to the individual patients.
In case patients are not eligible for cabazitaxel or abiraterone, docetaxel is an option.
Guidelines for palliative management of patients

with CRPC
GR
Patients with symptomatic and extensive osseous

metastases cannot benefit from medical treatment
with regard to life prolongation.
Management of these patients has to be directed at
improving quality of life and providing pain reduction.
Effective medical management with the highest efficacy and a low frequency of side-effects is the major
goal of therapy.
Bisphosphonates (e.g. zoledronic acid) should be
offered to patients with skeletal masses to prevent
osseous complications. However, the benefits must be
balanced against the toxicity of these agents, in particular, jaw necrosis must be avoided.
Palliative treatments, such as radionuclides, external
beam radiotherapy and adequate use of analgesics,
should be considered early on in the management of
painful osseous metastases.
Spinal surgery or decompressive radiotherapy are
emergency surgeries which have to be considered for
patients with neurological symptoms thought to be
critical.
68 Prostate Cancer
Summary
Prostate cancer is a complex disease, in which many aspects
of the disease itself and the affected patient must be considered before decisions regarding diagnostic work-up, treatment and follow-up can be made.
Prostate Cancer 69
GUIDELINES ON RENAL CELL

CARCINOMA
(Text update April 2010)
B. Ljungberg (Chairman), N. Cowan, D.C. Hanbury,

M. Hora, M.A. Kuczyk, A.S. Merseburger, P.F.A. Mulders,
J-J. Patard, I.C. Sinescu
Eur Urol 2001 Sep;40(3):252-5
Eur Urol 2007 Jun;51(6):1502-10
Introduction
Renal cell carcinoma (RCC) represents 2-3% of all cancers,
with the highest incidence occurring in Western countries.
In Europe, until recently, there was a general annual increase
of 2% in the incidence. However, incidence rates of RCC
have now stabilised or declined in some countries (Sweden,
Denmark), while other European countries are still showing
an upward trend in the incidence of RCC.
The use of imaging techniques such as ultrasound (US) and
computed tomography (CT) has increased the detection of
asymptomatic RCC. In addition, during the last 10 years,
mortality rates have generally stabilised and declined prominently in some European countries. The peak incidence of
RCC occurs between 60 and 70 years of age, with a 1.5:1
ratio of men to women. Aetiological factors include lifestyle
factors, such as smoking, obesity, and hypertension. The
70 Renal Cell Carcinoma
most effective prophylaxis is to avoid cigarette smoking and

obesity.
Diagnosis and classification

More than 50% of RCCs are diagnosed incidentally.
Asymptomatic RCCs are generally smaller and of a lower
stage than symptomatic RCCs. In their natural clinical
course, RCCs remain asymptomatic and non-palpable until
late. The classic triad of flank pain, gross haematuria and
palpable abdominal mass is seldom found (6-10%). Clinical
symptoms include macroscopic haematuria, palpable mass,
arising varicocele, or bilateral lower extremity oedema; these
symptoms should initiate radiological examinations.
Paraneoplastic symptoms (e.g. hypertension, weight loss,
pyrexia, neuromyopathy, anaemia, polycythaemia, amyloidosis, elevated erythrocyte sedimentation rate, and abnormal liver function) are found in approximately 20-30% of
patients with RCC. About 20-30% of patients with symptoms
present as a result of metastatic disease.
Total renal function should always be evaluated. In patients
with any sign of impaired renal function, a renal scan and
total renal function evaluation should be undertaken to optimise the treatment decision.
Staging system
The current UICC 2009 TNM (Tumour Node Metastasis)
classification is recommended for the staging of RCC.
Renal Cell Carcinoma
71
Table 1: The 2009 TNM classification for RCC

T - Primary tumour
TX
T0
Tumour < 7 cm in greatest dimension, limited to the
T1
kidney
T1a Tumour < 4 cm in greatest dimension, limited
to the kidney
T1b Tumour > 4 cm but < 7 cm in greatest dimension
Tumour > 7 cm in greatest dimension, limited to the
T2
kidney
T2a Tumour > 7 cm in greatest dimension but
< 10 cm
T2b Tumours > 10 cm limited to the kidney
Tumour extends into major veins or perinephric tisT3
sues, but not into the ipsilateral adrenal gland and
not beyond Gerotas fascia
T3a Tumour grossly extends into the renal vein or
its segmental (muscle-containing) branches,
or tumour invades perirenal and/or renal sinus
(peripelvic) fat but not beyond Gerotas fascia
T3b Tumour grossly extends into the vena cava
below diaphragm
T3c Tumour grossly extends into vena cava or its
wall above the diaphragm or invades the wall
of the vena cava
T4
Tumour invades beyond Gerotas fascia (including
contiguous extension into the ipsilateral adrenal
gland)

N0
Metastasis in a single regional lymph node
N1
Metastasis in more than one regional lymph node
N2
Histopathological classification
Fuhrman nuclear grade is the most commonly used grading
system. The most aggressive pattern observed defines the
Fuhrman grade. RCC comprises four different subtypes with
genetic and histological differences: clear cell RCC (cRCC,
80-90%), papillary RCC (pRCC, 10-15%), chromophobe
RCC (chRCC, 4-5%), and collecting-duct carcinoma (1%).
Generally, the RCC types have different clinical courses and
responses to therapy.
Fuhrman grading and RCC subtype classification are recommended. There are several integrated prognostic systems
and nomograms that combine dependent prognostic factors,
which can be useful for predicting survival and differentiating follow-up. Molecular markers and gene expression
profiles appear promising for the prediction of survival, but
cannot be recommended yet in routine practice.
Other renal tumours

The common RCC types account for 85-90% of all renal
malignancies. The remaining 10-15% of renal tumours
Renal Cell Carcinoma 73
include a variety of uncommon carcinomas, a group of

unclassified carcinomas, and several benign kidney tumour
masses.
Except for angiomyolipomas, most of these less common renal tumours cannot be differentiated from RCC by
radiological imaging and should therefore be treated in
the same way as RCC.
Renal cysts with a Bosniak classification > III should be
surgically treated.
In oncocytomas verified on biopsy, follow-up can be considered as an option.
In angiomyolipomas, treatment (surgery, thermal ablation,
and selective arterial embolisation) can be considered
when the tumour > 4 cm. When possible, a nephronsparing procedure should be performed.
A standardised oncological programme does not exist for
advanced uncommon types of renal tumours.
Radiological investigations of RCC

Radiological investigations of RCC should include CT
imaging, before and after intravenous contrast to verify
the diagnosis and provide information on the function and
morphology of the contralateral kidney and assess tumour
extension, including extrarenal spread, venous involvement,
and enlargement of lymph nodes and adrenals. Abdominal
US and magnetic resonance imaging (MRI) are alternatives
to CT. Contrast-enhanced US can be helpful in specific cases.
Magnetic resonance imaging can be reserved for patients
with possible venous involvement, or allergy to intravenous
contrast. Chest CT is the most accurate chest staging; a routine chest x-ray should be done as a minimum. Renal masses
may be classified as solid or cystic by imaging criteria. For

evaluating solid renal masses, the presence of enhancement
is the most important criteria for differentiating malignant
lesions. For evaluating renal cystic masses, the Bosniak classification may be used.
Other diagnostic procedures (bone scan, MRI, brain CT)
should only be considered if indicated by clinical symptoms
or laboratory results in selected cases. Renal arteriography
and inferior venacavography have only a limited role in the
work-up of selected patients with kidney tumours. The true
value of positron emission tomography (PET) in the diagnosis and follow-up of RCC remains to be determined and is
currently not standard. In patients with any sign of impaired
renal function, an isotope renogram and total renal function
evaluation should be considered to evaluate the need to preserve renal function.
Renal biopsy
There is an increasing indication for biopsy of renal tumours,
as in ablative therapies and in patients being treated with
surveillance or systemic therapy without previous histopathology. Core biopsy has demonstrated a high specificity and
sensitivity for determining eventual malignancy, but about
20% of biopsies are non-conclusive. Percutaneous biopsy is
rarely required for large renal masses scheduled for nephrectomy since it will not alter management. Fine-needle biopsy
has only a limited role in the clinical work-up of patients
with renal masses.
Guidelines for the primary treatment of RCC

Until recently, the standard for curative therapy of RCC was
radical nephrectomy with complete removal of the tumourbearing kidney with perirenal fat and Gerotas fascia.
For localised RCCs, nephron-sparing surgery is recommended. Radical nephrectomy is recommended for patients
with localised RCC, who are not suitable for nephron-sparing
surgery due to locally advanced tumour growth, when partial
resection is technically not feasible due to an unfavourable
localisation of the tumour, or when the patients general
health has significantly deteriorated. Complete resection
of the primary RCC either by open or laparoscopic surgery
offers a reasonable chance for cure.
If pre-operative imaging is normal, routine adrenalectomy
is not indicated. Lymphadenectomy should be restricted
Table 2: 2010 recommendations for primary surgical

treatment of RCC according to T-stage
Stage
T1
Surgery
Nephron-sparing surgery
Radical nephrectomy
T2
Radical nephrectomy
T3,T4
Radical nephrectomy
Open
Laparoscopic
Laparoscopic
Open
Laparoscopic
Open
Open
Laparoscopic
to staging because extended lymphadenectomy does not

improve survival. In patients who have RCCs with tumour
thrombus and no metastatic spread, prognosis is improved
after nephrectomy and complete thrombectomy.
Embolisation of the primary tumour is indicated in patients
with gross haematuria or local symptoms (e.g. pain), in
patients unfit for surgical intervention, and before surgical
resection of large skeletal metastases. No benefit is associated
with tumour embolisation before routine radical nephrectomy.
Absolute indications for partial nephrectomy are anatomical or functional solitary kidney or bilateral RCC. Relative
indications are a functioning opposite kidney affected by a
condition that might impair renal function and hereditary
Recommendations
Recommended standard
Optional in experienced centres
In patients not suitable for nephron-sparing surgery
Optional in patients not suitable for nephron-sparing
surgery
Adequate and recommended, but carries a higher morbidity
Feasible in selected patients in experienced centres
Feasible in selected patients
Renal Cell Carcinoma
77
forms of RCC with a high risk of developing a tumour in the

contralateral kidney.
Localised unilateral RCC with a healthy contralateral kidney
is an indication for elective surgery.
Nephron-sparing surgery is recommended for patients with
localised RCC, as recurrence-free and long-term survival
rates are similar to those for radical nephrectomy. Even in
selected patients with a tumour diameter of up to 7 cm,
nephron-sparing surgery has achieved results equivalent
to those of a radical approach. If the tumour is completely
resected, the thickness of the surgical margin (> 1 mm)
does not correlate with the likelihood of local recurrence. If
RCCs of larger size are treated with nephron-sparing surgery,
follow-up should be intensified, as there is an increased risk
of intrarenal recurrences.
Laparoscopic radical and partial nephrectomy
Laparoscopic radical nephrectomy has a lower morbidity
compared with open surgery. It has become an established
surgical procedure for RCC. Whether done retro- or transperitoneally, the laparoscopic approach must duplicate
established, open surgical, oncological principles. Long-term
outcome data indicate equivalent cancer-free survival rates
versus open radical nephrectomy. Thus, laparoscopic radical nephrectomy is now considered the standard of care for
patients with T1 and T2 RCCs, who are not treatable by
nephron-sparing surgery. Laparoscopic radical nephrectomy
should not be performed in patients with T1 tumours for
whom partial resection is indicated. Laparoscopic nephrectomy is expected to become a widely available treatment option
and should be promoted in centres treating RCC.

In experienced hands, partial laparoscopic nephrectomy may
be an alternative to open nephron-sparing surgery in selected
patients. The optimal indication for laparoscopic nephronsparing surgery is a relatively small and peripheral tumour.
Laparoscopic partial resection has a longer intra-operative
ischaemia time than open partial nephrectomy and therefore
carries a higher risk for reduced long-term renal function. It
also has a higher surgical complication than open surgery.
However, the oncological outcome seems comparable in
available series. Robotic-assisted partial nephrectomy has
been introduced, but requires further evaluation and more
mature data before any conclusive recommendations can be
made.
Conclusion: Radical nephrectomy, preferably laparoscopic, is
recommended for patients with localised RCC, who are not
suitable for nephron-sparing surgery. Open partial nephronsparing surgery remains the standard of care. Laparoscopic
partial nephrectomy should be limited to experienced centres.
Minimally invasive alternative treatment
Minimally invasive techniques, such as ablation with percutaneous radio-frequency, cryotherapy, microwave, and
high-intensity focused US (HIFU), are suggested alternatives
to surgery. Potential advantages of these techniques include
reduced morbidity, outpatient therapy, and the ability to treat
high-risk patients not fit for conventional surgery.
These experimental treatments might be recommended for
selected patients with small, incidentally found, renal cortical

lesions, elderly patients, patients with a genetic predisposition to multiple tumours, patients with a solitary kidney,
or patients with bilateral tumours. The oncological efficacy
remains to be determined for both cryotherapy and radiofrequency ablation (RFA), which are the most often used
minimally invasive techniques. Current data suggest that cryoablation, when performed laparoscopically, results in fewer
re-treatments and improved local tumour control compared
with RFA. For both treatments, tumour recurrence rates are
higher compared with nephron-sparing surgery. Further
research is needed to determine the oncological success rate
and complications associated with these procedures.
Adjuvant therapy
Adjuvant tumour vaccination may improve the duration
of the progression-free survival (PFS), which is especially
important in patients at high risk of metastases, e.g. T3 RCC.
Cytokine therapy does not improve survival after nephrectomy. Although there is no current data supporting adjuvant
therapy with targeting agents, three worldwide phase III randomised trials are ongoing. Outside controlled clinical trials,
there is no indication for adjuvant therapy following surgery.
Surgical treatment of metastatic RCC (mRCC)
Nephrectomy of the primary tumour is curative only if surgery can excise all tumour deposits. For most patients with
mRCC, nephrectomy is only palliative. In a meta-analysis of
two randomised studies, comparing nephrectomy + immunotherapy versus immunotherapy alone, increased longterm survival was found in patients who underwent prior
nephrectomy. In patients with a good performance status

(PS), tumour nephrectomy + interferon-alpha (IFN-) can
be recommended. For targeting agents, there is no current
knowledge whether cytoreductive surgery is advocated before
or after successful medical therapy. However, in the absence
of available evidence data, cytoreductive nephrectomy is recommended when possible.
Complete removal of metastases contributes to improved
clinical prognosis. Metastasectomy should be carried out in
patients with resectable disease and a good PS. It should also
be considered in patients with residual and respectable metastatic lesions, who have previously responded to systemic
therapy.
Radiotherapy for metastases
For selected patients with non-resectable brain or osseous
lesions, radiotherapy can induce significant symptom relief.
Systemic therapy for mRCC

Chemotherapy
Chemotherapy is considered ineffective in patients with
RCC.
Immunotherapy
Available data show that immunotherapy with IFN- is
beneficial in only a limited subset of patients; those with
good PS, a PFS of > 1 year following initial diagnosis, and
preferably the lung as the sole metastatic site. Randomised
studies comparing targeting agents in a first-line setting to
IFN- monotherapy have demonstrated superiority for either
sunitinib, bevacizumab + IFN-, or temsirolimus. IFN-

monotherapy only remains an option in selected patients as
first-line therapy for mRCC. High-dose bolus interleukin-2
(IL-2) gives durable complete responses in a limited number
of patients; however, the toxicity associated with IL-2 is substantially higher than that with IFN-. To date, no superiority has been shown for treatment with either IFN- or IL-2
in mRCC patients. Only patients with cRCC benefit clinically
from immunotherapy.
A combination of cytokines, with or without additional
chemotherapy, does not improve overall survival compared
with monotherapy.
The MSKCC (Motzer) prognostic criteria can be used for risk
stratification including; Karnowsky performance status
(< 80), time from diagnosis to treatment with IFN- (< 12
months), Haemoglobin (< normal), Lactate dehydrogenase
(> 1.5 upper normal limit) and corrected serum calcium
(> normal). Low risk, 0 risk factor; intermediate, 1-2 risk factors; high risk > 3 risk factors.
Angiogenesis inhibitor drugs
Recent advances in molecular biology have led to the development of several novel agents for the treatment of mRCC.
In sporadic and VHL (von Hippel Lindau) cRCC, the accumulation of hypoxia inducible factor (HIF) due to a defective
VHL protein results in over-expression of vascular endothelial growth factor (VEGF) and platelet-derived growth
factor (PDGF), promoting neo-angiogenesis. This process
substantially contributes to the development and progression
Table 3: Recommendations for first and second line

systemic therapy in mRCC
Treatment
First-line
Second-line
Risk or prior
treatment
Low- or intermediate-risk mRCC
High-risk mRCC
Prior cytokine
therapy
Prior VEGFR
therapy
Prior mTOR inhibitor therapy
Recommended
agent
Sunitinib
Bevacizumab +
IFN-a
Pazopanib
Temsirolimus
Sorafenib
Pazopanib
Everolimus
Clinical trials
of RCC. At present, four targeting drugs have been approved

both in the USA and in Europe for mRCC, while other agents
have shown significant efficacy in randomised controlled trials.
Tyrosine kinase inhibitors (TKIs)
Several TKIs have shown efficacy in cRCC with increased
PFS as both first- and second-line treatments of mRCC.
Sorafenib is an oral multikinase inhibitor with proven
increased PFS as a second-line treatment after failure of
systemic immunotherapy.
Sunitinib is an oral TKI. In a phase III first-line study
comparing sunitinib with IFN-, sunitinib achieved a
longer PFS time (11 months vs. 5 months) in low- and
intermediate-risk patients. In patients who did not receive
any post-study treatment, overall survival was longer in

the sunitinib-only treated group than in the IFN- treated
only group (28.1 months vs. 14.1 months, respectively).
Pazopanib is an oral TKI targeting VEGF and PDGF
receptors and c-Kit. In a prospective randomised trial
of pazopanib versus placebo in treatment-naive mRCC
patients and cytokine-treated patients, there was a significant improvement in PFS from 4.2 to 9.2 months and
tumour response was observed.
VEGF antibodies
Bevacizumab is a humanised monoclonal antibody that
binds VEGF. A double-blind phase III trial showed a
median 31% overall response with bevacizumab + IFN-
versus 13% in IFN- monotherapy. Median PFS increased
significantly from 5.4 months with IFN- to 10.2 months
for bevacizumab + IFN-, but was restricted to low- and
intermediate-risk patients.
Mammalian target of rapamycin (mTOR) inhibitors
These inhibitors, which affect the mTOR pathway, show significant efficacy in mRCC, in other RCC types besides cRCC,
and also in high-risk patients.
Temsirolimus is a specific inhibitor of mammalian target
of rapamycin. A phase III trial demonstrated increased
overall survival in poor-risk patients with mRCC given
temsirolimus monotherapy compared with IFN-.
Everolimus is an oral mTOR inhibitor. A recent phase III
study in patients who had failed previous anti-VEGF-R
treatment showed a PFS of 4 months with everolimus versus 1.9 months with placebo.
Clinical research continues into the use of these and several

other new novel agents for the primary or secondary treatment of mRCC, including monotherapy, in combination
with each other or with cytokines, or in the adjuvant setting. Only limited overall survival data are available for these
new agents and their role is still under development. In the
sunitinib randomised trial, patients crossed over from IFN-
to sunitinib (n = 25), the median survival times were 20.0
versus 26.4 months for sunitinib, respectively (p = 0.03). In
patients who did not receive any post-study sunitinib, the
median overall survival was 14.1 months versus 28.1 months
in the sunitinib group. To date, there has been no data on
the curative effect of the new agents. These agents appear to
promise to stabilise mRCC for a prolonged period of time.
However, their clinical use has to be balanced against their
toxicity profile and the patients quality of life.
Recommendations for systemic therapy

Tyrosine kinase inhibitors should be considered as first- or
second-line treatment for mRCC patients as shown in Table
3. Interferon- monotherapy only remains as an option in
selected patients as first-line therapy for mRCC.
Surveillance following surgery for RCC

Surveillance following surgery for RCC allows the urologist
to monitor post-operative complications, renal function, local
recurrence after partial nephrectomy or ablative treatment,
recurrence in the contralateral kidney, and development of
metastases.
The method and timing of investigation has been the subject

of many publications. Using different scoring systems and
algorithms, patients can be categorised as at low-, intermediate- or high-risk of developing metastases. Despite extensive
research, there is no general recommendation for the method
and timing of investigations for surveillance. In fact, there
is no evidence for whether early versus later diagnosis of
recurrence improves survival. However, follow-up remains
important to increase knowledge of the disease and should
be performed by the urologist, who should record the time
elapsed to recurrence or metastatic development. Follow-up
also allows metastases to be identified early.
Early identification of metastases increases the possibility
of surgical resection and efficacy of systemic treatment at a
time when the tumour burden is as low as possible. This is
particularly important with ablative therapies, such as cryotherapy and RFA, where the local recurrence rate is higher
than conventional surgery and the patient may still be cured
by repeat ablative therapy or radical nephrectomy. In metastatic disease, more extended tumour growth can reduce
the possibility of surgical resection, which is considered the
standard therapy in cases of resectable and preferably solitary
lesions. In addition, within clinical trials, an early diagnosis
of tumour recurrence might enhance the efficacy of a systemic treatment if the tumour burden is low.
The urologist can therefore be selective in the use of imaging
and the need for intensive surveillance. Although there is no
evidence-based standard for the follow-up of patients with
RCC, there are several scoring systems and nomograms for
predicting tumour recurrence and metastases. Using these

nomograms, several stage-based surveillance regimes have
been proposed. However, none include ablative therapies.
There is therefore a need for a surveillance algorithm that
monitors patients after treatment for RCC that recognises not
only the patients risk profile but also treatment efficacy. An
example is given in Table 4; please note this is not an EAU
recommendation.
For patients with metastatic disease, an individual followup plan is required.
Table 4: Example of a proposed follow-up algorithm

for surveillance after treatment for RCC with
combined patient risk profile and treatment
efficacy
(This is an example of a follow-up scheme; GR: C)
Treatment
Risk profile
and schedule Low
Intermediate High
Treatment
RN/PN only RN/PN/cryo/ RN/PN/cryo/
RFA
RFA
6 months
CXR and US CT
CT
1 year
CXR and US CXR and US CT
2 years
CXR and US CT
CT
3 years
4 years
5 years
CXR and US CT
CT
> 5 yrs
Discharge
Yearly CXR
CXR/CT in
and US
alternate
years
CT = computed tomography of chest and abdomen;

cryo = cryotherapy; CXR = chest x-ray; PN = partial nephrectomy; RFA = radio-frequency ablation; RN = radical nephrectomy;
US = ultrasound of kidneys and renal bed.
GUIDELINES ON PENILE CANCER

G. Pizzocaro, F. Algaba, S. Horenblas, E. Solsona, S. Tana,

H. Van Der Poel, N. Watkin
Eur Urol 2010 Jun;57(6):1002-12
Introduction
Over recent years, the cure rate for penile cancer has risen to
80% because of improved knowledge of the disease, earlier
diagnosis, technological advances, and specialist treatment in
centres of excellence.
In Western countries, primary malignant penile cancer is
uncommon, with an overall incidence of less than 1.00 per
100,000 males in Europe and the United States of America
(USA). Incidence also varies according to racial group, ethnicity, and geographical location. Social and cultural habits,
hygienic and religious practices interfere significantly with
risk factors.
Since a few years, there has been a well-documented association between human papillomavirus (HPV) and squamous
cell carcinoma (SCC). Vaccination is available for very young
females against HPV strains responsible for most cases of cervical cancer. Vaccination will be considered in males according to the results in females.
Penile Cancer 89
Classification and pathology

The new, 2009, Tumor Node Metastasis (TNM) classification for penile cancer includes a change for the T1 category
(Table 1). This classification needs a further update for the
definition of the T2 category*.
Table 1: 2009 TNM staging classification

T - Primary tumour
TX
T0
Carcinoma in situ
Tis
Non-invasive verrucous carcinoma, not associated
Ta
with destructive invasion
T1
T1a without lymphovascular invasion and well or
moderately differentiated (T1G1-2)
T1b with lymphovascular invasion or poorly differentiated / undifferentiated (T1G3-4)
T2* Tumour invades corpus spongiosum/corpora
cavernosa
Tumour invades urethra
T3
Tumour invades other adjacent structures
T4
No palpable or visibly enlarged inguinal lymph node
N0
Palpable mobile unilateral inguinal lymph node
N1
Palpable mobile multiple or bilateral inguinal lymph
N2
nodes
Fixed inguinal nodal mass or pelvic lymphadenopaN3
thy, unilateral or bilateral
90 Penile Cancer
TNM pathological classification
The pT categories correspond to the T categories. The pN
categories are based upon biopsy, or surgical excision.
Table 2: 2009 TNM pathological classification

pN - Regional lymph nodes
pNX Regional lymph nodes cannot be assessed
pN0 No regional lymph node metastasis
pN1 Intranodal metastasis in a single inguinal lymph
node
pN2 Metastasis in multiple or bilateral inguinal lymph
nodes
pN3 Metastasis in pelvic lymph node(s), unilateral or
bilateral or extranodal extension of regional lymph
node metastasis
pM - Distant metastasis
pM0 No distant metastasis
pM1 Distant metastasis
G - Histopathological grading
Grade of differentiation cannot be assessed
Gx
Well differentiated
G1
Moderately differentiated
G2
G3-4 Poorly differentiated/undifferentiated
Pathology
Squamous cell carcinoma accounts for more than 95% of
cases of malignant penile disease. Table 3 lists premalignant
Penile Cancer
91
lesions and Table 4 lists the different types of penile SCC

neoplasia.
Table 3: Premalignant lesions

Lesions sporadically associated with SCC of the penis
Cutaneous horn of the penis
Bowenoid papulosis of the penis
Lesion at intermediate risk
Balanitis xerotica obliterans (lichen sclerosus et atrophicus)
Lesions at high risk of developing SCC of the penis (up to
one-third transform to invasive SCC)
Penile intraepithelial neoplasia (carcinoma in situ)
Erythroplasia of Queyrat and Bowens disease
Table 4: Pathologic classification of SCC of the penis

Types of SCC
Classic
Basaloid
Verrucous and its varieties: warty (condylomatous)
carcinoma; verrucous carcinoma; papillary carcinoma;
hybrid verrucous carcinoma; and mixed carcinomas
(warty basaloid, adenobasaloid carcinoma)
Sarcomatoid
Adenosquamous
Growth patterns of SCC
Superficial spread
Nodular or vertical-phase growth
Verrucous
92 Penile Cancer
Differentiation grading systems for SCC

Broders grading system
Maiches system score
Diagnosis
Accurate histological diagnosis and staging of both the primary tumour and regional nodes are a prerequisite before
making treatment decisions (Table 5).
Biopsy
The need for histological confirmation is dependent on:
doubt about the exact nature of the lesion;
treatment of the lymph nodes based on pre-operative histology.
In these cases an adequate biopsy is advised. Although a
punch biopsy may be sufficient for superficial lesions, but an
excisional one is preferred. There is no need for biopsy if:
there is no doubt about the diagnosis;
treatment of the lymph nodes is postponed after treatment
of the primary tumour and/or after histological examinations of the sentinel node(s).
Physical examination
The physical examination of suspected penile cancer must
record:
diameter of the penile lesion(s) or suspicious areas;
location of lesion(s) on the penis;
number of lesions;
morphology of lesion(s): papillary, nodular, ulcerous or
flat;
relationship of lesion(s) to other structures, e.g. submuPenile Cancer 93
cosa, tunica albuginea, urethra, corpus spongiosum and

corpus cavernosum;
colour and boundaries of lesion(s);
penile length.
Imaging
Physical examination is reliable in determining infiltration
into the corpora. If doubt exists on depth of infiltration or
proximal extension, magnetic resonance imaging (MRI) may
be helpful on erect penis ( prostaglandin E1 injection).
Table 5: Guidelines for the diagnosis of penile

cancer
GR
Primary tumour
C
Physical examination, recording morphological and
physical characteristics of the lesion.
Cytological and/or histological diagnosis.
C
Inguinal lymph nodes
Physical examination of both groins, recording
nodal morphological and physical characteristics.
If nodes are non-palpable, DSNB is indicated; if
DSNB not available, ultrasound-guided FNAC/risk
factors.
If nodes are palpable, FNAC for cytological diagnosis.
C
Regional metastases (inguinal and pelvic nodes)
A pelvic CT scan/PET-CT scan is indicated in
patients with metastatic inguinal nodes.
94 Penile Cancer
C
Distant metastases (beside inguinal and pelvic
nodes)
PET-CT scan also allows evidence of distant
metastasis.
If PET-CT is not available, abdominal CT scan and
chest X-ray are advisable, and in symptomatic M1
patients a bone scan is also advisable.
C
Biological laboratory determinations for penile
cancer are investigational and not for clinical use.
CT = computed tomography; DNSB = dynamic sentinel node
biopsy; GR = grade of recommendation; FNAC = fine-needle
aspiration cytology; PET = positron emission tomography.
Treatment
The primary tumour and regional lymph nodes are usually
treated separately (Table 6). Correct staging is crucial for
accurate treatment. Lymphadenectomy (LAD) is mandatory
for patients with evidence of inguinal lymph node metastases.
Table 6: Guidance on treatment strategies for penile

cancer
Primary tumour Conservative treatment is to
be considered whenever
possible
LE
GR
Penile Cancer 95
Category Tis,
Ta, T1a (G1,
G2)
Categories: T1b
(G3) and T2
(glans only)
Category T2
(invasion of the
corpora)
Category T3
invasion of urethra
Category T4
(other adj. structures)
Local disease
recurrence after
conservative
therapy
Radiotherapy
96 Penile Cancer
CO2 or Nd:YAG laser surgery,

wide local excision, glans
resurfacing, or glans resection,
depending on size and location of the tumour
Mohs micrographic surgery
or photodynamic therapy for
well differentiated superficial
lesions (Tis, G1, Ta)
Glansectomy, with or without
tips amputation or reconstruction
Partial amputation
2b
2b
2b
Total amputation with perineal urethrostomy
2b
Eligible patients: neoadjuvant

chemotherapy followed by
surgery in responders.
Alternative: external radiation
Salvage surgery, consisting
of penis-sparing treatment in
small recurrences
Larger recurrence: some form
of amputation
Organ-preserving treatment
in selected patients with Tl-2
of glans or coronal sulcus,
lesions < 4 cm
2b
2b
Chemotherapy
Neo adjuvant, before surgery 3

C
Palliation in advanced or
3
C
metastatic disease
CO2 = carbon dioxide; Nd:YAG = neodymium:yttrium-aluminum-garnet.
Table 7: Guidance on treatment strategies for regional

lymph nodes in penile cancer
Regional lymph
nodes
No palpable
inguinal
nodes
Palpable
inguinal nodes
Management of regional
lymph nodes is fundamental
Tis, Ta G1, T1G1: surveillance
> T1G2: DSNB
(NB: Inguinal LAD if histology
is positive)
If DSNB not available: risk
factors / nomogram decisionmaking
Ultrasound-guided FNAB
(DSNB is unsuitable for palpable nodes)
Negative biopsy: surveillance
(repeat biopsy)
Positive biopsy: inguinal LAD
on positive side
(NB: Modified LAD must
include the central zone and
both superior Daselers zones)
LE
GR
2a
2a
B
B
2a
Penile Cancer 97
Pelvic nodes
Adjuvant
chemotherapy
Patients with
fixed or
relapsed
inguinal nodes
98 Penile Cancer
Pelvic LAD if there is: extranodal metastasis; Cloquet node

involved; > 2 inguinal node
metastases
Unilateral pelvic LAD if unilateral lymph node metastases
with prolonged inguinal incision
Bilateral pelvic LAD if bilateral
inguinal metastases
In patients with > 1 intranodal metastasis (pN2 pN3)
after radical LAD, survival is
improved by adjuvant chemotherapy (3 courses of cisplatin,
fluorouracil [PF] chemotherapy)
Neo-adjuvant chemotherapy
is strongly recommended in
patients with unresectable or
recurrent lymph node metastases
Taxanes seem to improve the
efficacy of standard PF chemotherapy (or carboplatin)
2a
2b
2a
2b
2a
Curative radiotherapy may be 2a B

used for palliation in primary
tumours of the glans penis
and sulcus < 4 cm or
2a B
Prophylactic radiotherapy
in clinical N0 patients is not
indicated
LAD = lymphadenectomy; FNAB = fine-needle aspiration biopsy;
DSNB = sentinel node biopsy.
Radiotherapy
Follow-up
The aim of follow-up is to detect local and/or regional recurrences at an early curable stage. Metastases at distant sites are
fatal. Risk stratification for recurrence is helpful. Traditional
follow-up methods have been inspection and physical evaluation.
Modern ultrasound or PET-CT imaging is a useful
adjunct. The follow-up interval and strategies for patients
with penile cancer are guided by the initial treatment of the
primary lesion and regional lymph nodes (Table 7). About
92% of all recurrences occur within 5 years and they may
be neo-occurrences. Follow-up can stop after 5 years in well
educated and motivated patients able to perform self-examination.
Penile Cancer 99
Table 8: Follow-up schedule for penile cancer

Interval of follow-up
Years 1 and 2
Years 3, 4 and 5
Recommendations for follow-up of the primary tumour
Penile preserving treat- 3 months
6 months
ment
Amputation
6 months
1 year
Recommendations for follow-up of the inguinal lymph nodes
Wait-and-see
3 months
6 months
pN0
6 months
1 year
pN+
3 months
6 months
Quality of life
As more people achieve long-term survival after cancer, sexual
dysfunction and infertility are increasingly recognised as
negative consequences. Penile-sparing surgery allows a better
quality of life than penectomy and must be considered whenever feasible. Psychological support should be offered at a low
threshold.
100 Penile Cancer
Examinations and
investigations
Maximum duration
of follow-up
GR
Regular physician or selfexamination

5 years
5 years
5 years
5 years
5 years

Ultrasound with FNAB
Ultrasound with FNAB
Penile Cancer 101
Guidelines on Testicular Cancer

(Limited text update March 2011)
P. Albers (chairman), W. Albrecht, F. Algaba, C. Bokemeyer,

G. Cohn-Cedermark, K. Fizazi, A. Horwich, M.P. Laguna
Eur Urol 2008;53(3):478-96,497-513
Introduction
Compared with other types of cancer, testicular cancer is
relatively rare accounting for approximately 1-1.5% of all
cancers in men.
A steady increase in incidence has been seen over the past
decades in the industrialised countries. The majority of these
tumours are derived from germ cells (seminoma and nonseminoma germ cell testicular cancer) and more than 70% of
patients are diagnosed with stage I disease. Epidemiological
risk factors for testicular cancer as well as pathological and
clinical risk factors in stage I and in metastatic disease are
well established. Nowadays testicular tumours show excellent cure rates, mainly due to early diagnosis and their
extreme chemo- and radiosensitivity.
Table 1: Prognostic risk factors for the development of

tumours
Epidemiological risk factors
History of cryptorchidism
Klinefelters syndrome
102 Testicular Cancer
Familial history of testis cancer in first-grade relatives

Presence of contralateral tumour
Tin or infertility
Pathological prognostic risk factors for occult metastatic
disease (for stage I)
For seminoma
- Tumour size (> 4 cm)
- Invasion of the rete testis
For non-seminoma
- Vascular/lymphatic invasion or peri-tumoural invasion
- Proliferation rate (MIB-1) > 70%
- Percentage embryonal carcinoma > 50%
Clinical (for metastatic disease)
Primary location
Elevation of tumour marker levels
Presence of non-pulmonary visceral metastasis
Classification
Testicular epithelial cancer is classified into three categories:
(a) germ cell tumours;
(b) sex cord stromal tumours;
(c) miscellaneous germ cell/sex cord stromal tumours.
Germ cell tumours account for 90-95% of cases of testicular
cancer according to the WHO classification system.
Testicular Cancer 103
Table 2: The recommended pathological classification

(modified World Health Organization 2004)
1. Germ cell tumours
Intratubular germ cell neoplasia
Seminoma (including cases with syncytiotrophoblastic
cells)
Spermatocytic seminoma (mention if there is a sarcomatous
component)
Embryonal carcinoma
Yolk sac tumour
Choriocarcinoma
Teratoma (mature, immature, with malignant component)
Tumours with more than one histological type
(specify % of individual components)
2. Sex cord/gonadal stromal tumours
Leydig cell tumour
Malignant Leydig cell tumour
Sertoli cell tumour (lipid-rich variant, sclerosing, large cell
calcifying)
Malignant Sertoli cell tumour
Granulosa (adult and juvenile)
Thecoma/fibroma group of tumours
Other sex cord/gonadal stromal tumours (incompletely differentiated, mixed)
Tumours containing germ cell and sex cord/gonadal stromal (gonadoblastoma)
3. Miscellaneous non-specific stromal tumours
Ovarian epithelial tumours
Tumours of the collecting ducts and rete testis
Tumours (benign and malignant) of non-specific stroma
Diagnosis of testicular cancer

The diagnosis of testicular cancer is based on:
Clinical examination of the testis and general examination to
rule out enlarged nodes or abdominal masses.
Ultrasound of the testis to confirm testicular mass and always
in a young man with a retroperitoneal mass or elevated
tumour serum markers and without a palpable scrotal mass.
Currently, testicular ultrasound should be performed even in
the presence of clinically evident tumour.
Serum tumour markers before orchiectomy (AFP and hCG)
and LDH. The latter is mandatory in advanced tumours.
Inguinal exploration and orchiectomy with en bloc removal of
testis, tunica albuginea, and spermatic cord. If the diagnosis
is not clear, a testicular biopsy (tumour enucleation) is to be
taken for histopathological frozen section.
Organ-sparing surgery can be attempted in special cases
(bilateral tumour or solitary testes). Routine contralateral
biopsy for diagnosis of carcinoma in situ should be discussed
with the patient and is recommended in high risk patients
(testicular volume < 12 mL, a history of cryptorchidism and
age under 40 years).
Diagnosis and treatment of Tin

Although the diagnosis of Tin remains controversial, a biopsy
should be offered to patients with high risk for contralateral
Tin (testicular volume < 12 mL, history of cryptorchidism
or poor spermatogenesis). If performed, a double biopsy is
preferred. In case of Tin, local radiotherapy is the treatment
after counselling on impaired testosterone production and
infertility.
Staging of testicular tumours

For an accurate staging the following steps are necessary:
Postorchiectomy half-life kinetics of serum tumour markers.
The persistence of elevated serum tumour markers 3 weeks
after orchiectomy may indicate the presence of disease,
while its normalisation does not necessarily mean absence of
tumour. Tumour markers should be assessed until they are
normal, as long as they follow their half-life kinetics and no
metastases are revealed.
Assessment of retroperitoneal and mediastinal nodes and viscera.
(Abdominopelvic CT scan and thoracic CT scan/X-ray
Thorax) and supraclavicular nodes (physical examination).
MRI is helpful only when the above are inconclusive or in
patients with an allergy to contrast agents. Other examinations such as brain or spinal CT, bone scan or liver ultrasound should be performed if metastases are suspected.
In patients diagnosed with testicular seminoma and a positive
abdominopelvic CT scan, a chest CT scan is recommended.
A chest CT scan should be routinely performed in patients
diagnosed with non-seminomatous germ cell tumours

(NSGCT) because in up to 10% of cases, small subpleural
nodes may be present that are not visible radiologically.
Staging system
The Tumour, Node, Metastasis (TNM 2009) staging system
is endorsed.
Table 3: TNM classification for testicular cancer

pT - Primary tumour1
pTX Primary tumour cannot be assessed
pT0 No evidence of primary tumour (e.g. histologic scar
in testis)
pTis Intratubular germ cell neoplasia (testicular intraepithelial neoplasia)
pT1 Tumour limited to testis and epididymis without
vascular/lymphatic invasion: tumour may invade
tunica albuginea but not tunica vaginalis
pT2 Tumour limited to testis and epididymis with vascular/lymphatic invasion, or tumour extending through
tunica albuginea with involvement of tunica vaginalis
pT3 Tumour invades spermatic cord with or without vascular/lymphatic invasion
pT4 Tumour invades scrotum with or without vascular/
lymphatic invasion
N - Regional lymph nodes clinical
N0
Metastasis with a lymph node mass < 2 cm in greatest dimension, or multiple lymph nodes, none > 2
cm in greatest dimension
Metastasis with a lymph node mass > 2 cm but < 5
N2
cm in greatest dimension, or multiple lymph nodes,
any one mass > 2 cm but < 5 cm in greatest dimension
Metastasis with a lymph node mass > 5 cm in greatN3
est dimension
pN - Pathological regional lymph nodes
pNX Regional lymph nodes cannot be assessed
pN0 No regional lymph node metastasis
pN1 Metastasis with a lymph node mass < 2 cm in greatest dimension and 5 or fewer positive nodes, none >
2 cm in greatest dimension
pN2 Metastasis with a lymph node mass > 2 cm but <
5 cm in greatest dimension; or > 5 nodes positive,
none > 5 cm; or evidence of extranodal extension of
tumour
pN3 Metastasis with a lymph node mass > 5 cm in greatest dimension
MX Distant metastasis cannot be assessed
M1a Non-regional lymph node(s) or lung
M1b Other sites
pM - Pathological distant metastasis
The pM category corresponds to the M category
N1
S - Serum tumour markers

Sx
Serum markers studies not available or not performed
Serum marker study levels within normal limits
S0
S1
S2
S3
LDH (U/L)
< 1.5 x N and
1.5-10 x N or
> 10 x N or
hCG (mlU/ml)
< 5,000 and
5,000-50,000 or
> 50,000 or
AFP (ng/ml)
< 1,000
1,000-10,000
> 10,000
Except for pTis and pT4, where radical orchiectomy is not

always necessary for classification purposes, the extent of the
primary tumour is classified after radical orchiectomy; see pT.
In other circumstances, TX is used if no radical orchiectomy has
been performed.
The International Germ Cell Cancer Collaborative Group
(IGCCCG) defined a prognostic factor-based staging system
for metastatic germ cell cancer that includes good and intermediate prognosis seminoma and good, intermediate, and
poor prognosis NSGCT.
Table 4: Prognostic-based staging system for

metastatic germ cell cancer (IGCCCG)
Good-prognosis group
Non-seminoma (56% of
cases)
5-year PFS 89%
5-year survival 92%
All of the following criteria:
Testis/retroperitoneal primary
No non-pulmonary visceral
metastases
AFP < 1,000 ng/mL
hCG < 5,000 IU/L (1,000 ng/mL)
LDH < 1.5 x ULN
Seminoma (90% of cases) All of the following criteria:
5-year PFS 82%
Any primary site
5-year survival 86%
metastases
Normal AFP
Any hCG
Any LDH
Intermediate-prognosis group
All of the following criteria:
cases)
5-year PFS 75%
Testis/retroperitoneal primary
5-year survival 80%
metastases
AFP 1,000 - 10,000 ng/mL or
hCG 5,000 - 50,000 IU/L or
LDH 1.5 - 10 x ULN
Seminoma (10% of cases) Any of the following criteria:

5-year PFS 67%
Any primary site
5-year survival 72%
Non-pulmonary visceral metastases
Normal AFP
Any hCG
Any LDH
Poor-prognosis group
Any of the following criteria:
cases)
5-year PFS 41%
Mediastinal primary
5-year survival 48%
Non-pulmonary visceral metastases
AFP > 10,000 ng/mL or
hCG > 50,000 IU/L
(10,000 ng/mL) or
LDH > 10 x ULN
Seminoma
No patients classified as poor prognosis
PFS = progression-free survival; AFP = alpha-fetoprotein;
hCG = beta-human chorionic gonadotrophin; LDH = lactate
dehydrogenase; ULN = upper limit of normal range.
uidelines for the diagnosis and staging of

G
testicular cancer
Testicular ultrasound is mandatory.
Orchidectomy and pathological examination of the
testis is necessary to confirm the diagnosis and to
define the local extension (pT category). In a lifethreatening situation due to extensive metastasis,
chemotherapy has to be started before orchidectomy.
Serum determination of tumour markers (AFP, hCG,
and LDH) must be performed before and after orchidectomy for staging and prognostic reasons.
The state of the retroperitoneal, mediastinal, and
supraclavicular nodes and visceral state must be
assessed in testicular cancer.
AFP = alpha-fetoprotein; hCG = human chorionic gonadotrophin; LDH = lactate dehydrogenase.
GR
A
A
Pathological examination of the testis

Following orchiectomy, the pathological examination of the
testis should include a number of investigations.
1. Macroscopic features: side, testis size, maximum tumour
size and macroscopic features of epididymis, spermatic
cord and tunica vaginalis.
2. Sampling: 1 cm2 section for every centimetre of maximum
tumour diameter, including normal macroscopic parenchyma (if present), albuginea and epididymis with selection of suspected areas. At least one proximal and one distal section of the spermatic cord plus any suspected area.
3. Microscopic features and diagnosis:

histological type (specify individual components
and estimate amount as a percentage);

presence or absence of peri-tumoural venous and/
or lymphatic invasion;

presence or absence of albuginea, tunica vaginalis,
rete testis, epididymis or spermatic cord invasion,
and;

presence or absence of intratubular germinal neoplasia (Tin) in non-tumoural parenchyma intratubular germ cell neoplasia.
4. pT category according to TNM 2009.
5. Immunohistochemical studies: in seminoma and mixed
germ cell tumour, AFP and hCG.

Guidelines for the treatment of testicular cancer

Seminoma stage I
Surveillance is the recommended management option
(if facilities available and patient compliant).
Carboplatin-based chemotherapy (one course at AUC
7) can be recommended.
Adjuvant treatment is not recommended for patients
at low risk.
Radiotherapy is not recommended as adjuvant treatment.
GR
A
B
A
A
NSGCT stage I
CS1 risk-adapted treatments based on vascular invasion or surveillance without using risk factors are recommended treatment options.
Risk-adapted treatments for CS1 based on vascular
invasion
CS1A (pT1, no vascular invasion): low risk
1. If the patient is willing and able to comply with
a surveillance policy, long-term (at least 5 years)
close follow-up should be recommended.
2. In low-risk patients not willing (or suitable) to
undergo surveillance, adjuvant chemotherapy or
nerve-sparing RPLND are treatment options
If RPLND reveals PN+ (nodal involvement) disease,
chemotherapy with two courses of PEB should be
considered.
CS1B (pT2-pT4): high risk
1. Primary chemotherapy with two courses of PEB
should be recommended (one course of PEB within
a clinical trial or registry).
2. Surveillance or nerve-sparing RPLND in high-risk
patients remain options for those not willing to
undergo adjuvant chemotherapy.
If pathological stage II is revealed at RPLND, further chemotherapy should be considered.
GR
Guidelines for the treatment of metastatic germ

cell tumours
GR
1. Low volume NSGCT stage IIA/B with elevated

markers should be treated like good or intermediate prognosis advanced NSGCT, with three or four
cycles of PEB.
2. In stage IIA/B without marker elevation, histology
can be gained by RPLND or biopsy. A repeat staging can be performed after six weeks of surveillance
before final decision on further treatment.
3. In metastatic NSGCT (> stage IIC) with a good
prognosis, three courses of PEB is the primary treatment of choice.
4. In metastatic NSGCT with an intermediate or poor
prognosis, the primary treatment of choice is four
courses of standard PEB and inclusion in clinical
trials is strongly recommended.
5. Surgical resection of residual masses after chemotherapy in NSGCT is indicated in the case of visible
residual masses and when serum levels of tumour
markers are normal or normalising.
6. Seminoma CS IIA/B can initially be treated with
radiotherapy. When necessary, chemotherapy can
be used as a salvage treatment with the same schedule as for the corresponding prognostic groups of
NSGCT.
B
7. In seminoma stage CS IIB, chemotherapy (4 x EP
or 3 x PEB, in good prognosis) is an alternative
to radiotherapy. It appears that 4 x EP or 3 x PEB
achieve a similar level of disease control.
A
8. Seminoma stage IIC and higher should be treated
with primary chemotherapy according to the same
principles used for NSGCT.
EP = eposide, cisplatin; NSGCT = non-seminomatous germ cell
tumour; PEB = cisplatin, eposide, bleomycin; RPLND = retroperitoneal lymph node dissection.
Relapse after chemotherapy

The treatment of relapsed GCT after chemotherapy is typically salvage chemotherapy. For patients at first relapse with
good prognostic features (initial achievement of CR/PR
M- and gonadal primary tumour) 4 cycles of standard dose
salvage chemotherapy are proposed. For patients with poor
prognostic factors (extragonadal primary and/or incomplete
response to first line chemotherapy) and for all patients with
subsequent (> first) relapse, high-dose chemotherapy with
autologous stem cell support is recommended.
Follow-up of patients with testicular cancer

The aim of the follow-up is to detect relapse as early as possible and to monitor the contralateral testis. In the presence
of a curative- or life prolongation therapy, the following principles should apply:
(a) interval between examinations and duration of follow-up
should be consistent with the time of maximal risk of
recurrence,
(b) tests should be directed at the most likely sites of recur116 Testicular Cancer
rence and have a good accuracy,

(c) the increased risk of second malignancy, both in the
primary site and in other tissues that may have been
exposed to the same carcinogens, or in which there is
epidemiological evidence of increased risk, should also
guide the ordering tests,
(d) non-malignant complications of therapy must also be
considered.
Table 5: Recommended minimum follow-up schedule in

a surveillance policy: stage I non-seminoma
Procedure
Tumour markers
Chest X-ray
Abdominopelvic
CT scan
Year 1
4 times
Year 2 Year 3-5 Year 6-10

4 times Once/yr. Once/yr.
4 times 4 times Once/yr. Once/yr.

Twice
Twice
Twice.
(at 3 and
12 mo)
CT = computed tomography.
Table 6: Recommended minimum follow-up schedule

after RPLND or adjuvant chemotherapy: stage
I non-seminoma
Procedure
Year 1
Physical exami- 4 times
nation
Tumour markers 4 times
Chest X-ray
Twice
Abdominopelvic Once
CT scan
Year 2 Year 3-5 Year 6-10

Twice
Once
Table 7: Recommended minimum follow-up schedule for

post orchidectomy surveillance, radiotherapy
or chemotherapy: stage I seminoma
Procedure
Year 1
Physical exami- 3 times
nation
Tumour markers 3 times
Chest X-ray
Twice
Abdominopelvic Twice
CT scan
Year 2 Year 3
Year 4-5
Twice
Twice
Table 8: Recommended minimum follow-up in advanced

NSGCT and seminoma
Procedure
Year 1
Year 2
Year 3-5
thereafter
Tumour markers
Chest X-ray
Abdominopelvic
CT scan*
Chest CT scan
4 times
4 times
Twice/yr.
Once/yr.
4 times
4 times
Twice/yr.
Once/yr.
4 times
Twice
4 times
Twice
As indicated
As indicated
As indicated
As indicated
Twice/yr.
As indicated
As indicated
As indicated
Once/yr.
As indicated
As indicated
As indicated
Brain CT scan
* Abdominal CT scanning must be performed at least

annually if teratoma is found in the retroperitoneum.
If the post-chemotherapy evaluation in a seminoma
patient shows any mass > 3 cm, the appropriate CT scan
should be repeated 2 and 4 months later to ensure that
the mass is continuing to regress. If available, FDG-PET
scanning can be performed.
A chest CT scan is indicated if abnormality is detected on
chest X-ray and after pulmonary resection.
In patients with headaches, focal neurological findings, or
any central nervous system symptoms.
CT = computed tomography scan; FDG-PET = fluorodeoxyglucose-positron emission tomography.
Testicular stromal tumours

Testicular stromal tumours are rare, however, Leydig cell and
Sertoli cell tumours are of clinical relevance.
Leydig cell tumours

Leydig cell tumours constitute 1-3% of adult testicular
tumours and 3% of testicular tumours in children. Only
about 10% of them are malignant presenting the following
features:
Large size (> 5 cm)
Cytologic atypia and DNA aneuploidy
Increased mitotic activity and increased MIB -1 expression
Necrosis
Vascular invasion infiltrative margins
Extension beyond the testicular parenchyma
The tumour presents as a painless enlarged testis or as an
incidental ultrasound finding accompanied in up to 80% of
cases by hormonal disorders. Serum tumour markers are
negative and approximately 30% of patients present with
gynaecomastia. These tumours are often treated by inguinal
orchiectomy because they are misinterpreted as germ cell
tumours.
Especially in patients with symptoms of gynaecomastia or
hormonal disorders or typical imaging on ultrasound, until
final histology is available, a partial orchiectomy (+ frozen
section) should be considered. In case of histological signs
of malignancy orchiectomy and RPLND are the treatment of
choice.
Sertoli cell tumours

They are even rarer than Leydig cell tumours, and they can
be malignant in 10-22% of cases. Morphological signs of
malignancy are:
Large size (> 5 cm)
Pleomorphic nuclei with nucleoli

Increased mitotic activity
Necrosis and vascular invasion
They present either as an enlarged testis or as incidental
ultrasound finding. Hormonal disorders are infrequent and
serum tumour markers are negative.
Ultrasonographically they generally appear as hypoechoic
and cannot be safely distinguished from germ-cell tumour
except for the subtype large cell calcifying form which is
usually associated with genetic syndromes (Carneys complex, Peutz-Jeghers syndrome) Sertoli cell tumours are often
interpreted as germ-cell tumours and an orchiectomy is performed.
Organ-sparing surgery should be considered (with caution) but in case of histological signs of malignancy orchiectomy and RPLND are the treatment of choice.
Conclusions
Most testis tumours derive from germ cells and are diagnosed
at an early stage. Staging is the cornerstone and the 2009
TNM system is recommended for classification and staging
purposes.
The IGCCCG staging system is recommended for metastatic
disease. Following orchiectomy, excellent cure rates are
achieved for those early stages irrespective of the treatment
policy adopted, although pattern and relapse rates are closely
linked to the treatment modality chosen. In metastatic
disease a multidisciplinary therapeutic approach offers an
acceptable survival. Follow-up schedules should be tailored
to initial staging and treatment. Testicular stromal tumours

are rare and usually benign. When suspected and pathologically confirmed they can be treated by organ sparing surgery.
However, in case of malignancy (small percentage) orchiectomy and RPLND are the treatment of choice.
GUIDELINEs ON Male Lower

Urinary Tract Symptoms (LUTS),
including Benign Prostatic
Obstruction (BPO)
M. Oelke (chairman), A. Bachmann, A. Descazeaud,

M. Emberton, S. Gravas, M.C. Michel, J. NDow, J. Nordling,
J.J. de la Rosette
The EAU Guideline on Male LUTS is a symptom-orientated
guideline that mainly reviews LUTS secondary to benign
prostatic enlargement (BPE) or benign prostatic obstruction (BPO), detrusor overactivity or overactive bladder, and
nocturia due to nocturnal polyuria in men aged 40 years or
older. The multifactorial aetiology of LUTS is illustrated in
Figure 1.
Male Lower Urinary Tract Symptoms 123
OAB detrusor
overactivity
Benign
Prostatic
Obstruction
(BPO)
And others
...
Distral
ureteral
stone
Nocturnal
polyuria
LUTS
Detrusor
underactivity
Bladder
tumour
Neurogenic
bladder
dysfunction
Urethral
stricture
Urinary
tract
infection
Prostatitis
Foreign
body
Figure 1: Causes of male lower urinary tract symptoms

(LUTS)
Assessment
Systematic diagnostic work-up is recommended (Figure 2).
History, symptom and quality-of-life questionnaire, physical
examination, urinalysis, blood analysis, ultrasound of the
prostate, bladder and kidneys, as well as uroflowmetry and
measurement of post-void residual urine are recommended
in all patients. Optional tests are bladder diary in men with
urinary frequency or nocturia; computer-urodynamic evaluation before surgical treatment should be performed in men
who:
124 Male Lower Urinary Tract Symptoms
cannot void > 150 ml;

have a maximum flow rate > 15 ml/s;
are < 50 or > 80 years of age;
can void but have post-void residual urine > 300 ml;
are suspicious of having neurogenic bladder dysfunction;
have bilateral hydronephrosis;
had radical pelvic surgery or;
had previous unsuccessful (invasive) treatment.
Note that only the diagnosis of nocturnal polyuria (> 33%

of the 24-hour urine excretion over night) can be made by
the bladder diary, whereas the diagnosis of all other forms of
non-neurogenic benign forms of LUTS in men aged 40 years
or older is mainly made by exclusion.
Figure 2: Assessment algorithm of LUTS in men aged 40

years or older
Treatment
The level of evidence and the grade of recommendation

(according to the Oxford classification system; 2001) for
with baseline values
Benign Conditions of
Bladder and/or Prostate
(in cases of nocturia or polyuria)
Bladder Diary
Uroflowmetry
(bladder, prostate, kidneys)
Ultrasound
(Na+, serum-creatinine, PSA)
Blood Analysis
(stix, sediment)
Urinanalysis
History,
Physical Examination
(e.g. IPSS)
Questionnaire with QoL
In patients with negative findings after additional evaluation
Nocturnal polyuria, polydipsia-polyuria, diabetes insipidus
Urethral stricture, dysfunctional voiding
Benign prostatic enlargement (BPE), prostate tumor/cyst,

pelvic tumour, post-void residual urine, urinary retention,
bladder stone, bladder tumour, bladder diverticulum, foreign
body in bladder, distal ureter stone, hydronephrosis
Deterioration of kidney function (e.g. due to distal ureter

stone or transitional cell carcinoma), prostatitis
Urinary tract infection, haematuria, diabetes mellitus
Neurological diseases neurogenic bladder dysfunction,

drug-induced LUTS, heart diseases with nocturnal polyuria,
penile diseases (e.g. phimosis, meatal stenosis, lichen
sclerosus, penile cancer), palbable prostate carcinoma ...
Additional tests necessary according to

abnormalities found during initial assessment
each treatment option are summarised in Table 1.
Conservative treatment
Watchful waiting (WW) is suitable for mild-to-moderate
uncomplicated LUTS. It includes education, re-assurance,
lifestyle advice, and periodic monitoring.
Drug treatment
Drugs used for the treatment of various forms of male LUTS
are listed in Table 2.
Table 2: Key pharmacokinetic properties and standard

doses of drugs licensed in Europe for the
treatment of LUTS
Drug (class)
tmax
t
Recommended
[hours]
[hours]
daily dose
1-adrenoceptor antagonists (for treating symptoms of
BPH)
Alfuzosin IR
1.5
4-6
3 x 2.5 mg
Alfuzosin SR
3
8
2 x 5 mg
Alfuzosin XL
9
11
1 x 10 mg
Doxazosin IR
2-3
20
1 x 2-8 mg
Doxazosin
8-12
20
1 x 4-8 mg
GITS
Silodosin
2.5
11-18
1 x 4-8 mg
Tamsulosin MR 6
10-13
1 x 0.4 mg
Tamsulosin
4-6
14-15
1 x 0.4 mg
OCAS
Terazosin
1-2
8-14
1 x 5-10 mg
5-reductase inhibitors (for treating benign prostatic

enlargement due to BPH)
Dutasteride
1-3
3-5 weeks 1 x 0.5 mg
Finasteride
2
6-8
1 x 5 mg
Antimuscarinic drugs (for treating OAB/storage
symptoms)
Darifenacin
7
13 - 19
1 x 7.5-15 mg
Fesoterodine
5
7
1 x 4-8 mg
Oxybutynin IR 0.5 - 1
2-4
3-4 x 2.5-5 mg
Oxybutynin ER 5
16
2-3 x 5 mg
Propiverine
2.5
13 - 20
2-3 x 15 mg
Propiverine ER 7
20
1 x 30 mg
Solifenacin
4-6
45 - 68
1 x 5-10 mg
Tolterodine IR 1 - 3
2-10
2 x 1-2 mg
Tolterodine ER 4
6 - 10
1 x 4 mg
Trospium chlo- 4 - 6
5 - 15
3 x 10-15 mg or 2
ride
x 10-20 mg
Antidiuretic (for treating nocturnal polyuria)
Desmopressin
1-2
3
1 x 0.1-0.4 mg
orally before
sleeping
Phosphodiesterase 5 Inhibitors (for treating erectile
dysfunction male LUTS [experimental])
Sildenafil
1 (0.5-2) * 3-5
1 x 25-100 mg
Tadalafil
2 (0.5-12) 17.5
1 x 2.5-20 mg
Vardenafil
1 (0.5-2) * 4-5
2 x 10 mg
ER: extended release; GITS: gastrointestinal therapeutic system; IR: immediate release; MR: modified release; OCAS: oral
controlled absorption system; SR: sustained release; tmax: time
to maximum plasma concentration; t: elimination half-life.
*dependent on food intake (i.e. slower resorption of the drug and

an increase in tmax by approximately 1 hour after a fatty meal).
1-adrenoceptor antagonists (1-blockers) are often the
first-line drug treatment of male LUTS because of their
rapid onset of action and good efficacy. They are also used
intermittently in LUTS of fluctuating symptom intensity.
The main 1-blockers are alfuzosin, doxazosin, tamsulosin
and terazosin. All 1-blockers have a similar efficacy in
mild, moderate, or severe LUTS and in different age groups.
Efficacy may be better with smaller prostates (< 40 ml). Some
patients still require surgical treatment because 1-blockers
do not reduce prostate size or prevent acute urinary retention. 1-blocker efficacy is maintained over at least 4 years.
The commonest side effects of 1-blockers are asthenia, dizziness and (orthostatic) hypotension.
5-reductase inhibitors should only be considered in men
with bothersome moderate-to-severe LUTS and enlarged
prostates (prostate volume > 40 ml) or elevated PSA concentration (> 1.4-1.6 g/l). 5-reductase inhibitors are only
suitable for long-term treatment (over many years) because
of their slow onset of action. Dutasteride and finasteride are
equally effective. Symptom reduction may not be better than
placebo in patients with prostates < 40 ml. 5-reductase
inhibitors reduce LUTS more slowly than 1-blockers and,
in finasteride, less effectively. The greater the baseline prostate volume (or serum PSA concentration), the faster and
more pronounced the symptomatic benefit of dutasteride.
5-reductase inhibitors, but not 1-blockers, reduce the
long-term (> 1 year) risk of acute urinary retention or need
for surgery. The most relevant side effects include reduced

libido, erectile dysfunction and ejaculation disorders. About
1-2% of patients develop gynaecomastia (breast enlargement
with breast or nipple tenderness).
Muscarinic receptor antagonists may benefit men with
smaller PSA levels (smaller prostates). Tolterodine significantly reduced urgency incontinence, daytime or 24-hour
frequency, and urgency-related voiding compared to placebo.
Nocturia, urgency and the International Prostate Symptom
Score (IPSS) were also reduced, though without statistical
significance. Although studies have been carried out with
tolterodine or fesoterodine, other antimuscarinic agents are
likely to show similar effects. Muscarinic receptor antagonists are generally well tolerated. Adverse effects include dry
mouth, constipation, micturition difficulties, nasopharyngitis
and dizziness. An increase in post-void residual (PVR) urine
in men without BPO is minimal. Antimuscarinic drugs are
not recommended in men with BPO because of a theoretical
decrease in bladder strength, which might be associated with
PVR or urinary retention. However, short-term treatment
with antimuscarinic drugs in men with BPO is safe. There
are no published long-term studies addressing efficacy. On
this basis, antimuscarinic drugs, especially in men with BPO,
should be prescribed with caution, and regular re-evaluations
of IPSS and PVR are advised.
Plant extracts (phytotherapy): no specific recommendations
can be made about phytotherapy in male LUTS because of
product heterogeneity, lack of regulatory framework, and
research methodological problems.
Desmopressin is a synthetic analogue of the antidiuretic hormone, arginine vasopressin, which plays a key role in body
water homoeostasis and urine production. Desmopressin is
used to treat nocturia due to nocturnal polyuria in adults.
The clinical effects (urine volume decrease, increase in urine
osmolality) last about 8-12 hours. The most frequent adverse
events are headache, nausea, diarrhoea, abdominal pain, dizziness, dry mouth, and hyponatremia (serum sodium concentration <130 mmol/l). Peripheral oedema and hypertension were reported with long-term treatment. Serum sodium
concentration should be monitored regularly to detect
hyponatremia. The risk of hyponatremia increases with age,
lower serum sodium concentration at baseline, and higher
basal 24-hour urine volume per bodyweight.
Combination therapies
1-blocker + 5-reductase inhibitor are best prescribed long
term (> 12 months) to men with moderate-to-severe LUTS
at risk of disease progression (e.g. higher prostate volume,
higher PSA concentration, advanced age). Combination treatment is better than monotherapy at reducing symptoms and
improving Qmax, and better than 1-blockers at reducing the
risk of acute urinary retention and the need for surgery. The
1-blocker may be discontinued after 6 months in men with
moderate LUTS at baseline, but longer-term combination
therapy is beneficial in severe LUTS (IPSS > 20). Adverse
events of both drug classes have been reported.
1-blocker + muscarinic receptor antagonist are more efficacious in reducing voiding frequency, nocturia, or IPSS than
1-blockers or placebo alone. Furthermore, combination
treatment significantly reduced urgency urinary incontinence

episodes and urgency and increased quality of life. Persistent
LUTS during 1-blocker treatment can be reduced by the
addition of a muscarinic receptor antagonist (tolterodine)
especially if there is detrusor overactivity. Adverse events of
both drug classes are reported. PVR measurement is recommended during combination treatment to assess increased
PVR or urinary retention.
Phosphodiesterase (PDE) 5 inhibitors are still experimental
and should not be used routinely.
Summary conservative and/or medical treatment

Behavioural with or without medical treatments are usually
the first choice of therapy. A flowchart illustrating conservative and medical treatment choices according to evidencebased medicine and patients profiles is provided in Figure 3.
Figure 3: Treatment algorithm of male lower urinary tract

symptoms (LUTS) using medical and/or conservative treatment options. Treatment decisions
depend on results assessed during initial evaluation ().The absence (-) or presence of the condition (+) are indicated in circles (o).

with or without
Watchful Waiting
Education + Lifestyle Advice
with or without
add Muscarinic
Receptor Anagonist
residual
storage
symptoms
1-blocker
with or without
prostate
volume
> 40 ml?
Male LUTS
with or without
Muscarinic Receptor
Antagonist
with or without
nocturnal
polyuria
only?
5-Reductase Inhibitor
1-blocker
long-term
treatment?
OAB storage symptoms

only?
symptom
bother,
IPSS > 7?
(without absolute indications for surgery)
Desmopressin
with or without
Surgical treatment
Prostate surgery is usually required when patients have experienced recurrent or refractory urinary retention, overflow
incontinence, recurrent urinary tract infections, bladder
stones or diverticula, treatment-resistant macroscopic hematuria due to BPH/BPE, or dilatation of the upper urinary tract
due to BPO, with or without renal insufficiency (absolute
operation indications, need for surgery). Additionally, surgery is usually needed when patients have had insufficient
relief in LUTS or PVR after conservative or medical treatments (relative operation indications).
Transurethral Resection (TURP) or Transurethral Incision
of the Prostate (TUIP): TUIP reduces BPO by splitting the
bladder outlet without tissue removal and TURP removes
tissue from the prostatic transition zone to reduce BPO
and, secondly LUTS. The choice between TURP and TUIP
is based on prostate volume with prostates < 30 ml suitable
for TUIP and prostates of 30-80 ml for TURP. Urinary tract
infections should be treated prior to surgery. Bipolar TURP
is an alternative to monopolar TURP in moderate-to-severe
LUTS secondary to BPO. It has similar efficacy but lower
morbidity.
Open prostatectomy is the oldest surgical treatment modality for moderate-to-severe LUTS secondary to BPO. Removal
of prostatic tissue resolves BPO and, secondarily, LUTS.
Efficacy is maintained > 5 years. Perioperative complications
include mortality and blood transfusion. Long-term complications are urinary incontinence and bladder neck stenosis or
urethral stricture. Open prostatectomy is the most invasive,
but also the most effective and durable procedure for treating LUTS/BPO. Only Holmium enucleation (HoLEP) delivers
similar results, but with less morbidity. In the absence of a
Holmium laser, open prostatectomy is the surgical treatment
of choice for men with prostates > 80 ml.
Transurethral Microwave Therapy (TUMT) emits microwave radiation through an intra-urethral antenna to deliver
heat into the prostate, which leads to tissue destruction,
apoptosis, and denervation of -receptors reducing BPO and
LUTS. Treatment is well tolerated, although most patients
experience perineal discomfort and urinary urgency and
require pain medication prior to or during therapy. TUMT is
an outpatient procedure and an alternative for older patients
with co-morbidities and those at risk for anaesthesia or
otherwise unsuitable for invasive treatment. Baseline parameters predicting an unfavourable outcome include small
prostates, mild-to-moderate BOO, and low energy delivered
during treatment.
Transurethral Needle Ablation (TUNA) of the prostate
delivers low-level radiofrequency energy to the prostate via
needles inserted transurethrally into the prostatic parenchyma. The energy induces coagulation necroses in the prostatic
transition zone resulting in prostate volume reduction and
resolution of BPO. TUNA is unsuitable for prostates > 75
ml or isolated bladder neck obstruction. TUNA can be performed as a day-case procedure and is associated with fewer
side effects than TURP (e.g. bleeding, erectile dysfunction,
urinary incontinence).
Holmium Laser Enucleation (HoLEP) or Holmium Laser

Resection of the Prostate (HoLRP): the holmium:yttriumaluminum-garnet (Ho:YAG) laser with a wavelength of
2140 nm is a pulsed, solid-state laser. Resection is usually
performed in prostates < 60 ml, while enucleation is used for
larger glands. Patients using anticoagulant medication and
those with urinary retention can be treated safely. Dysuria is
the most common peri-operative complication.
Laser vaporisation of prostate (KTP, Greenlight) leads
to immediate removal of prostatic tissue, relief of BPO and,
secondarily, reduction of LUTS. Because no tissue for pathological examination can be harvested, screening for prostate
cancer, if indicated, should be carried out before the laser
operation. The treatment choice of tissue ablation depends
on the availability of the armamentarium, patients choice,
concomitant morbidity or drug use, and experience of the
surgeon.
Prostate stents are an alternative to catheterisation for men
unfit for surgery. Stents require a functioning detrusor.
Insertion is usually performed in an outpatient setting under
local anaesthesia. Placement is confirmed by abdominal
ultrasonography or cystoscopy. Antibiotic prophylaxis is only
necessary with a positive urine culture.
Ethanol or botulinum toxin injections into the prostate are
still experimental.
Summary surgical treatment

The choice of the surgical technique depends primarily on
prostate size, co-morbidities of the patient, and the ability to
have anaesthesia but also on patients preferences, willingness
to accept surgery-associated side effects, availability of the
surgical armamentarium, and experience of the surgeon with
these operation techniques. A flowchart illustrating surgical
treatment choices according to patients profiles is provided
in Figure 4.
TURP
TUMT
TUNA
KTP (Greenlight)
HoLRP
HoLEP
TUIP
TURP
30 - 80
ml
prostate
volume
< 30 ml
low
> 80 ml
Open
prostatectomy
HoLEP
KTP (Greenlight)
yes
can stop
anti-coagulation?
no
KTP (Greenlight)
HoLEP
HoLRP
TUMT
TUNA
Stent
no
can have
surgery/general
anaesthesia?
yes
high
surgical risk
Male LUTS
(with indications for surgery)
Figure 4: Treatment algorithm of bothersome lower urinary

tract symptoms (LUTS) refractory to conservative/medical treatment or in cases of absolute
operation indications. The flowchart was stratified by the patients ability to have anaesthesia,
cardiovascular risk, and prostate size.
Follow-up
The below listed follow-up strategy is recommended:
patients with Watchful Waiting should be reviewed at 6
months and then annually, provided symptoms do not
deteriorate or absolute indications develop for surgical
treatment.
patients receiving 1-blockers, muscarinic receptor antagonists, or a combination of 1-blockers + 5-reductase
inhibitors or muscarinic receptor antagonists should be
reviewed 4-6 weeks after drug initiation. If patients gain
symptomatic relief in the absence of troublesome adverse
events, drug therapy may be continued. Patients should be
reviewed at 6 months and then annually, provided symptoms do not deteriorate or absolute indications develop
for surgical treatment.
patients receiving 5-reductase inhibitor monotherapy
should be reviewed after 12 weeks and 6 months to determine their response and adverse events.
in patients receiving desmopressin, serum sodium concentration should be measured at day 3 and 7 as well
as after 1 month and, if serum sodium concentration
has remained normal, every 3 months subsequently; the
follow-up sequence should be re-started after dose escalation.
patients after prostate surgery should be reviewed 4-6
weeks after catheter removal to evaluate treatment
response and adverse events. If patients have symptomatic
relief and are without adverse events further re-assessment
is not necessary.
Table 1: Level of Evidence (LE) and Grade of

Recommendation (GR) of various treatments of male
LUTS and follow-up
Conservative treatment Watchful Waiting
Men with mild symptoms are suitable for
watchful waiting.
Men with LUTS should be offered lifestyle advice prior to or concurrent with
treatment.
Drug treatment
1.
1-blockers should be offered to men
with moderate-to-severe LUTS.
2.
5-reductase inhibitors should be offered
to men who have moderate-to-severe
LUTS and an enlarged prostate (> 40
ml). 5-reductase inhibitors can prevent
disease progression with regard to acute
urinary retention and need for surgery.
3.
Muscarinic receptor antagonists might
be considered in men with moderate-tosevere LUTS who have predominantly
bladder storage symptoms.
Caution is advised in men with bladder
outlet obstruction (BOO).
4.
Desmopressin can be used for the treatment of nocturia due to nocturnal polyuria.
LE
GR
1b
1b
1a
1b
1b
1b
5.
6.
7.
Combination treatment with an

1-blocker together with a 5-reductase
inhibitor should be offered to men with
bothersome moderate-to-severe LUTS,
enlarged prostates, and reduced Qmax
(men likely to develop disease progression).
Combination treatment is not recommended for short-term therapy (< 1
year).
Combination treatment with an
1-blocker together with a muscarinic
receptor antagonists might be considered
in patients with bothersome moderateto-severe LUTS if symptom relief has
been insufficient with the monotherapy
of either drug. Combination treatment
should cautiously be prescribed in men
with suspected BOO.
PDE5 inhibitors reduce moderate-tosevere male LUTS but are experimental
and restricted to men with erectile dysfunction, pulmonary arterial hypertension, or to those who have bothersome
LUTS in clinical trials.
1b
1b
2b
1b
Surgical treatment
1.
Monopolar TURP is the current surgical
standard procedure for men with prostate sizes of 30-80 ml and bothersome
moderate-to-severe LUTS secondary of
BPO. Monopolar TURP provides subjective and objective improvement rates
superior to medical or minimally invasive
treatments.
Bipolar TURP achieves short-term results
comparable to monopolar TURP.
TUIP is the surgical therapy of choice for
men with prostate sizes < 30 ml, without
a middle lobe, and bothersome moderateto-severe LUTS secondary to BPO.
2.
Open prostatectomy is the first choice of
surgical treatment in men with prostate
sizes > 80 ml, bothersome moderateto-severe LUTS secondary to BPO, and
LUTS refractory to drugs in the absence
of a Holmium laser.
Open prostatectomy is the most invasive
surgical method with significant morbidity.
3.
TUMT achieves symptom improvement
comparable to TURP, but is associated
with decreased morbidity and lower flow
improvements.
Durability is in favour of TURP with
lower re-treatment rates compared to
TUMT.
1a
1a
1a
1b
1b
1a
1a
4.
5.
6.
7.
TUNA is an alternative to TURP for

patients who wish to defer/avoid (complications of) TURP, but patients should
be aware of significant re-treatment rates
and less improvement in symptoms and
quality of life.
HoLEP and 532 nm laser vaporisation
of the prostate are minimally invasive
alternatives to TURP in men with moderate-to-severe LUTS due to BPO. Laser
operations lead to immediate, objective
and subjective improvements comparable
to TURP.
With regard to intra-operative safety,
532 nm laser vaporisation is superior
to TURP and should be considered in
patients receiving anticoagulant medication or with high cardiovascular risk.
With regard to long-term complication rates, results are only available for
HoLEP and are comparable to TURP.
Prostatic stents are an alternative to
catheterisation for men unfit for surgery.
Stents may have a role in the temporary
relief of LUTS/BPO after minimally invasive treatment.
Intra-prostatic ethanol injections for men
with moderate-to-severe LUTS secondary
to BPO are still experimental and should
be performed only in clinical trials.
1a
1b
1b
8.
Intra-prostatic BTX injections for men

3
with bothersome moderate-to-severe
LUTS secondary to BPO or men in urinary retention are still experimental and
should be performed only in clinical
trials.
Follow-up
3-4
Follow-up for all conservative, medical or operative treatment modalities is
based on empirical data or theoretical
considerations but not on evidence based
studies.
GUIDELINES ON MALE SEXUAL

DYSFUNCTION: Erectile Dysfunction
and Premature Ejaculation
(Text update March 2009)
E. Wespes, E. Amar, I. Eardley, F. Giuliano, D. Hatzichristou,

K. Hatzimouratidis, F. Montorsi, Y. Vardi
Eur Urol 2002;41(1):1-5
Eur Urol 2006;49(5):806-15
ERECTILE DYSFUNCTION
Definition, epidemiology and risk factors
Erectile dysfunction (ED) is the persistent inability to attain
and maintain an erection sufficient to permit satisfactory sexual performance. Although ED is a benign disorder, it affects
physical and psychosocial health and has a significant impact
on the quality of life (QoL) of sufferers and their partners
and families. Approximately 5-20% of men have moderate to
severe ED.
Erectile dysfunction shares common risk factors with cardiovascular disease including lack of exercise, obesity, smoking,
hypercholesterolaemia, and the metabolic syndrome. The
risk of ED may be reduced by modifying these risk factors,
particularly taking exercise or losing weight. Another risk
factor for ED is radical prostatectomy (RP) in any form
(open, laparoscopic, or robotic) because of the risk of cavernosal nerve injury, poor oxygenation of the corpora cavernosa,
Male Sexual Dysfunction 145
and vascular insufficiency. About 25-75% of men undergoing

RP experience post-operative ED. Patients being considered
for nerve-sparing radical prostatectomy (NSRP) should ideally be potent and the cavernosal nerves must be preserved to
ensure erectile function recovery after RP.
Diagnosis and work-up

Basic work-up
The basic work-up (minimal diagnostic evaluation) outlined
in Figure 1 must be performed in every patient with ED.
Due to the potential cardiac risks associated with sexual
activity, the 2nd Princeton Consensus Conference stratified
patients with ED wanting to initiate, or resume, sexual activity into three risk categories. The low-risk group includes
asymptomatic patients with less than three risk factors for
coronary artery disease (excluding male gender), mild or
stable angina (evaluated and/or being treated), uncomplicated past myocardial infarction, left ventricular dysfunction
or congestive heart failure (NYHA class I), post-successful
coronary revascularisation, controlled hypertension, and
mild valvular disease. All other patients are included in an
intermediate- or high-risk category and require a cardiology
consultation.
Specific examinations and tests
Although most patients with ED can be managed within the
sexual care setting, some circumstances require specific diagnostic testing:
Patients with primary erectile disorder (not caused by
organic disease or psychogenic disorder).
146 Male Sexual Dysfunction
Y
oung patients with a history of pelvic or perineal
trauma who could benefit from potentially curative vascular surgery.
Patients with penile deformities (e.g. Peyronies
disease, congenital curvature) that might require surgical
correction.
Patients with complex psychiatric or psychosexual
disorders.
Patients with complex endocrine disorders.
Specific tests may also be indicated at the request of the
patient or his partner.
For medico-legal reasons (e.g. penile prosthesis implant,
sexual abuse).
Specific diagnostic tests include:
nocturnal penile tumescence and rigidity (NTPR) using
Rigiscan;
vascular studies:
- intracavernous vasoactive drug injection;
- duplex ultrasound of the cavernous arteries;
- dynamic infusion cavernosometry/cavernosography
(DICC);
- internal pudendal arteriography;
neurological studies (e.g. bulbocavernosus reflex latency,
nerve conduction studies);
endocrinological studies;
specialised psychodiagnostic evaluation.
The NPTR should take place for at least two nights. A functional erectile mechanism is indicated by an erectile event of
at least 60% rigidity recorded on the tip of the penis, lasting
for 10 min or longer.
The intracavernous injection test provides limited information about vascular status. However, Duplex ultrasound
provides a simple way of assessing vascular status. Further
vascular investigation is unnecessary if Duplex ultrasound is
normal, as indicated by a peak systolic blood flow > 30 cm/s
and a resistance index > 0.8. If ultrasound is abnormal, however, arteriography and DICC should be performed only in
patients who are potential candidates for vascular reconstructive surgery.
Recommendations for the diagnostic work-up LE GR

Clinical use of a validated questionnaire related
to ED may help assess all sexual function
domains and the effect of a specific treatment
modality.
Physical examination is needed in the initial
assessment of ED to identify underlying medical
conditions associated with ED.
Routine laboratory tests, including glucose-lipid
profile and total testosterone, are required to
identify and treat any reversible risk factors and
modifiable lifestyle factors.
Specific diagnostic tests are indicated by only a
few conditions.
ED = erectile dysfunction.
Figure 1: Minimal diagnostic evaluation (basic work-up) in

patients with erectile dysfunction
Patient with erectile dysfunction (self-reported)
Medical and psychosexual history

(use of validated instruments, e.g. IIEF)
Identify
sexual
problems
other than
ED
Identify
common
causes of
ED
Identify
reversible
risk factors
for ED
Assess psychosocial
status
Focused physical examination
Penile
deformities
Prostatic
disease
Signs of
hypogonadism
Cardiovascular and
neurological status
Laboratory tests
Glucose-lipid profile
(if not assessed in the
last 12 months)
Total testosterone
(morning sample)
If available: bio-available
or free testosterone
(instead of total)
IIEF = International Index for Erectile Function.

Treatment of ED
Only certain types of ED have the potential to be cured with
specific treatments:
Psychogenic ED: psychosexual therapy may be given
either alone or with another therapeutic approach, but
takes time and has had variable results.
Post-traumatic arteriogenic ED in young patients: surgical
penile revascularisation has a 60-70% long-term success
rate.
Hormonal causes of ED: testosterone replacement therapy
is effective, but should only be used after other endocrinological causes for testicular failure have been excluded.
Currently, it is contraindicated in men with a history of
prostate carcinoma or with symptoms of prostatism. Close
follow-up is necessary, including digital rectal examination (DRE), serum prostate-specific antigen (PSA) and
haematocrit assessment, as well as monitoring the development of hepatic or prostatic disease.
The use of pro-erectile drugs following RP is very important
in achieving erectile function after surgery. Several trials have
shown higher rates of recovery of post-RP erectile function
in patients receiving any phosphodiesterase type 5 (PDE5)
inhibitor or intracavernosal injections (therapeutic or prophylactic). Rehabilitation should start as soon as possible following RP.
Most men with ED will be treated with treatment options
that are not cause-specific. This approach requires a structured treatment strategy that depends on efficacy, safety,
invasiveness, and cost, as well as patient and partner satisfac150 Male Sexual Dysfunction
tion. A treatment algorithm for ED is given in Figure 2.
First-line therapy
Oral pharmacotherapy
Three potent, selective PDE5 inhibitors have been approved
by the European Medicines Agency (EMA) for the treatment
of ED. They are not initiators of erection and require sexual
stimulation for an erection to occur. Efficacy is defined as
rigidity sufficient for vaginal penetration.
Sildenafil (Viagra)
Sildenafil was the first PDE5 inhibitor available. It is effective after 30-60 min from administration. A heavy, fatty meal
may reduce or prolong absorption. It is administered in 25,
50 and 100 mg doses. The recommended starting dose is
50 mg and adapted according to patient response and sideeffects. Efficacy may last for up to 12 h. Efficacy may last for
up to 12 h. Efficacy rates (erections sufficient for successful
intercourse) are 56%, 77% and 84% of men taking 25, 50 and
100 mg of sildenafil, respectively. The efficacy of sildenafil
in almost every subgroup of patients with ED has been well
established.
Tadalafil (Cialis)
Tadalafil is effective from 30 min after administration but its
peak efficacy occurs after about 2 h. Efficacy is maintained
for up to 36 h and is not affected by food. It is administered
in 10 and 20 mg doses. The recommended starting dose is
10 mg and is adapted according to patient response and sideeffects. Efficacy rates are 67% and 81% of men taking 10 mg
and 20 mg of tadalafil, respectively. Tadalafil also improves
erections in difficult-to-treat subgroups.

Vardenafil (Levitra)
Vardenafil is effective after 30 min from administration. A
fatty meal > 57% in fat reduces its effect. It is administered in
5, 10 and 20 mg doses. The recommended starting dose is 10
mg and adapted according to the response and side-effects. In
vitro, it is 10-fold more potent than sildenafil. However, this
does not necessarily mean greater clinical efficacy. Efficacy
rates are 66%, 76% and 80% of men taking 5 mg, 10 mg and
20 mg of vardenafil, respectively. Vardenafil also improves
erections in difficult-to-treat subgroups.
Choice of, or preference for, different PDE5 inhibitors
The choice of a PDE5 inhibitor depends on the frequency
of intercourse (occasional use or regular therapy, 3-4 times
weekly) and the patients personal experience of the agent.
Patients need to know whether a drug is short- or long-acting, possible disadvantages, and how to use it.
On-demand or chronic use of PDE5 inhibitors
Although PDE5 inhibitors were introduced as on-demand
treatment, in 2008, tadalafil was also approved for continuous, everyday use in 2.5 and 5 mg doses. Daily dosing was
well tolerated and significantly improved erectile function.
Similar results have been found in diabetic patients. Daily
tadalafil provides an alternative to on-demand dosing for
couples that prefer spontaneous rather than scheduled sexual
activity or who have frequent sexual activity.
Adverse events
Common adverse events include headache, flushing, dizziness, dyspepsia, and nasal congestion. Sildenafil and vardenafil have been associated with visual abnormalities in less than
2% of patients, while tadalafil has been associated with back
pain/myalgia in 6% of patients. However, adverse events are
generally mild in nature, self-limited by continuous use, and
the dropout rate due to adverse events is similar to placebo.
Cardiovascular safety
Clinical trials and post-marketing data of all PDE5 inhibitors
have demonstrated no increase in myocardial infarction rates.
No PDE5 inhibitor has adversely affected total exercise time
or time to ischaemia during exercise testing in men with stable angina. In fact, they may improve exercise tests.
Nitrates are totally contraindicated with all PDE5 inhibitors
due to unpredictable hypotension. The duration of interaction between organic nitrates and PDE5 inhibitors varies
according to the PDE5 inhibitor and nitrate. If a patient
develops angina while using a PDE5 inhibitor, other antiangina agents may be used instead of nitroglycerine or until
after the appropriate time has passed (24 h for sildenafil or
vardenafil and 48 h for tadalafil).
In general, the adverse event profile of the PDE5 inhibitor is
not worsened, even when the patient is on multiple antihypertensive agents.
Alpha-blocker interactions
All PDE5 inhibitors appear to interact with alpha-blockers,
which under some conditions may result in orthostatic

hypotension. The labelling for sildenafil currently includes
a precaution advising that 50 or 100 mg (not 25 mg) of
sildenafil should not be taken within 4 h of taking an alphablocker. The use of vardenafil with an alpha-blocker is not
recommended. However, co-administration of vardenafil with
tamsulosin is not associated with clinically significant hypotension. Tadalafil is contraindicated in patients taking alphablockers, except for tamsulosin.
Dosage adjustments
Lower doses of PDE5 inhibitors may be required in patients
taking ketoconazole, itraconazole, erythromycin, clarithromycin, and HIV protease inhibitors (ritonavir, saquinavir). Higher doses of PDE5 inhibitors may be necessary in
patients taking rifampicin, phenobarbital, phenytoin, or
carbamazepine. Kidney or hepatic dysfunction may require
dose adjustments. In patients with hypogonadism, androgen
supplementation improves erectile response.
Management of non-responders to PDE5 inhibitors
Physicians should check that the patient is using a licensed
medication and that the medication has been properly prescribed and correctly used (adequate sexual stimulation,
dosage, and enough time between taking the medication and
attempt at intercourse).
Provided a patient is using a PDE5 inhibitor appropriately,
there are several ways of improving efficacy. They include
modification of associated risk factors, treatment of associated hypogonadism, changing to another PDE5 inhibitor, or
continuous use of a PDE5 inhibitor.

Vacuum constriction devices
A vacuum constriction device (VCD) applies a negative pressure to the penis to draw venous blood into the penis, which
is then retained by application of a visible constricting band
at the base of the penis. This method is more acceptable to
older patients. Efficacy, defined by an erection satisfactory
for intercourse, is as high as 90%. Satisfaction rates range
between 27% and 94%. Adverse events include penile pain,
numbness, and delayed ejaculation and occur in less than
30% of patients.
Second-line therapy
Patients not responding to oral drugs may be offered intracavernous injections. Alprostadil (Caverject, Edex/Viridal)
is the only drug approved for intracavernous treatment of
ED. It is the most efficacious monotherapy for intracavernous treatment using 5-40 g doses. The patient should be
enrolled in an office-based training programme (one or two
visits) to learn the correct injection process.
Efficacy rates are about 70% with reported sexual activity
after 94% of injections and satisfaction rates of 87-93.5% in
patients and 86-90.3% in partners. Dropout rates of 41-68%
have been described, with most dropouts occurring within
the first 2-3 months. Complications of intracavernous
alprostadil include penile pain (50% of patients), prolonged
erections (5%), priapism (1%), and fibrosis (2%). Drug combinations (mainly the three-drug combination of alprostadil
+ papaverine + phentolamine) may increase efficacy by up
to 90%. Fibrosis was found to be more common (5-10%) if

papaverine was used (depending on total dose).
After 4 h of erection, patients are advised to consult their
doctor to avoid any damage to the intracavernous muscle, as
this will result in permanent impotence. Blood aspiration and
injection of phenylephrine are used to treat prolonged erections. If this problem occurs, the dosage of the next intracavernosal injection is usually reduced.
Prostaglandin E1 may be administered intraurethrally as a
semi-solid pellet (125-1000 g). A band placed at the base of
the penis improves the resulting rigidity. The clinical success
rate is lower than with intracavernosal injections, but about
70% of patients are satisfied or very satisfied with treatment.
Side-effects include local pain (29-41%), dizziness (1.9-14%),
and urethral bleeding (5%).
Third-line therapy (penile prostheses)

Surgical implantation of a penile prosthesis may be considered in patients who fail pharmacotherapy or who want a
permanent solution. Prostheses are either malleable (semirigid) or inflatable (two- or three-piece). Most patients prefer the three-piece inflatable devices because erections are
more natural, but these implants are much more expensive.
Satisfaction rates of 70-87% are reported from patients after
appropriate consultation.
Complications include mechanical failure (less than 5%
after 5-year follow-up with currently available three-piece
prostheses) and infection. With antibiotic prophylaxis, the
infection rate is 2-3% and may be further reduced by using

an antibiotic-impregnated or hydrophilic-coated implant.
Infection requires removing the prosthesis, antibiotic administration and re-implantation after 6-12 months. However,
82% success rates have been achieved using salvage therapy,
involving removal and re-implantation immediately following copious irrigation of the corpora with a multi-antibiotic
solution.
Recommendations for ED Treatment

Lifestyle changes and risk factor modification
must precede or accompany ED treatment.
Pro-erectile treatments have to be given at the
earliest opportunity after radical prostatectomy.
If a curable cause of ED is found, treat the cause
first.
PDE5 inhibitors are first-line therapy.
Daily administration of PDE5 inhibitors may
improve results and restore erectile function.
Inadequate/incorrect prescription and poor
patient education are the main causes of a lack of
response to PDE5 inhibitors.
Testosterone replacement restores efficacy in
hypogonadic non-responders to PDE5 inhibitors.
Apomorphine can be used in mild-to-moderate
ED, psychogenic ED, or in patients with contraindications to PDE5 inhibitors.
A vacuum constriction device can be used in
patients with stable relationship.
Intracavernous injection is second-line therapy.
Penile implant is third-line therapy.
LE
1b
GR
A
1b
1b
1a
1b
A
A
1b
1b
1b
4
B
C
PDE5 inhibitor = phosphodiesterase type 5 inhibitor.

Figure 2: Treatment algorithm for ED

Treatment of erectile dysfunction
Identify and treat
curable causes
of ED
Lifestyle changes
and risk factor
modification
Provide education
and counselling to
patients and partners
Identify patient needs and expectations

Shared decision-making
Offer conjoint psychosocial and medical treatment
PDE5
inhibitors
Apomorphine SL
Intracavernous injections
Intraurethral alprostadil
Vacuum devices
Assess therapeutic outcome:

Erectile response
Side-effects
Satisfaction with treatment
Inadequate treatment outcome
Assess adequate use of treatment options
Provide new instructions and counselling
Re-trial
Consider alternative or combination therapy
Inadequate treatment outcome
Consider penile prosthesis implantation
PDE5 inhibitor = phosphodiesterase type 5 inhibitor.

PREMATURE EJACULATION
Definition, epidemiology and risk factors
While defining premature ejaculation (PE) proves to be difficult, the International Society for Sexual Medicine (ISSM)
has adopted a completely new definition of lifelong PE,
which is the first evidence-based definition: Premature ejaculation is a male sexual dysfunction characterized by ejaculation
which always or nearly always occurs prior to or within about
one minute of vaginal penetration; and inability to delay ejaculation on all or nearly all vaginal penetrations; and negative
personal consequences, such as distress, bother, frustration and/
or the avoidance of sexual intimacy.
Thus, PE may be classified as lifelong (primary) or acquired
(secondary). Lifelong PE is characterised by onset from the
first sexual experience and remains a problem during life.
Acquired PE is characterised by a gradual or sudden onset
with ejaculation being normal before onset of the problem.
Time to ejaculation is short, but not usually as fast as in lifelong PE.
The prevalence of acquired PE is 20-30%; the prevalence of
lifelong PE is 2-5%. The aetiology of PE is unknown, with
little data to support suggested biological and psychological
hypotheses, including anxiety, penile hypersensitivity, and
serotonin receptor dysfunction. In contrast to ED, the prevalence of PE is not affected by age. Risk factors for PE are
generally unknown.
Premature ejaculation has a detrimental effect on self-confidence and relationship with the partner. It may cause mental
distress, anxiety, embarrassment, and depression. However,

most men with PE do not seek help.
Diagnostic work-up
Diagnosis of PE is based on the patients medical and sexual
history. The history should classify PE as lifelong or acquired
and determine whether PE is situational (under specific circumstances or with a specific partner) or consistent. Special
attention should be given to the length of time of ejaculation,
degree of sexual stimulus, impact on sexual activity and QoL,
and drug use or abuse. It is also important to distinguish PE
from ED.
Recommendations for diagnosis of PE

Diagnosis and classification of PE is based on
medical and sexual history.
It should be multidimensional and assess IELT,
perceived control, distress, and interpersonal difficulty due to the ejaculatory dysfunction.
Clinical use of self-estimated IELT is adequate.
Stopwatch-measured IELT is necessary in clinical trials.
Patient-reported outcomes have the potential to
identify men with PE. Further research is needed
before they can be recommended for clinical use.
Physical examination may be necessary in initial
assessment of PE to identify underlying medical
conditions associated with PE or other sexual
dysfunctions particularly ED.
LE
GR
1a
2a
outine laboratory or neurophysiological tests

R
are not recommended. Additional tests should
be directed by specific findings from history or
physical examination.
IELT = intravaginal ejaculatory latency time.
Treatment of PE
In many relationships, PE causes few if any problems. In
such cases, treatment should be limited to psychosexual
counselling. Before beginning treatment, it is essential to
discuss patient expectations thoroughly. Erectile dysfunction
or other sexual dysfunction or genitourinary infection (e.g.
prostatitis) should be treated first or at the same time as PE.
Various behavioural techniques have demonstrated benefit
in treating PE. In lifelong PE, behavioural techniques are not
recommended for first-line treatment. They are time-intensive, require the support of a partner, and can be difficult
to do. Pharmacotherapy is the basis of treatment in lifelong
PE but all medical treatments are off-label indications. Only
chronic selective serotonin reuptake inhibitors (SSRIs) and
on-demand topical anaesthetic agents have consistently
shown efficacy in PE. A treatment algorithm for PE is presented in Figure 3.
Psychological/behavioural strategies
Behavioural strategies mainly include the stop-start programme developed by Semans and its modification, the
squeeze technique, proposed by Masters and Johnson (several modifications exist). Masturbation before anticipation
of sexual intercourse is another technique used by many
younger men.
Overall, success rates of 50-60% have been reported short
term. Improvements achieved with these techniques are generally not maintained long term.
Topical anaesthetic agents
Lidocaine-prilocaine cream (5%) is applied for 20-30 min
prior to intercourse. A condom is required to avoid diffusion
of the topical anaesthetic agent into the vaginal wall causing
numbness in the partner. In two RCTs, lidocaine-prilocaine
cream significantly increased the stopwatch-measured IELT
compared to placebo. No significant side-effects have been
reported. An aerosol formulation of lidocaine 7.5 mg plus
prilocaine 2.5 mg (Topical Eutectic Mixture for Premature
Ejaculation, TEMPE) is under evaluation and has shown
similar results.
SS-cream is a topical anaesthetic agent made from the
extracts of nine herbs. It is applied to the glans penis 1 h
before and washed off immediately prior to coitus. In a RCT,
application of 0.2 g SS-cream significantly improved IELT
and satisfaction compared to the placebo group. Mild local
burning and mild pain were reported by 18.5% of patients.
No adverse effects on sexual function or partner or systemic
side-effects were observed.
Selective serotonin reuptake inhibitors
Commonly used selective serotonin reuptake inhibitors
(SSRIs) include paroxetine (20-40 mg/day), sertraline (25200 mg/day), and fluoxetine (10-60 mg).
Selective serotonin reuptake inhibitors were expected to

increase the geometric mean IELT by 2.6-fold to 13.2-fold.
Paroxetine was found to be superior to fluoxetine, clomipramine, and sertraline. Ejaculation delay may start a
few days after drug intake, but it is more evident after 1-2
weeks and may be maintained for several years. Common
side-effects of SSRIs include fatigue, drowsiness, yawning,
nausea, vomiting, dry mouth, diarrhoea, and perspiration;
they are usually mild and gradually improve after 2-3 weeks.
Decreased libido, anorgasmia, anejaculation, and ED have
been also reported. On-demand treatment is inferior to daily
dosing, but may be combined with an initial trial of daily
treatment or concomitant low-dose daily treatment to reduce
adverse effects.
Dapoxetine is a potent SSRI, which has been specially
designed as an on-demand oral treatment for PE. An integrated analysis of two RCTs reported that dapoxetine, 30 and
60 mg, improved IELT significantly compared to placebo.
Improved ejaculation control was reported by 51% and 58%
of patients in the 30 mg and 60 mg dosage groups, respectively. Both dapoxetine doses were effective on the first dose.
Common adverse events were nausea, diarrhoea, headache,
and dizziness. Dapoxetine has been approved (December
2008) for the on-demand treatment of PE in seven European
countries (Sweden, Austria, Finland, Germany, Spain, Italy,
and Portugal). This is currently the first and only drug
approved for such an indication.
Phosphodiesterase type 5 inhibitors
Several recent studies have supported the therapeutic role
of PDE5 inhibitors in PE. However, there is only one RCT

comparing sildenafil to placebo. Although IELT was not significantly improved, sildenafil increased confidence, the perception of ejaculatory control and overall sexual satisfaction,
reduced anxiety, and decreased the refractory time to achieve
a second erection after ejaculation.
Recommendations for PE treatment

Erectile dysfunction, other sexual dysfunction, or genitourinary infection (e.g. prostatitis)
should be treated first.
Behavioural techniques can benefit PE. However,
they are time intensive, require the support of a
partner, and can be difficult to do.
Pharmacotherapy is the basis of treatment in
lifelong PE.
Daily SSRIs are first-line, off-label, pharmacological treatment for PE. The pharmacokinetic profile of currently available SSRIs is not amenable
to on-demand dosing.
Dapoxetine, a short-acting SSRI, has already
been approved for the on-demand treatment of
PE in seven European countries.
Topical anaesthetic agents provide viable alternatives to SSRIs (off-label).
A trial of PDE5 inhibitors may be attempted.
Recurrence is likely after treatment cessation.
Behavioural therapy may augment pharmacotherapy to enhance prevention of relapse.
SSRI = selective serotonin reuptake inhibitor.
LE
2a
GR
B
1a
1a
1a
1b
2B
1b
3
C
A
C
Figure 3: Management of PE
Clinical diagnosis of premature ejaculation
based on patient/partner history
Time to ejaculation (IELT)
Perceived degree of ejaculatory control
Degree of bother/distress
Onset and duration of PE
Psychosocial/Relationship issues
Medical history
Treatment of premature ejaculation

Patient counselling
Discussion of treatment options
If PE is secondary to ED, treat ED first or concomitantly
Lifelong PE
Pharmacotherapy
Relationship counselling
Behavioural therapy
Combination treatment
Lifelong PE
Behavioural therapy
Pharmacotherapy
Relationship counselling
Combination treatment
Attempt graduated withdrawal of Drug therapy after 6-8 weeks

Behavioural therapy includes stop/start technique, squeeze and sensate
focus
Pharmacotherapy (off label) includes SSRIs (daily use) and topical anaesthetics; it is recommended as first-line treatment option in lifelong PE
Consider dapoxetine for on-demand use (the only approved drug for PE)
PE = premature ejaculation; IELT = intravaginal ejaculatory

latency time; ED = erectile dysfunction; SSRI = selective serotonin receptor inhibitor.
Adapted from Lue et al. Summary of the recommendations on
sexual dysfunctions in men. J Sex Med 2004;1:6-23.
GUIDELINES ON
penile curvature
E. Wespes (chairman), K. Hatzimouratidis (vice-chair),
I. Eardley, F. Giuliano, D. Hatzichristou, I. Moncada,
A. Salonia, Y. Vardi
Congenital penile curvature

Congenital penile curvature has an unknown cause and a
prevalence rate of 4-10% in the absence of urethral abnormalities. It is diagnosed from the medical and sexual history.
Physical examination during erection helps to document
curvature and exclude other pathologies. Erectile function is
normal, but can be compromised by excessive curvature.
Congenital penile curvature can only be treated surgically,
using the same principles as in Peyronies disease (see below),
except surgery can be performed at any time in adults.
Surgery is almost exclusively plication, resulting in high curvature correction rates of 67-97%.
Peyronies disease
Epidemiology, physiopathology and natural history
The cause of Peyronies disease is unknown, but the most
widely accepted hypothesis is trauma to the tunica albuginea. The most commonly associated comorbidities and
risk factors are diabetes, hypertension, lipid abnormalities,
ischaemic cardiopathy, erectile dysfunction, smoking and
excessive alcohol consumption. It has a prevalence rate
of 0.4-9%. Dupuytrens contracture is more common in
Penile Curvature 167
Peyronies disease (9-39%), while Peyronies disease occurs in

4% of patients with Dupuytrens contracture. However, it is
unclear if these factors contribute to the pathophysiology of
Peyronies disease.
Two phases of the disease can be distinguished. The first is
the acute inflammatory phase, which may be associated with
pain. The second is the fibrotic phase, identified by formation of hard palpable plaques that can be calcified, which
results in disease stabilisation. With time, penile curvature
is expected to worsen in 30-50% of patients or stabilise in
47-67% of patients. Spontaneous improvement has been
reported by only 3-13% of patients and is more likely early in
the disease. Pain tends to resolve with time in 90% of men,
usually during the first 12 months after disease onset.
Patient evaluation
Particular attention should be given to whether the disease
is still active, as this will influence medical treatment or the
timing of surgery. Patients most likely to have active disease
are those with short symptom duration, pain during erection, or a recent change in penile curvature. Resolution of
pain and stability of the curvature for at least 3 months are
well-accepted criteria for disease stabilisation and referral for
surgical intervention.
A palpable node or plaque is usually identified on a routine
genitourinary assessment. However, there is no correlation
between plaque size and degree of curvature. The measurement of length during erection is important because
it impacts directly on treatment decisions. An objective
168 Penile Curvature
assessment of penile curvature with an erection is mandatory. This can be obtained by a home (self) photograph of a
(preferably) natural erection, a vacuum-assisted erection, or
an intracavernosal injection using vasoactive agents. Erectile
dysfunction is common (> 50%) due to penile vascular disease. The presence of erectile dysfunction may impact on
treatment strategy.
Sonographic measurement of the plaques size is inaccurate
and operator-dependent and is not recommended in everyday clinical practice. Duplex ultrasonography may be necessary to assess vascular parameters.
Non-operative treatment
Conservative treatment of Peyronies disease is primarily
focused on patients in the early stages of disease. Several
options have been suggested, including oral pharmacotherapy (vitamin E, potassium para-aminobenzoate, tamoxifen,
colchicine, acetyl esters of carnitine, pentoxifylline), intralesional injection therapy (steroids, verapamil, clostridial collagenase, interferon) and other topical treatments (verapamil,
iontophoresis, extracorporeal shock wave therapy, traction
devices, vacuum devices).
The role of conservative treatment in men with stable/
chronic disease has not yet been adequately defined. No
single drug has been approved by the European Medical
Association for the treatment of Peyronies disease.
The results of the studies on conservative treatment for
Peyronies disease are often contradictory because of several
methodological problems that make it difficult to provide

recommendations in everyday real life.
Recommendations on non-operative treatment for Peyronies disease
LE
GR
Conservative treatment for Peyronies disease is

primarily aimed at treating patients in the early
stages of disease. It is an option in patients not
fit for surgery or when surgery is not acceptable to the patient.
Oral treatment with potassium para-aminobenzoate may result in a significant reduction
in penile plaque size and penile pain and an
increase in penile curvature stabilisation.
Intralesional treatment with verapamil may
result in a significant reduction in penile curvature and plaque volume.
Intralesional treatment with clostridial collagenase showed significant decreases in the
deviation angle, plaque width and plaque
length.
Intralesional treatment with interferon may
improve penile curvature, plaque size and density, and pain.
Topical verapamil gel 15% may improve penile
curvature and plaque size.
Iontophoresis with verapamil 5 mg and dexamethasone 8 mg may improve penile curvature
and plaque size.
1b
1b
2b
1b
1b
1b
Extracorporeal shock-wave treatment fails

to improve penile curvature and plaque size,
and should not be used to reduce plaque size.
However, it may help improve penile pain.
Penile traction devices and vacuum devices
may reduce penile deformity and increase
penile length.
Recommendations AGAINST
Intralesional treatment with steroids do not
reduce penile curvature, plaque size or penile
pain and are not recommended.
Oral treatment with vitamin E and tamoxifen is
not recommended.
Other oral treatments (acetyl esters of carnitine, pentoxifylline) are not recommended.
1b
1b
2b
Surgical treatment
Although conservative treatment for Peyronies disease
should resolve painful erections in most men, only a small
percentage experience any significant straightening of the
penis. The aim of surgery is to correct curvature and allow
satisfactory intercourse. Surgery is indicated only in patients
with stable disease for at least 3 months, although a 6-12
month period has also been suggested.
Two major types of repair may be considered for both congenital penile curvature and Peyronies disease: penile shortening and penile lengthening procedures. Penile shortening
procedures include the Nesbit wedge resection and the plication techniques performed on the convex side of the penis.
Penile lengthening procedures are performed on the concave
side of the penis and require the use of a graft. They are used
to minimise penile shortening caused by Nesbit resection

or plication of the tunica albuginea or to correct complex
deformities. Several types of grafts include autologous grafts
(dermis, vein grafts, tunica albuginea, tunica vaginalis, temporalis fascia, buccal mucosa), allografts (cadaveric pericardium, cadaveric fascia lata, cadaveric dura matter, cadaveric
dermis), xenografts (porcine small intestine submucosa,
bovine pericardium, porcine dermis) and synthetic grafts
(Gore-Tex, Dacron). Finally, in patients with Peyronies disease and erectile dysfunction not responding to medical treatments, surgical correction of the curvature with concomitant
penile prosthesis implantation should be considered.
The decision on the most appropriate surgical procedure to
correct penile curvature is based on pre-operative assessment of penile length, the degree of the curvature, and
erectile function status. The results of the different surgical
approaches are presented in Table 1. It must be emphasised
that there are no randomised controlled trials available
addressing surgery in Peyronies disease. The treatment algorithm is presented in Figure 1.
Guidelines recommendations on surgical

treatment for penile curvature
LE
Surgery is indicated when Peyronies disease

3
is stable for at least 3 months (without pain or
deformity deterioration), which usually occurs
after 12 months from the onset of symptoms,
and intercourse is compromised by the deformity.
GR
C
Penile length, curvature severity, erectile function (including response to pharmacotherapy

in case of erectile dysfunction) and patient
expectations must be assessed prior to surgery.
Tunical shortening procedures, especially
plication techniques are the first treatment
options for congenital penile curvature and for
Peyronies disease with adequate penile length,
curvature < 60 and absence of special deformities (hour-glass, hinge).
Grafting techniques are the preferred treatment
option for patients with Peyronies disease with
no adequate penile length, curvature > 60 and
presence of special deformities (hour-glass,
hinge).
Penile prosthesis implantation, with or without
any additional procedure (modelling, plication
or grafting), is recommended in Peyronies
disease patients with erectile dysfunction not
responding to pharmacotherapy.
2b
2b
2b
(978-90-79754-83-0), available to all members of the European Association
of Urology at their website, http://www.uroweb.org.
Table 1: Results of surgical treatments for Peyronies

disease (data from different, non-comparable
studies)
Tunical shortening
procedures
Penile shortening
Penile straightening
Persistent or
recurrent curvature
Post-operative
erectile dysfunction
Penile hypoesthesia
Technical
modifications
Tunical
lengthening
procedures
Nesbit
Plication Grafts
4.7-30.8% 41-90%
0-40%
79-100% 58-100% 74-100%
4-26.9%
7.7-10.6% 0-16.7%
0-13%
0-22.9%
0-15%
2-21%
1
0-21.4%
At least 3
0-16.7%
Many types
of grafts and
techniques
used
Figure 1: Treatment algorithm for Peyronies disease

Treatment of Peyronies disease
Discuss natural history of the disease

Reassure patient that Peyronies is a benign disease
Discuss current treatment modalities
Shared decision-making
Active disease
(pain, deformity deterioration, no
calcification on ultrasound)
Stable disease
(no pain, no deformity deterioration,
calcification plaques on ultrasound)
Surgicaltreatment
No ED
Yes
ED
Response
to
treatment
Adequate penis length

Curvature < 60
Absence of special
deformities (hour-glass,
hinge)
Short penis
Curvature > 60
Presence of special
deformities (hour-glass,
hinge)
No
Nesbit or plication
procedures
Tunica lengthening
procedures
Penile
prosthesis
(remodelling,
plaque)
GUIDELINES FOR THE INVESTIGATION

AND TREATMENT OF MALE INFERTILITY
A. Jungwirth, T. Diemer, G.R. Dohle, A. Giwercman,

Z. Kopa, C. Krausz, H. Tournaye
Eur Urol 2002 Oct;42(4):313-22
Eur Urol 2004 Nov;46(5):555-8
Eur Urol 2012 Jan;61(1):159-63
Definition
Infertility is the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy in one year.
(WHO, 1995).
About 15% of couples do not achieve pregnancy within
1 year and seek medical treatment for infertility. Eventually,
less than 5% remain unwillingly childless.
Prognostic factors
The main factors influencing the prognosis in infertility are:
duration of infertility;
primary or secondary infertility;
results of semen analysis;
age and fertility status of the female partner.
As a urogenital expert, the urologist should examine any
male with fertility problems for urogenital abnormalities, so
176 Male Infertility
that appropriate treatment can be given.
Diagnosis
The diagnosis of male fertility must focus on a number of
prevalent disorders (Table 1). Simultaneous assessment of
the female partner is preferable, even if abnormalities are
found in the male, since WHO data show that both male and
female partners have pathological findings in 1 out of 4 couples who consult with fertility problems.
Table 1: Reasons for a reduction in male infertility

Congenital factors (cryptorchidism and testicular
dysgenesis, congenital absence of the vas deferens)
Acquired urogenital abnormalities (obstructions, testicular
torsion, testicular tumour, orchitis)
Urogenital tract infections
Increased scrotal temperature (e.g. due to varicocele)
Endocrine disturbances
Genetic abnormalities
Immunological factors (autoimmune diseases)
Systemic diseases (diabetes, renal and liver insufficiency,
cancer, hemochromatosis)
Exogenous factors (medications, toxins, irradiation)
Lifestyle factors (obesity, smoking, drugs, anabolic steroids)
Idiopathic (4050% of cases)
Semen analysis
Semen analysis forms the basis of important decisions concerning appropriate treatment. Semen analysis should be performed in a laboratory adhering to national quality control
standards (Table 2).
Male Infertility 177
Table 2: Lower reference limits (5th centiles and 95%

confidence intervals) for semen characteristics*
Parameter
Lower reference
limit (95% CI)
Semen volume (mL)
1.5 (1.4-1.7)
Total sperm number (106 per ejaculate) 39 (33-46)
15 (12-16)
Sperm concentration (106 per mL)
Total motility (PR+NP, %)
40 (38-42)
Progressive motility (PR, %)
32 (31-34)
Vitality (live spermatozoa, %)
58 (55-63)
Sperm morphology (normal forms, %) 4 (3.0-4.0)
Other consensus threshold values
> 7.2
pH
Peroxidase-positive leukocytes
< 1.0
(106 per mL)
MAR test (motile spermatozoa with
< 50
bound particles, %)
Immunobead test (motile spermatozoa < 50
with bound beads, %)
> 2.4
Seminal zinc (mol/ejaculate)
> 13
Seminal fructose (mol/ejaculate)
> 20
Seminal neutral glucosidase
(mU/ejaculate)
*WHO Manual for Semen Analysis, 5th edn, 2010.
Frequency of semen analyses
If values are normal according to WHO criteria, one test
should suffice. If the results are abnormal, semen analysis
should be repeated. It is important to distinguish between
oligozoospermia (< 15 million spermatozoa/mL), astheno178 Male Infertility
zoospermia (< 40% motile spermatozoa) and teratozoospermia (< 4% normal forms). Quite often, all three pathologies
occur at the same time, i.e. as oligo-astheno-teratozoospermia
(OAT) syndrome. In extreme cases of OAT syndrome
(< 1 million spermatozoa/mL), just as with azoospermia,
there is an increased incidence of genetic abnormalities
and/or obstruction of the male genital tract.
Hormonal investigation
Endocrine malfunctions are more prevalent in infertile men
than in the general population, but are still quite uncommon.
Hormonal screening can be limited to determining the levels
of follicle stimulating hormone (FSH), luteinizing hormone
(LH) and testosterone in cases of abnormal semen parameters. In men diagnosed with azoospermia or extreme OAT,
it is important to distinguish between obstructive and nonobstructive causes. Criteria with a reasonable predictive value
for non-obstruction are a normal FSH with bilaterally normal
testicular volume. However, 29% of infertile men with a normal FSH appear to have defective spermatogenesis.
Hypergonadotrophic hypogonadism (elevated FSH/LH)
Impaired spermatogenesis associated with elevated levels of
gonadotrophins is a common problem and is due to primary
testicular failure. Causes include:
Congenital Klinefelters syndrome, anorchia, cryptorchidism, testicular dysgenesis, Y chromosome microdeletions
Acquired after orchitis, testicular torsion, testicular
tumour, systemic illness, cytotoxic therapy.
Hypogonadotrophic hypogonadism (deficient FSH/LH)

Low levels of gonadotrophins due to dysfunction of the
pituitary gland or hypothalamus are rare and may occur as a
result of:
Congenital anomalies isolated hypogonadotrophic
hypogonadism (iHH), syndromic KK, Kallmanns syndrome, Prader-Willi syndrome
Acquired anomalies acquired hypothalamic/pituitary
gland diseases (malignant CNS tumours, pituitary adenoma, hyperprolactionaemia, granulomatous illness, hemochromatosis)
Exogenous factors drugs (anabolic steroids, obesity,
irradiation).
If unexplained hypogonadotrophic hypogonadism is present,
the medical examination should include magnetic resonance
imaging (MRI) of the pituitary gland.
Microbiological assessment
Indications for microbiological assessment include abnormal
urine samples, urinary tract infections, male accessory gland
infections (MAGI) and sexually transmitted diseases (STDs).
The clinical implications of white blood cells detected in a
semen sample are as yet undetermined. However, in combination with a small ejaculate volume, this may point to
a (partial) obstruction of the ejaculatory ducts caused by
a (chronic) infection of the prostate or seminal vesicles.
Genital infections may instigate the production of spermatotoxic free oxygen radicals. Neisseria gonorrhoea and
Chlamydia trachomatis infections can also cause obstruction
of the genital tract. Although antibiotic procedures for MAGI
might provide improvement in sperm quality, therapy does

not necessarily increase the probability of conception.
Genetic evaluation
A substantial number of andrological fertility disorders that
used to be described as idiopathic male infertility have a
genetic origin. An extensive family history and karyotype and Y chromosome deletion analysis will detect a number of
these disorders, not only providing a diagnosis, but also enabling appropriate genetic counselling. The latter may be very
important with the advent of intracytoplasmic sperm injection (ICSI), because genetic defects may be transferred and
a balanced translocation of the infertile father may become
unbalanced in the offspring.
Chromosomal abnormalities are more common in men with
OAT and with azoospermia, and karyotyping is recommended in these men both for diagnosis purposes and for genetic
counselling. The most common sex chromosome abnormality is Klinefelters syndrome (47, XXY), which affects around
14% of men diagnosed with azoospermia. Klinefelters syndrome is characterized by hypergonadotrophic hypogonadism which may be associated with eunuchoid features and/or
gynaecomastia. Both testicles are very small due to extensive
tubular sclerosis. In around 60% of all patients, testosterone
levels decrease with age requiring androgen replacement.
Furthermore, chromosome translocations and deletions can
be found, which may be hereditary and cause habitual abortion and congenital malformations in the offspring. In cases
of azoospermia or severe OAT, there may be deletions in the
azoospermic factor (AZF) region of the Y chromosome and

testing is advised. The prevalence of Y deletions is considerable (around 5%) in this group of patients. The presence of a
Y deletion means that the defect will be passed to sons, who
will then also be be affected by spermatogenic disturbances
or failure.
When performing ICSI with surgically retrieved sperm or
ejaculated spermatozoa, based on a diagnosis of congenital
bilateral/unilateral absence of the vas deferens (CAVD), both
the male and the female partner should be tested for mutations in the cystic fibrosis transmembrane regulator (CFTR)
gene. Apart from causing cystic fibrosis (CF), this gene is
also associated with CAVD; 85% of all males diagnosed with
CAVD also test positive for two CFTR-gene mutations when
the entire gene is sequenced. In cases where the partner is
a carrier of a CFTR mutation, depending on the mutation
involved, there is a 25% chance of a child with CF or CAVD.
Genetic counselling is mandatory in these cases.
Ultrasonography
Ultrasonography is a useful tool for locating intrascrotal
defects. Colour Doppler ultrasound of the scrotum can detect
a varicocele in around 30% of subfertile males. Testicular
tumours can be found in 0.5%, and testicular microcalcifications (a potentially premalignant condition) are detected in
around 25% of subfertile males, especially patients diagnosed with a history of cryptorchidism. Transrectal ultrasonography (TRUS) is indicated in men with a low volume of
ejaculate (<1.5 mL) to exclude obstruction of the ejaculatory
ducts caused by a midline prostatic cyst or stenosis of the

ejaculatory ducts.
Testicular biopsy
Testicular biopsy is usually performed as part of a therapeutic process in azoospermic patients (testicular sperm retrieval) who decide to undergo ICSI. Indications for performing a
diagnostic testicular biopsy could be azoospermia or extreme
OAT, in the presence of a normal testicular volume and
normal FSH levels. The biopsy is aimed at differentiating
between testicular insufficiency and obstruction of the male
genital tract. It is advised that, during the procedure, tissue
that contains spermatozoa is cryopreserved for future ICSI
attempts.
In addition, testicular biopsies are performed to detect carcinoma in situ of the testis in infertile men with testicular
microcalcifications and risk factors for testicular cancer
(i.e. male infertility, cryptorchidism, history of a testicular
tumour, testicular atrophy).
Pathological classifications are:
Absence of seminiferous tubules (tubular sclerosis)
Presence of sertoli cells only (sertoli cell only syndrome)
Maturation arrest spermatogenesis arrested at different
stages (spermatogonia, spermatocytes or spermatides)
Hypospermatogenesis all cell types up to spermatozo are
present, but there is a distinct decline in the number of
reproducing spermatogonia.
Treatment
Counselling
Lifestyle factors can impair semen quality, e.g. heavy
smoking, alcohol abuse, use of anabolic steroids, extreme
sports (marathon training, excessive strength sports), and
an increase in scrotal temperature through thermal underwear, sauna or hot tub use, or occupational exposure to heat
sources. A considerable number of drugs can affect spermatogenesis.
Medical (hormonal) treatment
Antioxidant treatment (folic acid, vitamin E, zinc, selenium) have a positive influence on semen quality and some
improvement of spontaneous pregnancy rates. No studies
have confirmed that hormonal therapies, such as human
menopausal gonadotrophin (HMG)/human chorionic gonadotrophin (HCG), androgen, anti-oestrogens (clomiphene
and tamoxifen), prolactin inhibitors (bromocriptine) and
steroids, have improved pregnancy rates in men with idiopathic OAT. However, some primarily endocrinological
pathologies can be treated medically, including:
Low testosterone: clomiphene citrate 50 mg/day or
tamoxifen 20 mg/day
Hypogonadotrophic hypogonadism: start HCG 1500 IU
subcutaneously 3 times per week, and add HMG or FSH
75150 IU intramuscularly 3 times per week, until spermatogenesis occurs
Hyperprolactinaemia: dopamine agonists.
In patients with sperm autoantibodies, high-dose corticos184 Male Infertility
teroids, although effective, are not recommended because of

serious side-effects.
Surgical treatment
Varicocele
The treatment of varicocele is a controversial subject, mainly
based on whether there is an actual need to treat varicocele
in infertile men. There is evidence of improved semen parameters after successful varicocele treatment. Current information supports the hypothesis that in some men, the presence
of varicocele is associated with progressive testicular damage
from adolescence onwards and consequent reduction in fertility. Although treatment of varicocele in adolescents may be
effective, there is a significant risk of over-treatment. In cases
of normal semen analysis and in men with a subclinical varicocele, there appears to be no benefit from treatment compared with observation. Varicocele repair, however, seems
effective in couples in whom the men hasoligozoospermia, a
clinical varicocele and otherwise unexplained infertility.
Microsurgery/vasovasostomy and epididymovasostomy
Only urologists with experience in microsurgery should
undertake these procedures using an operating microscope.
The likelihood of initiating pregnancy is inversely proportional to the obstruction interval and becomes less than 50%
after 8 years. Other important prognostic factors are the
quality of the semen after the procedure and the partners
age. In approximately 15% of men who have undergone a
successful vasovasostomy, sperm quality deteriorates to the
level of azoospermia or extreme oligospermia within 1 year.
Sometimes an epididymal obstruction coexists, especially

in men with a long interval between vasectomy and vasovasostomy. In these men a vaso-epididymostomy is indicated.
Considering that a vaso-epididymostomy has a limited effect
on pregnancy rates (2030%), it is advisable to combine
this procedure with microsurgical epididymal sperm aspiration (MESA), and cryopreserve the harvested spermatozoa
for ICSI. The indications for vaso-epididymostomy include
obstructions at the level of the epididymis in the presence
of a normal spermatogenesis (testicular biopsy). Poor sperm
quality and sometimes sperm antibodies after successful
vasectomy repair may prevent spontaneous pregnancy and
assisted reproduction is indicated.
MESA/TESE
MESA in combination with ICSI is indicated in men with
obstructive azoospermia when reconstruction (vasovasostomy, vaso-epididymostomy) cannot be performed or is unsuccessful. An alternative would be percutaneous aspiration of
spermatozoa from the caput epididymis (PESA). If a MESA
or PESA procedure does not produce spermatozoa, testicular
sperm extraction (TESE) can be applied. In about 5060% of
men with non-obstructive azoospermia (NOA), spermatozoa
can be found in the testis. Some authors recommend taking
several testicular samples, while others advocate microsurgical harvesting of spermatozoa. So far, no clinical or laboratory parameter has been shown to be useful in predicting
sperm harvesting in men with NOA. In case of AZFa and
AZFb microdeletions, no spermatozoa can be retrieved.
Transurethral incision of ejaculatory ducts or midline prostatic

cyst
Distal obstructions of the genital tract are commonly caused
by infections of the prostatic urethra and the accessory
glands or by a cyst in the midline of the prostate. Treatment
of the obstruction by transurethral incision of the cyst or the
ejaculatory ducts (TURED) may lead to an increase in semen
quality and, occasionally, spontaneous pregnancy. Long-term
results, however, are disappointing.
Disorders of ejaculation
Retrograde ejaculation and anejaculation can occur:
In neurological diseases, e.g. multiple sclerosis, diabetes
mellitus (neuropathy) and spinal cord injuries
Following prostate surgery, bladder neck surgery, sympathectomy and retroperitoneal surgery, e.g. lymph node
dissections for testicular tumours
During antidepressant therapy.
Often, no cause for retrograde ejaculation can be found.
The diagnosis is based on the medical history and laboratory microscopic assessment of the post-ejaculate urine.
Retrograde ejaculation should also be suspected if the
ejaculate volume is very low (partial retrograde ejaculation).
Treatment of retrograde ejaculation is basically aimed at
removing the cause of the disorder or harvesting spermatozoa from the urine after orgasm.
Anejaculation can be treated by vibrostimulation or electroejaculation techniques. It is possible to induce ejaculation in
around 90% of patients with spinal cord injuries. However,
the semen quality is often poor with a low number of motile

spermatozoa and increased rates of DNA fragmentation. This
accounts for the disappointing results of assisted reproduction techniques in these men. Testicular sperm extraction
(TESE), in-vitro fertiliation and ICSI are often required.
of Urology at their website - http://www.uroweb.org.
GUIDELINES ON
Male Hypogonadism
G.R. Dohle, S. Arver, C. Bettocchi, S. Kliesch, M. Punab,
W. de Ronde
Introduction
Male hypogonadism is a clinical syndrome caused by androgen deficiency. It may adversely affect multiple organ functions and quality of life. Androgens play a crucial role in
the development and maintenance of male reproductive and
sexual functions. Low levels of circulating androgens can
cause disturbances in male sexual development, resulting
in congenital abnormalities of the male reproductive tract.
Later in life, this may cause reduced fertility, sexual dysfunction, decreased muscle formation and bone mineralisation,
disturbances of fat metabolism, and cognitive dysfunction.
Testosterone levels decrease as a process of ageing: signs and
symptoms caused by this decline can be considered a normal part of ageing. However, low testosterone levels are also
associated with several chronic diseases, and symptomatic
patients may benefit from testosterone treatment.
Androgen deficiency increases with age; an annual decline
in circulating testosterone of 0.4-2.0% has been reported. In
middle-aged men, the incidence was found to be 6%. It is
more prevalent in older men, in men with obesity, those with
co-morbidities, and in men with a poor health status.
Male Hypogonadism 189
Aetiology and forms

Male hypogonadism can be classified in 4 forms:
1. Primary forms caused by testicular insufficiency;
2. Secondary forms caused by hypothalamic-pituitary dysfunction;
3. Late onset hypogonadism;
4. Male hypogonadism due to androgen receptor insensitivity.
The main causes of these different forms of hypogonadism
are highlighted in Table 1.
The type of hypogonadism has to be differentiated, as this
has implications for patient evaluation and treatment and
enables identification of patients with associated health
problems.
Table 1: Different forms of male hypogonadism and

main causes
Primary forms
(testicular insufficiency)
Congenital forms
Acuired forms
190 Male Hypogonadism
Main causes
Klinefelter syndrome
Testicular dysgenesis
(cryptorchidism)
Congenital anorchia
Testicular malignancy
Orchitis
Medications (chemotherapy)
Systemic diseases
Acuired anorchia
Secondary forms
(hypothalamic-pituitary
dysfunctions)
Congenital forms
Acuired forms
Late onset hypogonadism

(Combined testicular and
hypothalamic pituitary
insucfficiency)
Androgen receptor
insensitivity
Main causes
Kallmann syndrome
Idiopathic
hypogonadotrophic
hypogonadism (IHH)
Pituitary tumour
(prolactinoma)
Drugs
Systemic disease (renal
failure, hemochromatosis,
hypothyroidism, trauma,
infections)
Abuse of anabolic steroids
Morbid obesity
Radiotherapy
Ageing
Obesity
Chronic diseases
Poor health status
Partial androgen insensitivity
syndrome (PAIS)
Diagnosis
The diagnosis of male hypogonadism is based on clinical
symptoms and signs of androgen deficiency (Table 2 and 3),
together with consistently low serum testosterone levels.
Table 2: Signs and symptoms suggesting prepubertalonset hypogonadism

Small testes
Cryptorchidism
Gynaecomastia
High voice
Unclosed epiphyses
Linear growth into adulthood
Eunuchoid habitus
Sparse body/facial hair
Infertility
Low bone mass
Sarcopenia
Reduced sexual desire/activity
Table 3: Signs and symptoms associated with lateonset hypogonadism

Loss of libido
Erectile dysfunction
Sarcopenia
Low bone mass
Depressive thoughts
Changes in mood, fatigue and anger
Sleep disturbances
Loss of body hair
Hot flushes
Loss of vigour
Insulin resistance
Metabolic syndrome
Visceral obesity
Gynaecomastia
Diminished cognitive functions
Routine screening for testosterone deficiency is not indicated.
However, testosterone assessment should be done in men
with:
Pituitary mass, following radiation involving the sellar
region and other diseases in the hypothalamic and sellar
region;
End-stage renal disease receiving haemodialysis;
Treatment with medications that cause suppression of testosterone levels e.g. corticosteroids and opiates;
Moderate to severe chronic obstructive lung disease;
Infertility;
Osteoporosis or low-trauma fractures;
Human immunodeficiency virus (HIV) infection with sarcopenia;
Type 2 diabetes.
Acquired hypogonadotropic hypogonadism (secondary
forms) can be caused by some drugs, hormones, anabolic
steroids and by tumours of the pituitary gland. Imaging (CT
scan or MRI) of the sellar region and complete endocrine
work-up is requested when a pituitary tumour is suspected.
Recommendations for screening
GR
Screening for testosterone deficiency is only recomC
mended in adult men with consistent and preferably
multiple signs and symptoms, listed in Tables 2 and 3.
Adult men with established severe hypogonadism

B
should be screened for concomitant osteoporosis.
Total testosterone assessment should be repeated at
A
least on two occasions with a reliable method.
- In men with total testosterone levels close to the
lower normal range (8-12 nmol/l), the free testosterone level should be measured to strengthen the
laboratory assessment.
- In men with suspected or known abnormal sex
hormone-binding globulin (SHBG) levels, free testosterone should also be included.
Treatment
The aim of treatment is to restore testosterone levels to the
physiological range and thereby improve the patients quality
of life. Indications and contraindications are listed in Tables
4 and 5.
Table 4: Indications for testosterone treatment

dult men with consistent and preferably multiple signs
A
and symptoms of hypogonadism (listed in Tables 2 and 3)
and low testosterone
Delayed puberty (idiopathic, Kallmann syndrome)
Klinefelter syndrome with hypogonadism
Sexual dysfunction and low testosterone
Low muscle strength and bone mass in hypogonadism
Hypopituitarism
Testicular insufficiency and symptomatic hypogonadism
Table 5: Contraindications against testosterone

treatment
rostate cancer
P
Prostate-specific antigen (PSA) > 4 ng/mL
Male breast cancer
Severe sleep apnoea
Male infertility
Haematocrit > 50%
Severe lower urinary tract symptoms due to benign prostatic enlargement
Choice of treatment
Testosterone replacement therapy (TRT) is safe and effective
and the agents are available as oral preparations, intramuscular injections, and transdermal gel or patches (Table 6).
Table 6: Testosterone preparations for replacement

therapy
Formulation
Testosterone
undecanoate
Administration Advantages
Oral; 2-6 cps
Absorbed
every 6 h
through the
lymphatic
system, with
consequent
reduction of
liver involvement
Disadvantages
Variable levels
of testosterone
above and
below the
mid-range.
Need for
several doses
per day with
intake of fatty
food
Short-acting
preparation
that allows
drug withdrawal in case
of onset of
side effects
Short-acting
preparation
that allows
drug withdrawal in case
of onset of
side effects
Steady-state
testosterone
levels without
fluctuation
Testosterone
cypionate
Intramuscular;
one injection every 2-3
weeks
Testosterone
enanthate
Intramuscular;
one injection every 2-3
weeks
Testosterone
undecanoate
Intramuscular;
one injection
every 10-14
weeks
Transdermal
testosterone
Gel or skin
patches; daily
application
Steady-state
testosterone
level without
fluctuation
Sublingual
testosterone
Sublingual;
daily doses
Rapid absorption and

achievement
of physiological serum level
of testosterone
Possible fluctuation of
testosterone
levels
Possible fluctuation of
testosterone
levels
Long-acting
preparation
that cannot
allow drug
withdrawal in
case of onset
of side effects
Skin irritation
at the site of
application
and risk of
interpersonal
transfer
Local irritation
Buccal testosterone
Buccal tablet;
two doses per
day
Subdermal
depots
Subdermal
implant every
5-7 months
Rapid absorption and

achievement
of physiological serum level
of testosterone
Long duration
and constant
serum testosterone level
Irritation and
pain at the site
of application
Risk of infection and

extrusion of
the implants
In patients with secondary hypogonadism, anti-oestrogens

or hormonal stimulation with hCG and FSH or alternatively
GnRH can restore testosterone production.
Recommendations
GR
The patient should be fully informed about expected A
benefits and side effects of each treatment option. The
selection of the preparation should be a joint decision
by an informed patient and the physician.
Short-acting preparations may initially be preferred to B
long-acting depot administration when starting treatment. Patients can switch to a long-acting depot if
preferred and side effects are absent or minimal.
Human chorionic gonadotrophin (hCG) treatment
B
can only be recommended for hypogonadal patients
who are receiving simultaneous fertility treatment.
Risk factors in testosterone treatment

C
ase reports and small cohort studies point to a possible
correlation between TRT and the onset of breast cancer,
but there is as yet a lack of strong evidence for this relationship.

Randomised controlled trials support the hypothesis that
TRT does not result in changes in prostatic histology.
However, there are not yet data available that show longterm prostatic safety of TRT.
Testosterone therapy is not related to the development
of de novo cardiovascular events. However, patients with
severe cardiovascular diseases should be screened first by
a cardiologist before TRT is initiated.
Recommendations for initiation of treatment

Haematological, cardiovascular, breast and prostatic
assessment should be performed before the start of
treatment.
Men with severe cardiovascular co-morbidity should
be assessed by a cardiologist before TRT is initiated
and there should be close cardiovascular monitoring
during TRT.
Prostate health should be assessed by digital rectal
examination (DRE) and PSA before the start of TRT.
In patients treated for localised prostate cancer
and without signs of prostate cancer recurrence,
testosterone therapy should not start before at least 1
year of follow-up.
Recommendations for monitoring

The response to treatment (symptoms and
testosterone serum levels) should be assessed 3, 6 and
12 months after the onset of treatment, and thereafter
annually.
GR
A
A
C
GR
C
In men with an abnormal bone mineral density

(BMD), BMD measurements should be repeated 6
and 12 months after the start of TRT and thereafter
annually.
Haematocrit should be monitored at 3, 6 and 12
months and thereafter annually. The testosterone
dosage should be decreased, or therapy discontinued
if the haematocrit increases above normal levels.
Prostate health should be monitored by PSA testing at
3, 6 and 12 months and thereafter annually.
Routine screening of potential cardiovascular side
effects is not indicated in men receiving TRT.
C
A
of Urology at their website, http://www.uroweb.org.
GUIDELINEs ON URINARY
INCONTINENCE
(Complete text update February 2012)
M.G. Lucas (chairman), J.L.H.R. Bosch, F. Cruz,

D.J.M.K. de Ridder, T.B. Madden, A. Nambiar, A. Neisius,
R.S. Pickard, A. Tubaro, W.H. Turner
This pocket version aims to synthesise the important clinical messages described in the full text and is presented as
a series of evidence summaries and graded action based
recommendations, which follow the standard for levels of
evidence used by the EAU (see Introduction chapter).
The grades of recommendation aim to make it clear what
the clinician should or should not do in clinical practice, not
merely to comment on what they might do.
Recommendations have been deliberately written as actionbased sentences. The following words or phrases are used
consistently throughout the Guidelines, as follows.
Consider an action. This word is used when there is not
enough evidence to say whether the action causes benefit or risk to the patient. However, in the opinion of the
Panel, the action may be justified in some circumstances.
Action is optional.
Offer an action. This word is used when there is good evidence to suggest that the action is effective, or that, in the
200 Urinary Incontinence
opinion of the Panel, it is the best action. Action is advisable.

Carry out (perform) an action. Do something. This
phrase is used when there is strong evidence that this is
the only best action in a certain clinical situation. Action
is mandatory.
Avoid an action. This phrase is used when there is highlevel evidence that the action is either ineffective or is
harmful to the patient. Action is contraindicated.
The Panel has tried to avoid extensive narrative text. Instead,
algorithms are presented for both initial and specialised management of men and women with non-neurogenic UI. Each
decision node of these algorithms is clearly linked back to
the relevant evidence and recommendations.
ASSESSMENT AND DIAGNOSIS

History and Physical Examination
Although there is no evidence to support this, there is absolute consensus of expert opinion that this is an essential step.
Recommendations 1
Take a history to include the following;
Type of incontinence (stress, urge or mixed)
Timing and severity
Any associated urinary symptoms
Obstetric and gynaecological history
Any comorbidities
Medication review
GR
A*
Urinary Incontinence 201
A*
Do a physical examination to include:
Abdominal exam to detect bladder enlargement or
abdominal/pelvic mass
Perineal examination
Digital vaginal or rectal examination
Assess oestrogen status of woman
Assess voluntary pelvic floor contraction
A*
Consider early referral to specialist if:
UI associated with pain
Haematuria
History of recurrent UTI
Previous pelvic surgery or radiotherapy
Constant leak suspicious of fistula
Any voiding difficulty
Suspicion of neurological disease
* Given Grade A because, despite an absence of evidence, expert
opinion assigns absolute importance to these steps
Questionnaires
Recommendations 2
GR
Healthcare professionals should be aware that the use C
of questionnaires and PROMs has not been shown
to influence patient outcome in UI due to the lack of
specific research in this area
Voiding diaries
Recommendations 3
Voiding diaries should be used in urinary incontinence to evaluate co-existing storage and voiding
dysfunction in clinical practice and in research
A diary duration of between 3 and 7 days is recommended
Urinalysis and UTI

Recommendations 4
Do urinalysis as a part of the initial assessment of a
patient with urinary incontinence
In a patient with urinary incontinence, treat a symptomatic urinary tract infection appropriately (see
EAU Guidelines on Urological Infections)
Do not treat asymptomatic bacteriuria in elderly
patients to improve urinary incontinence
Post-voiding residual volume

Recommendations 5
Post-voiding residual should be measured by ultrasound
Measure post-voiding residual in patients with urinary incontinence who have voiding dysfunction
Measure post-voiding residual when assessing
patients with complicated urinary incontinence
Post-voiding residual should be monitored in patients
receiving treatments that may cause or worsen voiding dysfunction
GR
A
GR
A
A
GR
A
B
C
B
Urodynamics
Recommendations 6
(NB: These refer only to neurologically intact adults
with urinary incontinence)
Clinicians carrying out urodynamics in patients with
urinary incontinence should:
Ensure that the test replicates patients symptoms
Interpret results in context of the clinical problem
Check recordings for quality control
Remember there may be physiological variability
within the same individual
Advise patients that the results of urodynamics may
be useful in discussing treatment options, although
there is limited evidence that performing urodynamics will alter the outcome of treatment for urinary
incontinence
Do not routinely carry out urodynamics when offering conservative treatment for urinary incontinence
Perform urodynamics if the findings may change the
choice of surgical treatment
Perform urodynamics prior to surgery for urinary
incontinence if there are either symptoms of overactive bladder, a history of previous surgery or a suspicion of voiding difficulty
Do not routinely carry out urethral pressure profilometry
GR
B
C
C
Pad testing
A well-designed continence pad will contain any urine leaked
within a period of time and this has therefore been used as
a way of quantifying leakage. Although the International
Continence Society has attempted to standardize pad testing,
there remain differences in the way patients are instructed to

undertake activity during the test.
Recommendations 7
GR
Use a pad test when quantification of urinary inconti- C
nence is required
Use repeat pad test if objective treatment outcome
C
measure is required
Imaging
Recommendation 8
GR
Do not routinely carry out imaging of the upper
A
or lower urinary tract as part of the assessment of
uncomplicated stress urinary incontinence in women
CONSERVATIVE TREATMENT
Conventional medical practice encourages the use of simple,
relatively harmless, interventions before resort to those associated with higher risks.
Simple Medical interventions

Correction of Underlying disease/cognitive impairment
Numerous conditions exacerbate UI or make it more likely to
occur, whether or not they play any part in the pathophysiology of leakage. These conditions include:
cardiac failure
chronic renal failure
diabetes
chronic obstructive pulmonary disease
neurological disorders
stroke
dementia
multiple sclerosis
general cognitive impairment
sleep disturbances e.g. sleep apnoea.
Adjustment of medication
There is very little evidence of benefit from the adjustment
of medication. There is also a theoretical risk, at least, that
stopping or altering medication may bring with it more harm
than good.
Recommendations 9
GR
Take a drug history from all patients with urinary
A
incontinence
Inform women with urinary incontinence that begins A
or worsens after starting systemic oestrogen replacement therapy that it may cause urinary incontinence
Review any new medication associated with the
C
development or worsening of urinary incontinence
Constipation
Several studies have shown strong associations between
constipation, urinary incontinence and overactive bladder.
Constipation can be improved by behavioural and medical
treatments.
Recommendations 10
For adults with urinary incontinence, treat co-existing constipation
GR
C
Containment (pads etc)

Recommendations 11
Offer pads when containment of urinary incontinence is needed
Adapt the choice of pad to the type and severity of
urinary incontinence and the patients needs
Offer catheterisation to manage urinary incontinence
when no other treatments can be considered
Offer condom catheters to men with urinary incontinence without significant residual urine
Offer to teach intermittent catheterisation to manage
urinary incontinence associated with retention of
urine
Do not routinely offer intravaginal devices as treatment for incontinence
Do not use penile clamps for control of urinary
incontinence in men
GR
B
A
B
A
A
B
A
Lifestyle Changes
Examples of lifestyle factors that may be associated with
incontinence include obesity, smoking, level of physical
activity and diet. It may therefore be possible to improve urinary incontinence by beginning lifestyle interventions, such
as weight loss, fluid restriction, reduction of caffeine or alcohol intake, limiting heavy activity and stopping smoking.
Recommendations 12
Encourage obese women suffering from any urinary
incontinence to lose weight (> 5%)
Advise adults with urinary incontinence that reducing caffeine intake may improve symptoms of urgency and frequency but not incontinence
Patients with abnormally high or abnormally low
fluid intake should be advised to modify their fluid
intake appropriately
Counsel female athletes experiencing urinary incontinence with intense physical activity that it will not
predispose to urinary incontinence in later life
Patients with urinary incontinence who smoke
should be given smoking cessation advice in line
with good medical practice although there is no definite effect on urinary incontinence
Behavioural and physical therapies

Recommendations 13
Offer supervised pelvic floor muscle training lasting
at least 3 months, as a first-line therapy to women
with stress or mixed urinary incontinence
Pelvic floor muscle training programmes should be as
intensive as possible
Consider using biofeedback as an adjunct in women
with stress urinary incontinence
Offer supervised pelvic floor muscle training to continent women in their first pregnancy to help prevent
incontinence in the postnatal period
GR
A
B
GR
A
A
A
A
Offer instruction on pelvic floor exercises to men

undergoing radical prostatectomy to speed recovery
of urinary incontinence
Offer bladder training as a first-line therapy to adults
with urgency urinary incontinence or mixed urinary
incontinence
Offer timed voiding to adults with urinary incontinence, who are cognitively impaired
Do not offer electrical stimulation with surface electrodes (skin, vaginal, anal) alone for the treatment of
urinary incontinence
Do not offer magnetic stimulation for the treatment
of urinary incontinence or overactive bladder in adult
women
Offer posterior tibial nerve stimulation to women
with urgency urinary incontinence who cannot tolerate anticholinergic medication
A
A
DRUG TREATMENT OF URINARY INCONTINENCE

Antimuscarinics
Recommendations 14
GR
Offer instant release or extended release formulations A
of antimuscarinic drugs as initial drug therapy for
adults with urgency urinary incontinence
If instant release formulations of antimuscarinic
A
drugs are unsuccessful for adults with urgency urinary incontinence, offer extended release formulations or longer-acting antimuscarinic agents
Consider using transdermal oxybutynin if oral
B
antimuscarinic agents cannot be tolerated due to dry
mouth
Offer and encourage early review (of efficacy and side

effects) of patients on antimuscarinic medication for
urgency urinary incontinence (< 30 days)
When prescribing antimuscarinic drugs to elderly
patients, be aware of the risk of cognitive side effects,
especially in those receiving cholinesterase inhibitors
Avoid using oxybutynin instant release in patients
who are at risk of cognitive dysfunction
Consider use of trospium chloride in patients known
to have cognitive dysfunction
Use solifenacin, tolterodine and darifenacin with caution in patients with cognitive dysfunction
Do an objective assessment of mental function before
treating patients whose cognitive function may be at
risk
Check mental function in patients on antimuscarinic
medication if they are at risk of cognitive dysfunction
Duloxetine
Recommendations 15
Duloxetine should not be offered to women or men
who are seeking a cure for their incontinence
Duloxetine can be offered to women or men who
are seeking temporary improvement in incontinence
symptoms
Duloxetine should be initiated using dose titration
because of high adverse effect rates
A
B
B
C
GR
A
A
Intravaginal Oestrogen
Recommendations 16
GR
Women using systemic oestrogen should be counA
selled that they have an increased risk for developing
urinary incontinence or worsening of their existing
incontinence
Offer post-menopausal women with urinary inconA
tinence local oestrogen therapy, although the ideal
duration of therapy and best delivery method are
unknown
Advise post-menopausal women who are taking oral B
oestrogens that they have an increased risk for developing urinary incontinence or worsening of their
existing urinary incontinence
Desmopressin
Recommendations 17
GR
Offer desmopressin to patients requiring occasional
B
short-term relief from urinary incontinence, inform
them that this drug is not licensed for this indication
Do not use desmopressin for long-term control of
A
SURGICAL TREATMENT
Generic principles of surgery:
Always discuss the purpose of surgery and the likely benefits and risks, with the patient and/or carers
Explain alternative approaches even if they are not available locally
Surgeons should be properly trained to do these proceUrinary Incontinence 211
dures and perform adequate numbers to maintain expertise

Surgeons should be able to report their own outcomes for
any operation they offer and share this information with
their patient
Recommendations 18
(Surgery for women with uncomplicated stress urinary
incontinence)
Offer the mid-urethral sling to women with uncomplicated stress urinary incontinence as the preferred
surgical intervention whenever available
Offer colposuspension (open or laparoscopic) or
autologous fascial sling to women with stress urinary
incontinence if mid-urethral sling cannot be considered
Warn women who are being offered a retropubic
insertion synthetic sling about the relatively higher
risk of peri-operative complications compared to
transobturator insertion
Warn women who are being offered transobturator
insertion of mid-urethral sling about the higher risk
of pain and dyspareunia in the longer term
Warn women undergoing autologous fascial sling
that there is a high risk of voiding difficulty and the
need to perform clean intermittent self-catheterisation; ensure they are willing and able to do so.
Do a cystoscopy as part of retropubic insertion of
a mid-urethral sling, or if difficulty is encountered
during transobturator sling insertion, or if there is a
significant cystocoele
GR
Women being offered a single-incision sling device

for which an evidence base exists, should be warned
that short-term efficacy is inferior to standard midurethral slings and that long-term efficacy remains
uncertain
Only offer single-incision sling devices, for which
there is no level 1 evidence base, as part of a structured research programme
Only offer adjustable mid-urethral sling as a primary
surgical treatment for stress urinary incontinence as
part of a structured research programme
Do not offer bulking agents to women who are seeking a permanent cure for stress urinary incontinence
Complicated Stress UI in women

Recommendations 19
GR
(Surgery for complicated stress urinary incontinence
in women)
The choice of surgery for recurrent stress urinary
C
incontinence should be based on careful evaluation
of the individual patient
Women should be warned that the outcome of secC
ond-line surgical procedures is likely to be inferior to
first-line treatment, both in terms of reduced benefit
and increased risk of harm
C
Offer implantation of AUS or ACT as an option for
women with complicated stress urinary incontinence
if they are available and appropriate monitoring of
outcome is in place
Warn women receiving AUS or ACT that there is a

high risk of mechanical failure or a need for explantation
AUS = Artificial Urinary Sphincter; ACT = Adjustable

Compression Therapy
Men with Stress UI

Recommendations 20
(Surgical treatment of men with stress urinary
incontinence)
Only offer bulking agents to men with mild postprostatectomy incontinence who desire temporary
relief of UI symptoms
Do not offer bulking agents to men with severe postprostatectomy incontinence
Offer fixed slings to men with mild-to-moderate postprostatectomy incontinence
Warn men that severe incontinence, prior pelvic radiotherapy or urethral stricture surgery, may worsen
the outcome of fixed male sling surgery
Offer AUS to men with persistent (more than 6
months) moderate-to-severe post-prostatectomy
incontinence that has not responded to conservative
management
Warn about the long-term risk of failure and need for
revision when counselling men for insertion of AUS
Only offer the non-circumferential compression
device (ProACT) for men with post-prostatectomy
incontinence if arrangements for monitoring of outcome are in place
GR
C
B
C
C
C
Warn men considering a non-circumferential comC

pression device (ProACT) that there is a high risk
of failure and subsequent explantation
Do not offer non-circumferential compression device C
(ProACT) to men who have had pelvic radiotherapy
AUS = Artifical urinary sphincter
Surgical interventions for Refractory Detrusor

Overactivity
Intravesical Botulinum Toxin injection
Recommendations 21
GR
Offer botulinum toxin A intravesical injections to
A
patients with urgency urinary incontinence refractory
to antimuscarinic therapy
Warn patients of the possible need to self-catheterise A
and the associated risk of urinary tract infection;
ensure that they are willing and able to do so
Patients should also be warned of the licensing status A
of botulinum toxin A, and that the long-term effects
remain unknown
Sacral nerve stimulation (neuromodulation)

Recommendation 22
GR
If available, offer patients with urgency urinary
A
incontinence that is refractory to conservative
therapy, the opportunity to be treated by sacral nerve
neuromodulation before bladder augmentation or
urinary diversion is considered
Augmentation Cystoplasty / Urinary Diversion

Recommendations 23
Only offer augmentation cystoplasty to patients with
detrusor overactivity incontinence who have failed
conservative therapy, in whom the possibility of
botulinum toxin and sacral nerve stimulation has
been discussed
Warn patients undergoing augmentation cystoplasty
of the high risk of having to perform clean intermittent self-catheterisation; ensure they are willing and
able to do so
Do not offer detrusor myectomy as a treatment for
Only offer urinary diversion to patients who have
failed less invasive therapies for the treatment of urinary incontinence and who will accept a stoma
Warn patients undergoing augmentation cystoplasty
or urinary diversion of the high risk of short-term
and long-term complications, and the possible small
risk of malignancy
Life-long follow-up is recommended for patients who
have undergone augmentation cystoplasty or urinary
diversion
GR
C
C
C
Treatment of Mixed Urinary Incontinence

Recommendations 24
Treat the most bothersome symptom first in patients
with mixed urinary incontinence
Warn patients with mixed urinary incontinence that
the chance of success of pelvic floor muscle training
is less satisfactory than for stress urinary incontinence alone
Offer antimuscarinic drugs to patients with urgepredominant mixed urinary incontinence
Warn patients with mixed urinary incontinence that
surgery is less likely to be successful than surgery in
patients with stress urinary incontinence alone
GR
C
B
A
A
This short text is based on the more comprehensive EAU guidelines (ISBN
978-90-79754-09-0), available to all members of the European Association of
Urology at their website - http://www.uroweb.org.
continued on page 205
Initial assessment
History
Physical examiniation
Questionnaire optional
Voiding diary
Urinalysis
Post void residual
if voiding difficulty
Pad test if quantification
of leakage is desired
rec 5
rec 7
GB
rec 1
rec 1
rec 2
rec 3
rec 4
GC
GA
GA
GC
GB
GA
Female presenting with Urinary

Incontinence
Haematuria
Pain
Recurrent UTI
Grade 3 or symptomatic prolapse
Previous pelvic radiotherapy
Previous surgery for UI (go to bottom
of pathway)
Pelvic mass
Suspicion of fistula
Reasons for
specialist
Referral
(rec 1)
Mixed
Incontinence
Rec 24
Supervised, intensive PFMT

+/- Biofeedback GA rec 13
+/- Bladder training GB recs 13&24
GC recs 9, 10, 12
GA rec 12
GC
GB rec 11
GB rec 12
GA rec 16
Urgency
Incontinence
Anti-muscarinics
GA recs 14 + 24
Consider PTNS
GB rec 13
Bladder training GB rec 13
Advise on bowels, drugs, co-morbidity, fluid intake

Advise on weight loss
Consider intervention related to cognitive impairment (scheduled voiding)
Offer pads if needed
Consider reducing caffeine intake
Consider topical oestrogen for post-menopausal women
Stress
Incontinence
Female
Discuss management

Mixed
Incontinence
Rec 24
Provide information on
pelvic floor excersie
GB rec 13
Anti-muscarinics
GA recs 14 + 24
Consider PTNS
GB rec 13
GC recs 9, 10, 12
GA rec 12
GC
GB rec 11
GB rec 12
Urgency
Incontinence
Bladder training
GB rec 13
Advise on bowels, drugs, co-morbidity, fluid intake

Advise on weight loss
Consider intervention related to cognitive impairment (scheduled voiding)
Offer pads if needed
Consider reducing caffeine intake
Stress
Incontinence
Male
Discuss management
Initial assessment
History
Physical examiniation
Questionnaire optional
Voiding diary
Urinalysis
Post void residual
if voiding difficulty
Pad test if quantification
of leakage is desired
rec 1
rec 1
rec 2
rec 3
rec 4
rec 5
rec 7
GA
GA
GC
GB
GA
GB
GC
Male presenting with Urinary

Incontinence
See rec 1
Haematuria
Pain
Recurrent UTI
Previous pelvic radiotherapy
Abnormal DRE
Findings suspicious of voiding
dysfunction
Reasons for
specialist
Referral

Stress
predominant
Re-evaluate patient and

consider second-line
surgery
GC rec 19
Failure
Urgency
Incontinence
Discuss bladder augmentation on

urinary diversion
GA rec 23
Offer the
opportunity
for SNS GA rec 22
GA rec 6
Urgency
predominant
Offer Botulinum
toxin A or the
opportunity for
SNS GA rec 21
Mixed
Incontinence
See Rec 24
Re-evaluate and
re-enter algorithm
at appropriate
stage
Offer fascial sling or

colposuspension if MUS
unavailable
GA recs 18 + 24
Offer MUS GA recs 18 + 24

Consider peri-urethral
injections for temporary
Stress
Incontinence
Consider urodynamics
Female
Failed initial management

Offer AUS to men with persistent
moderate to severe PPI
GB rec 13
Consider fixed slings for

men with PRPI
GC rec 20
GC rec 20
Consider peri-urethral injection

for temporary relief, and
minimally invasive
compressione devices
Stress
Incontinence
Offer the opportunity

for treatment with SNS
GA rec 22
Urgency
Incontinence
Discuss bladder augmentation or urinary diversion

GC rec 23
Offer Botulinum
toxin A
GA rec 21
Mixed
Incontinence
Rec 24
Re-evaluate, perform urodynamics and cystoscopy, and consider imaging of

lower UT
GB rec 6
Male
Failed initial management
GUIDELINES ON
UROLOGICAL INFECTIONS
M.Grabe (chairman), T.E. Bjerklund-Johansen, H. Botto,

M. ek, K.G. Naber, R.S. Pickard, P. Tenke, F. Wagenlehner,
B. Wullt
Introduction
Infections of the urinary tract (UTIs) pose a serious health
problem for patients at high cost for society. UTIs are also
the most frequent healthcare associated infections.
E. coli is the predominating pathogen in uncomplicated
UTIs while other Enterobacteriaceae and Enterococcus
spp are isolated in higher frequency in patients with
urological diseases. The present state of microbial resistance
development is alarming and the rates of resistance are
related to the amount of antibiotics used in the different
countries. Particularly worrisome is the increasing resistance
to broad spectrum antibiotics. It is thus essential to limit
the use of antibiotics in general and fluoroquinolones and
cephalosporins in particular, especially in uncomplicated
infections and asymptomatic bacteriuria.
Classification and definitions

For practical clinical reasons, urinary tract infections (UTIs)
and male genital tract infections are classified into entities
defined by the predominant clinical symptoms (Table 1).
224 Urological Infections
Table 1: Classification of urinary and male genital tract

infections
Uncomplicated lower UTI (cystitis)
Uncomplicated pyelonephritis
Complicated UTI with or without pyelonephritis
Urosepsis
Urethritis
Prostatitis, epididymitis, orchitis
The definitions of bacteriuria and pyuria are listed in Table 2.
Table 2: Significant bacteriuria in adults

1. > 103 uropathogens/mL of midstream urine in acute
uncomplicated cystitis in female.
2. > 104 uropathogens/mL of midstream urine in acute
uncomplicated pyelonephritis in female.
3. > 105 uropathogens/mL in midstream urine of women or
104 uropathogens/mL of midstream urine in men (or in
straight catheter urine in women) with complicated UTI.
4. In a suprapubic bladder puncture specimen, any count of
bacteria is relevant.
Asymptomatic bacteriuria
Asymptomatic bacteriuria is defined as two positive urine
cultures taken more than 24 hours apart containing 105
uropathogens/mL of the same bacterial strain (usually only
the species can be detected).
Pyuria
The diagnostic requirement for pyuria is 10 white blood cells
per high-power field (HPF) (x400) in the resuspended sediUrological Infections 225
ment of a centrifuged aliquot of urine or per mm3 in unspun

urine. For routine investigation, a dipstick method can also
be used, including a leukocyte esterase test and the assessment of haemoglobin and of nitrites.
Urethritis
Symptomatic urethritis is characterised by alguria and purulent discharge.
Classification of prostatitis/chronic pelvic pain syndrome
(CPPS)
It is recommended that the classification according to
NIDDK/NIH is used (Table 3).
Table 3: Classification of prostatitis according to

NIDDK/NIH
I
II
III
IV
Acute bacterial prostatitis (ABP)

Chronic bacterial prostatitis (CBP)
Chronic pelvic pain syndrome (CPPS)
A. Inflammatory CPPS: WBC in EPS/voided
bladder urine-3 (VB3)/semen
B. Non-inflammatory CPPS: no WBC/EPS/VB3/semen
Asymptomatic inflammatory prostatitis (histological
prostatitis)
Epididymitis, orchitis
Most cases of epididymitis, with or without orchitis, are
caused by common urinary pathogens. Bladder outlet
obstruction and urogenital malformations are risk factors for
this type of infection. Consider Chlamydia trachomatis infection in the younger male population.
Diagnosis
UTI (general)
A disease history, physical examination and dipstick urinalysis, including white and red blood cells and nitrite reaction,
is recommended for routine diagnosis. Except in isolated
episodes of uncomplicated lower UTI (cystitis) in premenopausal, healthy women, a urine culture is recommended in
all other types of UTI before treatment, so allowing antimicrobial therapy to be adjusted if necessary.
Pyelonephritis
In cases of suspected pyelonephritis, it may be necessary to
evaluate the upper urinary tract to rule out upper urinary
tract obstruction or stone disease.
Urethritis
Pyogenic urethritis is indicated by a Gram stain of secretion
or urethral smear that shows more than five leukocytes per
HPF (x1,000) and in case of gonorrhoea gonococci are located intracellularly as Gram-negative diplococci. A positive
leukocyte esterase test or more than 10 leukocytes per HPF
(x400) in the first voiding urine specimen is diagnostic.
Prostatitis/CPPS
In patients with prostatitis-like symptoms, an attempt should
be made to differentiate between bacterial prostatitis and
CPPS. This is best done by the four glass test according to
Mearse & Stamey, if acute UTI and STD can be ruled out.
Urological Infections 227
Table 4: Recommendations for antimicrobial therapy in urology

Diagnosis
Most frequent pathogen/species
Cystitis
E. coli
acute,
Klebsiella
uncomplicated
Proteus

Staphylococci

Pyelonephritis
E. coli
acute,
Proteus
uncomplicated
Klebsiella

Other enterobacteria

Staphylococci
UTI with
E. coli
complicating
Enterococci
factors
Pseudomonas

Staphylococci
Nosocomial UTI
Klebsiella

Proteus
Pyelonephritis
Enterobacter
acute,
complicated
(Candida)

I
w
c
A
ogy
Initial, empirical antimicrobial therapy
TMP-SMX1
Nitrofurantoin
Fosfomycin trometamol
Pivmecillinam
Fluoroquinolone (altern.)2, 3
Fluoroquinolone2
Cephalosporin (group 3a)
Alternatives:
Aminopenicillin/BLI
Aminoglycoside
Fluoroquinolone2
Aminopenicillin/BLI
Cephalosporin (group 2)
Cephalosporin (group 3a)
Aminoglycoside
In case of failure of initial therapy
within 1-3 days or in clinically severe
cases:
Anti-Pseudomonas active:
Fluoroquinolone, if not used initially
Acylaminopenicillin/BLI
Cephalosporin (group 3b)
Carbapenem
Aminoglycoside
In case of Candida:
Fluconazole
Amphotericin B
Therapy duration
3 days
(5-)7 days
1 day
(3-)5 days
(1-)3 days
7-10 days
3-5 days after

defeverescence or
control/elimination
of complicating
factor
Prostatitis
E. coli
acute, chronic

Pseudomonas
Epididymitis
Enterococci
acute
Staphylococci

Chlamydia

Ureaplasma
Urosepsis
E. coli


After urological

interventions - multi-

resistant pathogens:

Pseudomonas

Proteus

Serratia

Enterobacter
1Only in areas with resistance rate < 20% (for E. coli).
2Fluoroquinolone with mainly renal excretion (see text).
3Avoid Fluoroquinolones in uncomplicated cystitis whenever possible.
BLI = beta-lactamase inhibitor; UTI = urinary tract infection.
Treatment and Prophylaxis

Treatment of UTI depends on a variety of factors. Table
4 provides an overview of the most common pathogens,
antimicrobial agents and duration of treatment for different
conditions. Prophylactic treatment may be recommended for
patients with recurrent UTI. The regimens shown in Table
5 have a documented effect in preventing recurrent UTI in
women.
Fluoroquinolone2
Alternative in acute bacterial prostatitis:
Cephalosporin (group 3a/b)
In case of Chlamydia or Ureaplasma:
Doxycycline
Macrolide
Acute:
2-4 weeks
Cephalosporin (group 3a/b)

Fluoroquinolone2
Anti-Pseudomonas active
acylaminopenicillin/BLI
Carbapenem
Aminoglycoside
3-5 days after

defeverescence or
control/elimination
of complicating
factor
Chronic:
4-6 weeks or longer
le.
Special situations
UTI in pregnancy
Asymptomatic bacteriuria is treated with a 7-day course
based on sensitivity testing. For recurrent infections (symptomatic or asymptomatic), either cephalexin, 125-250 mg/day,
or nitrofurantoin, 50 mg/day, may be used for prophylaxis.
UTI in postmenopausal women
In women with recurrent infection, intravaginal oestriol is
recommended. If this is not effective, antibiotic prophylaxis
could be considered.
UTI in children
Treatment periods should be extended to 7-10 days. Tetracyclines and fluoroquinolones should not be used because of
adverse effects on teeth and cartilage.
Acute uncomplicated UTI in young men
Treatment should last at least 7 days.
Complicated UTI due to urological disorders
The underlying disorder must be managed if a permanent
cure is to be achieved. Whenever possible, treatment should
be guided by urine culture to avoid inducing resistant strains.
Sepsis in urology (urosepsis)
Patients with UTI may develop sepsis. Early signs of systemic
inflammatory response (fever or hypothermia, tachycardia,
tachypnoea, hypotension, oliguria, leukopenia) should be
recognized as the first signs of possible multi-organ failure.
As well as appropriate antibiotic therapy, life-support therapy
in collaboration with an intensive care specialist may be necessary. Any obstruction in the urinary tract must be drained.
Table 5: Recommendations for antimicrobial

prophylaxis of recurrent uncomplicated UTI
Agent1
Standard regimen
Nitrofurantoin
Nitrofurantoin macrocrystals
TMP-SMX
Dose
50 mg/day
100 mg/day
40/200 mg/day or
three times weekly
100 mg/day
3 g/10 day
TMP
Fosfomycin trometamol
Breakthrough infections
Ciprofloxacin
125 mg/day
Norfloxacin
200-400 mg/day
Pefloxacin
800 mg/week
During pregnancy
Cephalexin
125 mg/day
Cefaclor
250 mg/day
1Taken at bedtime.
TMP = trimethoprim-sulphamethoxazole.
Follow-up of patients with UTI

For routine follow-up after uncomplicated UTI and
pyelonephritis in women, dipstick urinanalysis is sufficient.
In women with a recurrence of UTI within 2 weeks,
repeated urinary culture with antimicrobial testing and
urinary tract evaluation is recommended.
In the elderly, newly developed recurrent UTI may warrant a full evaluation of the urinary tract.
In men with UTI, an urological evaluation should be
performed in adolescent patients, cases of recurrent infection and all cases of pyelonephritis. This recommendation
should also be followed in patients with prostatitis, epididymitis and orchitis.
In children, investigations are indicated after two episodes
of UTI in girls and one episode in boys. Recommended
investigations are ultrasonography of the urinary tract
supplemented by voiding cystourethrography.
Urethritis
The following guidelines for therapy comply with the recommendations of the Center for Disease Control and Prevention
(2002). For the treatment of gonorrhoea, the following antimicrobials can be recommended:
First choice
Cefixime 400 mg orally
as a single dose
Ceftriaxone 1g im
as a single dose
(im with local anaesthetic)
Second choice
Ciprofloxacin 500 mg orally or
Ofloxacin 400 mg orally or
Levofloxacin 250 mg orally
as a single dose
As gonorrhoea is often accompanied by chlamydial infection, an antichlamydial active therapy should be added.
The following treatment has been successfully applied in
Chlamydia trachomatis infections:
First choice
Azithromycin
1 g (= 4 caps @ 250 mg)
orally as single dose
Doxycycline
2 times daily 100 mg orally
for 7 days

Second choice
Erythromycin
4 times daily 500 mg
orally for 7 days
Ofloxacin 2 times daily
300 mg orally or
Levofloxacin once daily
500 mg orally
for 7 days
If therapy fails, infections with Trichomonas vaginalis and/or

Mycoplasma spp. should be considered. These can be treated
with a combination of metronidazole (2 g orally as a single
dose) and erythromycin (500 mg orally, 4 times daily, for 7
days).
Prostatitis
Acute bacterial prostatitis can be a serious infection. The
parenteral administration of high doses of bactericidal antibiotics, such as an aminoglycoside and a penicillin derivative
or a third-generation cephalosporin, is required until defervescence occurs and infection parameters return to normal.
In less severe cases, a fluoroquinolone may be given orally
for at least 10 days.
In chronic bacterial prostatitis and inflammatory CPPS, a
fluoroquinolone or trimethoprim should be given orally for 2
weeks after the initial diagnosis. The patient should then be
reassessed and antibiotics only continued if the pretreatment
cultures were positive or if the patient has reported positive
effects from the treatment. A total treatment period of 4-6
weeks is recommended.
Table 6:
Recommendations for peri-operative antibacterial
Procedure
Pathogens
Prophylaxis

(expected)
(standard)
Diagnostic procedures
Transrectal biopsy of the Enterobacteriaceae
All patients
prostate
(Anaerobes)

Cystoscopy
Enterobacteriaceae
No
Urodynamic study
Enterococci

Staphylococci
Ureteroscopy
Enterobacteriaceae
No

Enterococci

Staphylococci
Endourological surgery and ESWL
ESWL
Enterobacteriaceae
No

Enterococci

Ureteroscopy for
Enterobacteriaceae
No
uncomplicated distal stone Enterococci

Staphylococci

Ureteroscopy of proximal Enterobacteriaceae
All patients
or impacted stone and
Enterococci
percutaneous stone
Staphylococci
extraction

TUR of the prostate
Enterobacteriaceae All patients

Enterococci

pro
F
T
M
T
C
g
T
C
g
T
C
3
A
T
C
3
A
F
T
C
3
A
F
T
C
3
A
erial
prophylaxis in urology
Antibiotics
Remarks
Fluoroquinolones
TMP SMX
Metronidazole1
TMP SMX
Cephalosporin 2nd
generation
TMP SMX
Cephalosporin 2nd
generation
Single dose effective in low

risk. Consider prolonged
course in risk patients
Consider in risk patients
TMP SMX
Cephalosporin 2nd or
3rd generation
Aminopenicillin/BLI2
TMP SMX
3rd generation
Aminopenicillin/BLI
Fluoroquinolones
TMP SMX
3rd generation
Aminopenicillin/BLI
Fluoroquinolones
TMP SMX
3rd generation
Aminopenicillin/BLI
In patients with stent or

nephrostomy tube or other
risk factor
No studies
Short course,
Length to be determined
Intravenous suggested at
operation
Low-risk patients and
small-size prostate
require no prophylaxis
TUR of bladder tumour

Enterobacteriaceae
No
T

Enterococci
C

3

A
Open or laparoscopic urological surgery3
Clean operations
Skin-related
No

pathogens,

e.g. staphylococci

Catheter-

associated

uropathogens
Clean-contaminated
Enterobacteriaceae
Recommended
T
(opening of urinary tract) Enterococci
C

Staphylococci
3

A
Clean-contaminated/
Enterobacteriaceae
All patients
contaminated (use of bowel Enterococci
segments):
Anaerobes

Skin-related

bacteria
Implant of prosthetic
Skin-related
All patients
devices
bacteria,

e.g. staphylococci

C
3
M
BLI=beta-lactamase inhibitor; TMP SMX = trimethoprim with or

resection.
1No evidence for the use of mettronidazole in prostate core biopsies.
2Gram-negative bacteria excluding Pseudomonas aeruginosa.
3Classifications of surgical field contamination (CDC).
C
3
P
(
TMP SMX
3rd generation
Aminopenicillin/BLI

and large tumours
Consider in high-risk
patients.
Short post-operative
catheter requires no
treatment
ded
TMP SMX
3rd generation
Aminopenicillin/BLI
Single peri-operative
course
3rd generation
Metronidazole
As for colonic surgery
3rd generation
Penicillin
(penicillinase stable)
without sulphamethoxale (co-trimoxazole); TUR = transurethral
Combination therapy with antibiotics and -blockers:

Urodynamic studies have shown increased urethral closing
pressure in patients with chronic prostatitis. Combination
treatment with -blockers and antibiotics has been reported
to have a higher cure rate than antibiotics alone in inflammatory CPPS. This treatment option is favoured by many
urologists.
Surgery: Generally, surgery should be avoided in the treatment of prostatitis, except for the drainage of prostatic
abscesses.
Epididymitis, orchitis
Prior to antimicrobial therapy, a urethral swab and midstream urine sample should be obtained for microbiological
investigation. The first choice of drug therapy should be fluoroquinolones, preferably those agents that react well against
C. trachomatis (e.g. ofloxacin, levofloxacin), because of their
broad antibacterial spectra and favourable penetration into
urogenital tract tissues.
In cases caused by C. trachomatis, treatment may also be continued with doxycycline, 200 mg/day, for a total treatment
period of at least 2 weeks. Macrolides are alternative agents.
In cases of C. trachomatis infection, the sexual partner should
also be treated.
Perioperative antibacterial prophylaxis in urological

surgery
The main aim of antimicrobial prophylaxis in urology is to
prevent symptomatic or febrile genitourinary infections, such
as acute pyelonephritis, prostatitis, epididymitis and urosep240 Urological Infections
sis, as well as serious wound infections. The recommendations for short-term peri-operative antibacterial prophylaxis
in standard urological interventions are listed in table 6.
This short booklet is based on the more comprehensive EAU guidelines (ISBN
Urology at their website, http://www.uroweb.org.
GUIDELINES ON NEUROGENIC LOWER

URINARY TRACT DYSFUNCTION
M. Sthrer (chairman), B. Blok, D. Castro-Diaz, E. ChartierKastler, P. Denys, G. Kramer, J. Pannek, G. del Popolo,
P. Radziszewski, J-J. Wyndaele
Introduction
Before the 1980s, considerable morbidity was associated with
renal failure in patients with neurogenic lower urinary tract
dysfunction (NLUTD). Most patients with NLUTD require
life-long care to maintain their quality of life (QoL) and
maximise life-expectancy. Significant technological developments that have occurred over the last 30 years have helped
to achieve these goals.
Methodology
Where possible, the Panel has used a three-tier system (A-C)
to grade treatment recommendations and thus assist clinicians in determining the validity of a recommendation.
Terminology
The terminology used and the diagnostic procedures outlined follow the recommendations for the investigation of
the lower urinary tract (LUT) published by the International
Continence Society (ICS).
242 Neurogenic Lower Urinary Tract Dysfunction
Risk factors and epidemiology

All central and peripheral neurological disorders carry a high
risk of causing functional disturbances of the urinary tract.
Classification
Several classification systems have been proposed for NLUTD.
The panel recommends a functional classification for motor
function based on urodynamic and clinical findings (Figure 1).
Fig. 1: The EAU-Madersbacher classification system
Detrusor

Over-
active
Overactive
Over-
active
Over-
active
Underactive Normo-active
Urethral sphincter
Underactive
Overactive
Detrusor

Under-
active
Under-
active
Normo-
active
Underactive Normo-active Overactive

Urethral sphincter
Normoactive
Underactive
Adapted from Madersbacher et al.

Neurogenic Lower Urinary Tract Dysfunction 243
Timing of diagnosis and treatment

In both congenital and acquired NLUTD, early diagnosis and
treatment are essential, as irreversible changes within the
LUT may occur, even when the related neuropathological
signs are normal. Also, remember that NLUTD can, by itself,
be the presenting feature of neurological pathology.
Diagnosis
Patient assessment
Diagnosis of NLUTD should be based on a comprehensive
assessment of neurological and non-neurological conditions.
Initial assessment should include a detailed history, physical
examination, and urinalysis.
History
An extensive general and specific history is mandatory and
should concentrate on past and present symptoms and disorders of the urinary tract, bowel, and sexual and neurological
function. Special attention should be paid to possible warning signs and symptoms (e.g. pain, infection, haematuria,
fever) that warrant further investigation.
The neurological status should be described as completely
as possible. All sensations and reflexes in the urogenital area
must be tested, including detailed testing of the anal sphincter and pelvic floor functions (Figure 2). Availability of this
clinical information is essential for the reliable interpretation
of subsequent diagnostic investigations.
Fig. 2: The neurological status of a patient with NLUTD

must be described as completely as possible (a - dermatomes, b - associated reflexes)

Fig. 2a - Dermatomes of spinal cord levels L2-S4.
Fig. 2b - Urogenital and other reflexes in lower spinal cord.

Urodynamic tests
A bladder diary should be recorded for at least 2-3 days.
Uroflowmetry and ultrasound assessment of post-void residual should be repeated at least 2 or 3 times in patients able
to void.
Invasive urodynamic studies comprise mandatory assessment
tools to determine the exact type of NLUTD (Table 1).
Table 1: Guidelines for urodynamics and

uro-neurophysiology tests in NLUTD
Urodynamic investigation is necessary to document
the (dys-)function of the LUT.
The recording of a bladder diary is advisable.
Non-invasive testing is mandatory before invasive urodynamics is planned.
Video-urodynamics is currently the preferred method
for invasive urodynamics in patients with NLUTD. If
this is not available, then a filling cystometry continuing into a pressure flow study should be performed.
For standard urodynamic testing, a physiological filling rate (see Table 1, e.g. not faster than 20 mL/min)
and body-warm fluid must be used.
Specific uro-neurophysiological tests and provocative
manoeuvres (e.g. fast filling cystometry with cooled
saline [the ice water test], coughing, tapping, anal
stretch) are elective procedures.
GR
A
B
A
A
Filling cystometry is the only procedure that quantifies the

filling function of the bladder. However, when filling cystometry is used alone, the results have limited significance.
Measurement of detrusor leak point pressure (DLPP) has limited diagnostic value; it is not recommended as a stand alone
test.
Pressure flow studies: the function of the LUT must also be
recorded during the voiding phase.
Video-urodynamics combines filling cystometry and pressure
flow studies with radiological imaging. Currently, video-urodynamics is considered to provide the most comprehensive
information evaluating NLUTD.
Electromyography (EMG) is a semi-quantitative measure of
pelvic floor activity, which can be used to detect detrusor/
sphincter dyssynergia (DSD) and pelvic floor relaxation disorders.
Table 2: Characteristic findings in NLUTD*

Filling phase
Increased, decreased, or absent bladder sensation
Vegetative non-specific sensations
Low bladder compliance
High capacity bladder
Detrusor overactivity, spontaneous or provoked
Incompetent urethral closure mechanism
Voiding phase
Acontractile or underactive detrusor
Bladder outlet obstruction

DSD
Non-relaxing urethral sphincter obstruction
These signs warrant further neurological evaluation, as
LUTD may be the presenting symptom of a neurological
disease.
*modified from ICS publication.
Treatment
Introduction
Treatment of NLUTD aims to protect the upper urinary tract,
and improve continence, QoL and, whenever possible, LUT
function.
In patients with a high detrusor pressure in the filling phase,
the principal aim of treatment is conversion of an overactive,
high-pressure bladder into a low-pressure reservoir; even if
this should result in a high post-void residual. The patients
QoL is a prime consideration when making any treatment
decision.
Drug treatment for neurogenic detrusor overactivity (NDO)
Antimuscarinic agents are currently the most widely used
treatment, although most of the available drugs have not
been registered for the treatment of this patient population.
Antimuscarinic agents can also be given intravesically.
Drug treatment for neurogenic detrusor underactivity
There is no evidence of effective drug treatment for detrusor
underactivity.
Drug treatment to decrease bladder outlet resistance

Selective and non-selective alpha-blockers have been partially
successful in decreasing bladder outlet resistance, residual
urine and autonomic dysreflexia.
Catheterisation
Intermittent, self- or third-party, catheterisation (IC) is the
gold standard for the management of NLUTD. Compared to
clean IC, aseptic IC provides significant benefit in reducing
the potential for contamination.
On average, IC, using a 12-14 Fr catheter, is needed 4-6
times per day.
Indwelling transurethral IC and, to a lesser extent, suprapubic cystostomy should be avoided as they are risk factors for
UTI and significant long-term complications. If indwelling
catheters must be used, empirical evidence and expert opinion suggests silicone catheters provide advantages over latex
catheters.
Assisted bladder emptying
Triggered reflex voiding is not recommended as there is a
risk of pathologically elevated bladder pressures. Only in the
case of absence, or surgically reduced, outlet obstruction it
may be an option.
Bladder compression techniques to expel urine (Crede) and
voiding by abdominal straining (Valsalva manoeuvre) create
high pressures and are potentially hazardous, and their use
should be discouraged.
Rehabilitation
In selected patients, pelvic floor muscle exercises, pelvic floor
electro-stimulation, and biofeedback might be beneficial.
External appliances
Social continence for the incontinent patient can be achieved
using an appropriate method of urine collection.
Minimally invasive treatment

Botulinum toxin A injections in the bladder
Botulinum toxin A causes a long-lasting (approximately
9 months), reversible, chemical denervation.
Intravesical vanilloid treatment
Resiniferatoxin and capsaicin have limited clinical efficacy
compared to botulinum toxin A injected in the detrusor.
Bladder neck and urethral procedures
Reduction of the bladder outlet resistance, to protect the
upper urinary tract, can be achieved by sphincterotomy or
chemical denervation of the sphincter using botulinum toxin
A. Insertion of urethral stents is not recommended.
Increasing bladder outlet resistance using bulking agents or
urethral inserts, or alternative appliances is not recommended for long-term treatment.
NDO and reflux

Vesico-ureteral reflux should be managed by lowering intravesical pressure. If reflux is persistent, intervention using
bulking agents or ureteral re-implantation can be considered.
Surgical treatment
Overactive detrusor
Bladder augmentation/clam cystoplasty is indicated for an
overactive detrusor, when less invasive procedures have
failed. Alternative options include: auto-augmentation (myomectomy), dorsal rhizotomy, with or without sacral anterior
root stimulation (SARS) (complete lesions), and neuromodulation (incomplete lesions). Substitution, with either
continent or incontinent diversion, is indicated for the small
contracted non-compliant bladder.
Fig. 3: Surgery for neurogenic detrusor overactivity
Surgery for neurogenic detrusor overactivity
All lesions
Incomplete lesion
Complete lesion
Botulinum Toxin A
Neuromodulation
Deafferentation
Auto-Augmentation (optional)
Neurostimulation
Clam Cystoplasty
Enterocystoplasty
Underactive detrusor
Sacral anterior root stimulation (complete lesions) and sacral neuromodulation (incomplete lesions) are effective in
selected patients.
Sphincter insufficiency (underactive urethra)
The artificial urinary sphincter is the preferred tried and
tested treatment.
Procedures to treat sphincter incompetence are suitable only

when the detrusor activity is, or can be, controlled and there
is no significant associated vesico-ureteral reflux.
Quality of life
QoL represents a very important aspect in the global management of the patient who has NLUTD. Restoration and maintenance of the patients QoL it as much as possible, should be
one of the major aims of treatment. QoL should be integral
to the evaluation of lower urinary tract symptoms in patients
with NLUTD and also, when considering any type of treatment for neurogenic bladder dysfunction.
Follow-up
Meticulous follow-up and regular checks are essential.
Individualised patient follow-up is imperative to safeguard
QoL and life expectancy. The underlying pathology and the
state of the urinary tract dictate the frequency of follow-up
required.
Table 3: Minimum follow-up required in patients with

NLUTD*
Investigation
Urinalysis
Ultrasound of the upper
urinary tract, bladder status,
post void residual
Physical examination, blood
biochemistry, and urine
microbiology
Frequency
At least once every 6
months
Every 6 months
GR
A
Annually
A
(Video-) urodynamic inves- Every 2 years
tigations in patients without
detrusor overactivity and
with normal bladder compliance
A
(Video-) urodynamic inves- At least once a year
tigations in patients with
detrusor overactivity, and/or
low bladder compliance
The need for detailed special investigations must be determined on the basis of the patients risk profile (see above),
but should, where indicated, include a video-urodynamic
study, which should be carried out in an institution with
neuro-urological expertise.
*Grades of recommendation assigned on basis of panel consensus.
Summary
NLUTD is a multi-faceted pathology. Extensive investigation and a precise diagnosis are required before the clinician
can initiate individualised therapy. Treatment must take into
account the patients medical and physical condition and
expectations with regard to his/her future social, physical,
and medical situation.
GUIDELINES ON
UROLOGICAL TRAUMA
N. Djakovic, Th. Lynch, L. Martnez-Pieiro, Y. Mor, E. Plas,

E. Serafetinides, L. Turkeri, R.A. Santucci, M. Hohenfellner

Renal Trauma
Eur Urol 2005;47(1):1-15
Background
Renal injuries account for 1-5% of all traumas.
Table 1: Injury severity scale for the kidney*#

Grade Description
Contusion or non-expanding subcapsular haemato1
ma, no laceration
Non-expanding perirenal haematoma, cortical lac2
eration < 1 cm deep without extravasation
Cortical laceration > 1 cm without urinary
3
extravasation
Laceration: through corticomedullary junction
4
into collecting system or vascular: segmental renal
artery or vein injury with contained haematoma
5
Laceration: shattered kidney or vascular: renal
pedicle injury or avulsion
* Adapted from the American Association for the Surgery of
Trauma (AAST).
# Advance one grade for multiple injuries up to grade 3.
254 Urological Trauma
Diagnosis
History: time and setting of incident, past renal surgery,
known renal abnormalities.
Exam: for non-genitourinary injuries:
Lab: gross hematuria, dipstick urine analysis, serial
haematocrit, baseline serum creatinine.
Patient selection: blunt trauma with macroscopic or
microscopic haematuria and hypotension, a history of
rapid deceleration injury and/or significant associated
injuries should undergo radiographic evaluation. Any
degree of haematuria after penetrating abdominal or
thoracic injury requires urgent imaging.
Imaging: computed tomography (CT) scan with
and without intravenous contrast material in
haemodynamically stable patients. Patients requiring
exploration should undergo an intraoperative one-shot
intravenous pyelography (IVP) with bolus intravenous
injection of 2 mL/kg contrast. Ultrasonography may be
helpful during the primary evaluation or follow-up of
recuperating patients. Formal IVP, magnetic resonance
imaging (MRI) and radiographic scintigraphy are secondline methods of imaging. Angiography can be used for
diagnosis and simultaneous selective embolisation of
bleeding vessels if necessary.
Treatment
Indications for surgical management include haemodynamic
instability, expanding or pulsatile perirenal haematoma, and
main renal artery avulsion or thrombosis in a single kidney
(Figures 1 and 2).
Urological Trauma 255
Figure 1: Evaluation of blunt renal trauma in adults

Suspected adult blunt
renal trauma*
Determine haemodynamic stability
Stable
Gross haematuria
Renal imaging**
Grade 3-4
Rapid
deceleration
injury or
major associated
injuries
Grade 1-2
Unstable
Microscopic haematuria
Observation
Stable
Observation
Bed rest,
Serial Ht,
Antibiotics
Normal IVP
Retroperitoneal haematoma
Pulsatile or expanding
Grade 5
Associated injuries requiring
laparotomy
Emergency
laparotomy
One-shot IVP
Renal exploration***
Abnormal IVP
* Suspected renal trauma results from reported mechanism of injury and

** Renal imaging: CT scans are the gold standard for evaluating blunt and
penetrating renal injuries in stable patients. In settings where the method
is not available, the urologist should rely on other imaging modalities
(IVP, angiography, radiographic scintigraphy, MRI).
*** Renal exploration: although renal salvage is a primary goal for the urologist, decisions concerning the viability of the organ and the type of reconstruction are made during the operation.
Post-operative care, follow-up, and complications

The role of repeat imaging is unknown. Some experts recommend repeat imaging within 2-4 days of injury. Nuclear
scintigraphy may be useful for documenting functional
recovery. Patient follow-up: physical examination, urinalysis,
individualised radiological investigation, serial blood pressure
Figure 2: Evaluation of penetrating renal trauma in adults

Suspected adult penetrating
renal trauma*
Determine haemodynamic stability
Stable
Unstable
Emergency
laparotomy
One-shot IVP
Renal imaging**
Grade 3
Grade 5
Grade 1-2
Observation
Stable
Observation
Bed rest,
Serial Ht,
Antibiotics
Associated
injuries
requiring
laparotomy
Normal IVP
Retroperitoneal haematoma
Pulsatile or expanding
Renal exploration***
Abnormal IVP
* Suspected renal trauma results from reported mechanism of injury and

** Renal imaging: CT scans are the gold standard for evaluating blunt and
penetrating renal injuries in stable patients. In settings where the method
is not available, the urologist should rely on other imaging modalities
(IVP, angiography, radiographic scintigraphy, MRI).
*** Renal exploration: although renal salvage is a primary goal for the urologist, decisions concerning the viability of the organ and the type of reconstruction are made during the operation.
measurement, and serum determination of renal function.

Long-term follow-up should include monitoring for renovascular hypertension.
Complications (bleeding, infection, perinephric abscess, sepsis, urinary fistula, hypertension, urinary extravasation, urinoma, hydronephrosis, calculus formation, chronic pyeloneUrological Trauma 257
phritis, arteriovenous fistula, and pseudoaneurysms) require

a thorough radiographic evaluation. Medical management
and minimally invasive techniques should be the first choice,
while renal salvage should be attempted when exploration is
necessary. Nephrectomy may be required.
Ureteral Trauma
Background
External trauma to the ureter is rare. Seventy-five percent
of ureteral injuries are iatrogenic, 18% from blunt trauma,
and 7% from penetrating trauma. The most common site of
injury is the lower third (74%).
Table 2: Injury severity scale for the ureter*

Grade
1
2
3
4
5
Description
Haematoma only
Laceration < 50% of circumference
Laceration > 50% of circumference
Complete tear < 2 cm of devascularisation
Complete tear > 2 cm of devascularisation
* Adapted from the AAST.
Diagnosis
The sine qua non is extravasation of radiological contrast
material. The diagnosis is most often made with intraoperative one-shot IVP and CT. If the CT scan is non-diagnostic,
then do IVP or retrograde pyelography.
Treatment
Minimal injury can be managed with ureteral stenting or by
placement of a nephrostomy tube. Ureteral injury complicat258 Urological Trauma
ing vascular graft procedures are controversial: best evidence

is to save the kidney by judicious ureteral repair but older
citations suggest immediate nephrectomy.
In complete injuries the type of reconstructive repair procedure depends on the nature and site of the injury. The
options are:
1. Upper third: uretero-ureterostomy.
2. Middle third: uretero-ureterostomy or Boari flap and reimplantation (staged, do not do acutely).
3. Lower third: direct reimplantation or psoas hitch or
Blandy cystoplasty.
4. Complete ureteral loss: ileal interposition (delayed) or
autotransplantation (delayed). Damage control first: tie off
ureter, place percutaneous nephrostomy.
Bladder Trauma
Background
Blunt trauma accounts for 67-86% of bladder ruptures, is primarily caused by motor vehicle accidents, and may be classified as extraperitoneal or intraperitoneal.
Table 3: Injury severity scale for the bladder*

Grade Description
Haematoma
1
Laceration
Laceration
2
3
Laceration
- Contusion, intramural haematoma

- Partial thickness
- Extraperitoneal bladder wall
laceration < 2 cm
- Extraperitoneal (> 2 cm) or intraperi-toneal (< 2 cm) bladder wall
laceration
Laceration
Laceration
- Intraperitoneal bladder wall laceration > 2 cm

- Intraperitoneal or extraperitoneal
bladder wall laceration extending
into the bladder neck or ureteral
orifice (trigone)
Diagnosis
The most common signs and symptoms are:
Gross haematuria, abdominal tenderness, inability to void,
suprapubic bruising, and abdominal distension.
Extravasation of urine may result in swelling in the perineum, scrotum and/or anterior abdominal wall.
The combination of pelvic fracture and gross haematuria
constitutes an indication for cystography. In patients with
pelvic fracture and microhaematuria, imaging should be
reserved for those with anterior rami fractures (straddle
fracture) or Malgaigne type severe ring disruption (Figure
3).
Retrograde cystography is the standard diagnostic procedure. The bladder must be distended by the instillation of
350 mL of contrast media. A post-drainage film must be
obtained. CT cystography is an excellent alternative.
Routine cystoscopy is recommended after major gynecological operations and/or incontinence surgery.
Treatment
Extraperitoneal ruptures can be managed by catheter
drainage only.
Bladder neck involvement, the presence of bone fragments
in the bladder wall, or entrapment of the bladder wall

necessitates open repair.
Intraperitoneal ruptures are managed by surgical repair.
Urethral Trauma
Background
Injuries to the posterior urethra (PU) occur with pelvic fractures, mostly as a result of motor vehicle accidents. The male
PU is injured in 4-19% of pelvic fractures, and the female
urethra in 0-6% of all pelvic fractures. The combination of
straddle fractures with diastasis of the sacroiliac joint has
the highest risk of urethral injury. Injuries can vary from
simple stretching to partial rupture to complete disruptions.
Urethral injuries in women are rare. For children, urethral
injuries tend to follow the same mechanism of injury as in
adults, although injuries to the prostate and bladder neck
may be more common.
Injuries to the anterior urethra (AU) are caused by intercourse (penile fracture), penetrating trauma, and placement
of penile constriction bands.
Table 4: Injury severity scale for the urethra*

Grade Description
Contusion - Blood at the urethral meatus; normal
1
urethrogram
Stretch
- Elongation of the urethra without
2
injury
extravasation on urethrography
Partial
- Extravasation of contrast at injury
3
disruption site with contrast visualised in the
bladder
Complete - Extravasation of contrast at injury

disruption site without visualisation in the
bladder; < 2 cm of urethral separation
Complete - Complete transection with > 2 cm
5
disruption urethral separation, or extension into
* Adapted from the AAST. the prostate or vagina
4
Diagnosis
In the absence of blood at the meatus or penile haematoma, urethral injury is less common. Exclude by
catheterisation. Blood at the meatus is present in 37-93%
of patients with PU injury, and in at least 75% of patients
with AU injury. A high-riding prostate is an unreliable
finding. Avoid urethral instrumentation until the urethra
is imaged. In an unstable patient, alternatively, an attempt
can be made to pass a urethral catheter, but if there is any
difficulty a suprapubic catheter is inserted and a retrograde urethrogram performed later.
Blood at the vaginal introitus is present in more than 80%
of female patients with pelvic fractures and co-existing
urethral injuries.
Although non-specific, haematuria on a first voided specimen may indicate urethral injury. The amount of urethral
bleeding correlates poorly with the severity of injury. Pain
on urination or inability to void suggests urethral disruption.
Retrograde urethrography is the gold standard for evaluating urethral injury.
If delayed primary repair is contemplated, and when the
proximal urethra in a simultaneous cystogram and urethrogram is not visualised, either MRI of the PU or endos262 Urological Trauma
copy through the suprapubic tract can be used to define

the anatomy of the PU. In females, urethroscopy may be
an important adjunct for the identification and staging of
urethral injuries.
Treatment
While intervention should be guided by the clinical circumstances, the following algorithms are suggested for the treatment of urethral injuries in males and females (Figures 3-5).
Iatrogenic urethral trauma
The most common form of iatrogenic urethral trauma is that
caused by instruments. Most of the relevant urethral lesions
caused by iatrogenic trauma are strictures. These strictures
are of variable location and severity. They often require different management strategies.
Symptoms of iatrogenic urethral injury
The symptoms of urethral injury caused by improper catheterisation or use of instruments are:
penile and/or perineal pain (100%)
urethral bleeding (86%).
Figure 3: Management of posterior urethral injuries in men

Suspected Urethral Injury
Retrograde Urethrogram
Normal
Prostatomembranous Disruption
Complete Rupture
Penetrating
Treat with suprapubic or

transurethral catheter
Partial Rupture
Blunt
Blunt
Primary open repair.

If patient unstable or
important associated
nonurological
injuries, suprapubic
cystostomy
Urethral contusion
Assess for Acute Surgical Indications:

Bladder neck injury, rectal tear, pie-inthe-sky bladder
Penetrating
Primary open repair.

If patient unstable or
important associated
nonurological
injuries, suprapubic
cystostomy
Suprapubic
Cystostomy
No
Yes
Suprapubic
Cystostomy
Suprapubic Tube +
Endoscopic realignment.
Open if rectal or bladder
injury.
Stricture
or
No stricture
Urethrotomy
Stricture
Option:
Endoscopic realignment if patient
is stable (< day 14)
or
Delayed urethroplasty
Stricture
Stricture
No stricture
if stricture is short (< 1cm)

and flimsy
if stricture is long or denser
Delayed endoscopic optical incision
Salvage urethroplasty
in referal centre
Follow-up
Recommendations for treatment: algorithms (Figures 4-6)

Figure 4: Flow diagram of treatment for iatrogenic urethral
injury caused by improper insertion of a catheter
Suspected iatrogenic urethral injury
(improper catheter insertion)
Urethroscopy
False passage
Pre-existing stenosis
Endoscopic guide wire placement and

catheter insertion
Suprapubic drainage
Stricture
No stricture
Follow-up
If stricture is
longer or denser
If stricture is short
and flimsy
Endoscopic optical
incision
If failure
Urethral
reconstruction
Figure 5: Flow diagram of treatment for stricture after radical prostatectomy

Iatrogenic urethral stricture
Anastomotic stricture after radical
prostatectomy
Dilatation
Endoscopic optical bladder

neck incision
Endoscopic bladder
neck incision
If failure
Open surgery
(reanastomosis)
Urinary diversion
Figure 6: Flow diagram for treatment for stricture after

major abdominal surgery or radiotherapy
Urethral injury due to major
abdominal surgery or radiotherapy
Urinary drainage
Urinary diversion
Major reconstruction
Figure 7: Management of anterior urethral injuries in men

Suspected urethral injury
Retrograde urethrogram
Extravasation
No extravasation
Complete disruption
Partial disruption
Penetrating
Blunt
Urethral contusion
Penetrating
If associated with
penile rupture
Primary urethral
repair
Primary urethral
repair
Suprapubic cystostomy
Stricture
If stricture is
short (< 1 cm) and flimsy
Endoscopic optical incision
Suprapubic cystostomy or
transurethral Foley
catheter
No stricture
If stricture is long or denser
If failure
Formal urethral reconstruction
Follow-up
Figure 8: Management of urethral injuries in women

Haematuria or
blood at the vaginal introitus or
labial swelling
Suspect urethral injury
Urethroscopy
Injured bladder neck or urethra
Patient unstable
No lesions of bladder-urethra
Patient stable
Evaluation of upper
urinary tract
Suprapubic cystostomy
Delayed primary reconstruction
Injury of bladder neck

or proximal urethra
Injury of distal urethra
Retropubic repair of
urethra, bladder and
pelvic floor
Transvaginal repair
of urethra and
pelvic floor
Complications
The risk of impotence caused by delayed urethroplasty is
about 5% and the rate of incontinence is about 4%.
Genital Trauma
Background
A direct blow to the erect penis may cause penile fracture.
Blunt trauma to the scrotum can cause testicular dislocation,
testicular rupture and/or subcutaneous scrotal haematoma.

Traumatic dislocation of the testicle occurs mostly in victims
of car or motorcycle accidents, or in pedestrians run over by
a vehicle. Testicular rupture is found in approximately 50%
of direct blunt traumas to the scrotum.
In females, blunt trauma to the vulva is rare. Penetrating
trauma to the external genitalia is frequently associated with
injuries to other organs.
Diagnosis
Information about the accident should include: involved
persons, animals, vehicles, and weapons. Trauma to external genitalia may be due to abusive assault. In suspicious
cases, a sexual assault forensic exam is necessary (photodocumentation).
Presence or macro- and or microhaematuria requires a
retrograde urethrogram; in females cystoscopy is recommended.
In women with genital injuries and blood at the vaginal
introitus, gynaecologic investigation is indicated.
Patients with penile fracture report a sudden cracking or
popping sound associated with local pain and immediate
detumescence.
Table 5: Injury severity scale for the penis*

Grade Description
Cutaneous laceration/contusion
1
Bucks fascia (cavernosum) laceration without
2
tissue loss
Cutaneous avulsion/laceration through
3
glans/meatus/cavernosal or urethral defect < 2 cm
Cavernosal or urethral defect > 2 cm/partial
4
penectomy
Total penectomy
5
Table 6: Injury severity scale for the scrotum*

Grade Description
Contusion
1
Laceration < 25% of scrotal diameter
2
Laceration > 25% of scrotal diameter
3
Avulsion < 50%
4
Avulsion > 50%
5
Table 7: Injury severity scale for the testis*#

Grade
1
2
3
4
Description
Contusion or haematoma
Subclinical laceration of tunica albuginea
Laceration of tunica albuginea with < 50%
parenchymal loss
Major laceration of tunica albuginea with > 50%
parenchymal loss
Total testicular destruction or avulsion

5
# Advance one grade for bilateral lesions up to grade 5.
Table 8: Injury severity scale for the vulva*#

Grade
1
2
3
4
5
Description
Laceration, superficial (skin only)
Laceration, deep into fat, or muscle
Avulsion; skin, fat or muscle
Injury into adjacent organs (anus, rectum, urethra,
bladder)
Table 9: Injury severity scale for the vagina*#

Grade
1
2
3
4
5
Description
Laceration, superficial (mucosa only)
Laceration, deep into fat or muscle
Laceration, complex, into cervix or peritoneum
Injury into adjacent organs (anus, rectum, urethra,
bladder)
Treatment
Penile trauma
Subcutaneous haematoma, without rupture of the cavernosal tunica albuginea and no immediate detumescence of
the erect penis can be managed with non-steroidal analgesics and ice-packs.
Penile fracture: immediate surgical intervention with closure of the tunica albuginea.
Penetrating penile trauma: surgical exploration and conservative debridement of necrotic tissue is recommended
with primary closure in most cases.
Scrotal trauma
Blunt trauma with subcutaneous haematoma: conservative
management.
Large haematocele or testicular rupture: surgical exploration with excision of necrotic tubules and closure of the
tunica albuginea.
Traumatic dislocation of the testis: can be manually
replaced but secondary orchidopexy is recommended.
(If manual reposition cannot be performed, in situ
orchidopexy is indicated).
Extended laceration of scrotal skin: surgical closure.
Penetrating injuries to the scrotum: surgical exploration
with conservative debridement of non-viable tissue.
Extensive destruction of the tunica albuginea: tunica vaginalis flap can be mobilised for testicular closure.
Complete disruption of the spermatic cord: realignment
without vaso-vasostomy.
Female genital trauma (see Figure 9)
Blunt trauma to the vulva commonly presents as haematomas: non-steroidal antirheumatics and cold packs relieve
pain.
Extended vulvar haematoma or haemodynamically unstable patients: surgical intervention may be indicated.
Vulvar laceration: repair after conservative debridement.
Vaginal lesion: abdominal CT scan for exclusion of additional injuries.
Mass casualty events, triage, and damage control

Definition
A mass casualty event is one in which the number of injured
people is significantly higher than the number of healthcare
providers available.
Causes of mass casualty events
Potential mass casualty events include:
the collapse of buildings or bridges;
earthquakes;
floods;
tsunamis;
train collisions;
aircraft catastrophes;
civilian terrorism.
Triage divides patients into four groups:
1. Patients with life-threatening injuries that require immediate intervention, presenting with Airway compromise,
Breathing failure and/or Circulatory compromise from
ongoing external haemorrhage.
2. Patients with severe but non-life-threatening injuries, in
whom treatment can be acceptably delayed: major fractures, vascular injuries of the limbs and large soft tissue
wounds.
3. Walking wounded with minimal injuries.
4. Patients who are so severely injured that treatment would
require allocation of resources and time that would deny
other, more salvageable patients, timely care. These

patients are given minimal or no treatment, and reevaluated when resources become available. There is no
absolute definition for this group because triage is individualised according to the number and severity of casualties
related to the available resources.
Principles urological consultations during a mass casualty
scenario:
Rule out under-triage by the surgeon in charge, and perform a rapid primary survey of every patient.
Avoid unnecessary imaging procedures such as CT scans
and retrograde urethrography. These procedures are performed later, after mass casualty protocols have been suspended.
Treat unstable patients who are to have surgery using
damage control principles.
Stable patients with suspected renal injuries should
be transferred to the surgical ward without imaging
procedures. Re-evaluate if there is any change in their
haemodynamic status, or when possible as dictated by the
constraints of the mass casualty event. Patients managed
in this delayed fashion should be treated according to traditional trauma management protocols.
Minimal acceptable procedures should be performed
in order to transfer patients to the surgical wards, e.g.
suprapubic drainage of the bladder when bladder or
urethral injuries are suspected, clamping and ligation of
bleeding vessels from wounds to the external genitalia,
etc.

Minor
Conservative
Asssociated injuries
Surgery (laparotomy, etc.)
Primary closure
Conservative
No vaginal injury
Abdominal CT + bloodtransfusion drainage

Conservative
Surgery
Abdominal CT + cystography
Vaginal inspection
Blood at vulvar introitus
Unstable haematocrit
Blood analysis
catheter
Major
Penetrating
History
Urine analysis
Blood analysis
Stable haematocrit
Labial haematoma
Cystoscopy
Vaginal inspection
No associated injuries
Abdominal CT
Vaginal injury
Haematuria
History
Urine analysis
Blood analysis
Blunt
consider sperm swab if indicated
Female genitourinary trauma
Blood at vulvar introitus
Figure 9: Female genitourinary trauma
Conservative
Haematoma
Surgery
Penile fracture
Sonography, possibly MRI
Penis
Blunt
Sonography
possibly scrotal MRI
Sonography
possibly scrotal MRI
Conservative
Surgery (drainage)
Surgery
Rupture
Testis
Contusion
History
Urine analysis
Examination
Male genitourinary trauma - 1
A minor intratesticular haematoma A major intratesticular haematoma
Figure 10: Male genitourinary trama 1
Conservative
surgical repositioning
Sonography
possibly abdominal CT
Dislocation
Urethral trauma evaluation
Haematuria
Figure 11: Male genitourinary trauma 2
Male genito
E
Vaccination (i.e.
Patient stable
Abdominal CT
No associated injuries
Conservative debridement
Primary closure
Urethrography
Associated injuries
Bladder drainage
Debridement and reconstruction of
genitourinary and associated injuries
No extravasation
Transurethral catheter
See guidel
eter
Male genitourinary trauma - 2
History
Urinalysis
Examination
Vaccination (i.e. tetanus, rabies) if indicated
Penetrating
Patient unstable
Urethrography
Stabilize
Extravasation
See guidelines for urethral trauma
CT scan
Not stabilisable
Immediate surgery
Reconstruction if necessary
Associated injuries
Bladder drainage
Debridement and reconstruction of
genitourinary and associated injuries
This short booklet is based on the more comprehensive EAU guidelines

GUIDELINES ON PAIN MANAGEMENT

IN UROLOGY
P. Bader (chair), D. Echtle, V. Fonteyne, K. Livadas, G. De

Meerleer, A. Paez Borda, E.G. Papaioannou, J.H. Vranken
General principles of cancer pain management

The therapeutic strategy depends on the four goals of care:
1. Prolonging survival
2. Optimising comfort
3. Optimising function
4. Relieving pain.
Table 1: Hierarchy of general principles of cancer pain

management
1.
2.
Individualised treatment for each patient.

Causal therapy to be preferred over symptomatic
therapy.
3. Local therapy to be preferred over systemic therapy.
4. Systemic therapy with increasing invasiveness: World
Health Organization (WHO) ladder.
5. Compliance with palliative guidelines.
6. Both psychological counselling and physical therapy
from the very beginning.
Systemic analgesic pharmacotherapy: the analgesic ladder
Analgesic pharmacotherapy is the mainstay of cancer pain
management. Although concurrent use of other interventions
is valuable in many patients, and essential in some, analgesic
278 Pain Management in Urology
drugs are needed in almost every case.

Analgesic drugs can be separated into three groups:
non-opioid analgesics;
opioid analgesics;
adjuvant analgesics.
Adjuvant analgesics are drugs with other primary indications
that can be effective analgesics in specific circumstances.
There are three groups:
corticosteroids;
neuroleptics;
benzodiazepines.
The WHO has proposed a useful approach to drug selection for cancer pain, known as the analgesic ladder. When
combined with appropriate dosing guidelines, this approach
is capable of providing adequate relief to 70-90% of patients
(Figure 1) (LE: 1a).
Figure 1: The World Health Organizations analgesic ladder
Step 3
Non-opioid analgesics
+ strong opioids
+ adjuvant analgesics
Step 2
+ weak opioids
Step 1
Pain Management in Urology 279
Table 2: Treatment of neuropathic pain

Drug
Dosage
Amitriptyline
(nortiptyline)
Gabapentin
Pregabalin
Tramadol
25-75 mg
Frequency
(maximum)
Once per day
600-1200 mg
75-300 mg
50-100 mg
Three times daily

Twice daily
Four times daily
Recommendations
GR
Amitriptyline and nortriptyline are first-line treatment A
for neuropathic pain; nortriptyline has fewer sideeffects.
Tricyclic antidepressants (TCA) must be used cauA
tiously in patients with a history of cardiovascular
disorders, glaucoma, and urine retention.
Gabapentin and pregabalin are first-line treatments
A
for neuropathic pain, especially if TCAs are contraindicated.
GR = grade of recommendation.
Pain management in urological cancers

Table 3: Docetaxel-based chemotherapy versus
mitoxantrone-based regimens in prostate
cancer
Chemotherapy
agent
Plus
additional
therapy
Docetaxel
Prednisone
Frequency Response rate

Pain
QoL
(%)
(%)
Every 3
35
22
weeks
Docetaxel
Mitoxantrone
Prednisone
Prednisone
Weekly
Every 3
weeks
31
22
23
13
Recommendation: Anticancer treatment
LE GR
Hormonal therapy (orchiectomy, LHRH ana1a A
logues, diethylstilboestrol equivalent)
Total androgen blockade: flare prevention, sec2b B
ond line
Intermittent androgen suppression: experimental 3
B
Monotherapy with anti-androgen: currently not 1b A
recommended
First-line treatment controls disease for 12-18
1b A
months; second line individualised
Supportive care
Low-dose glucocorticoids
1b A
Chemotherapy
Mitoxantrone plus prednisolone
1b B
Estramustine + vinblastine or etoposide or pacli- 2b B
taxel
Docetaxel
1b A
Abiratereone
1b A
Cabazitaxel
1b A
Pain management
Pain assessment (localisation, type, severity,
B
overall distress)
Pain due to painful and stable bone metastases (single lesions)
External beam irradiation
1b A
Pain due to painful bony metastases (widespread)
Primary hormonal therapy
1a A
Radioisotopes (strontium-89 or samarium-153)

Bisphosphonates
Systemic pain management
World Health Organization analgesic ladder step
1: NSAID or paracetamol
Opioid administration
Dose titration
Access to breakthrough analgesia
Tricyclic antidepressant and/or anticonvulsant in
case of neuropathic pain
NSAID = non-steroidal anti-inflammatory drug.
2
1b
B
A
1a
2
1b
1a
B
A
A
External beam radiation

Single-fraction radiotherapy is an excellent palliative
treatment for symptomatic bone metastases, resulting in
complete or partial pain relief in 20-50% and in 50-80% of
patients, respectively.
Metastatic epidural spinal cord compression is a severe
complication requiring urgent treatment. Direct decompressive surgery is superior to radiotherapy alone. Primary
radiotherapy is recommended for patients who are not
suited for surgery.
For impending pathological fractures, a prophylactic
orthopaedic procedure should be considered.
Table 4: Criteria for selecting patients for primary

therapy for spinal cord compression
Absolute criteria
Operability
Duration of paraplegia
Life expectancy
Radiosensitivity
Relative criteria
Diagnosis of primary tumour
Bone fragments
with compression
Number of foci of
compression
Surgery
Radiotherapy
Medically operable Medically inoperable
> 48 hours
< 48 hours
> 3 months
< 3 months
Highly sensitive
Unknown
Known
Present
Absent
1 focus
> 1 foci
Radioisotopes
The most important radiopharmaceuticals are:
89Sr (strontium-89 chloride);
153Sm (samarium-153 lexidronam);
and, to a lesser extent, 186Re (renium-186 etidronate).
There is no clear difference in treatment response between
89Sr, 153Sm and 186Re. However, there is a difference in onset
of response, duration of response and toxicity. For 153Sm and
186Re, the onset of response is rapid, but duration is shorter
than 89Sr.
89Sr
and 153Sm lexidronam are indicated for treatment of

bone pain, resulting from skeletal metastases involving more
than one site and associated with an osteoblastic response

on bone scan but without spinal cord compression (LE: 2,
GR: B). Overall, the response rate is 60-80%. However, pain
reduction is unlikely to occur within the first week, and can
occur as late as 1 month after injection. Analgesics should
therefore continue to be prescribed to patients until bone
pain improves.
If the pain responds to the initial treatment, administration of
153Sm lexidronam can be repeated at intervals of 8-12 weeks
in the presence of recurrent pain (LE: 2, GR: B).
Radiopharmaceuticals should not be administered if the
glomerular filtration rate is < 30 mL/min in patients who are
pregnant or who are breast feeding. Because of myelosuppression, a white blood cell count > 3500/L and a platelet
count > 100,000/L are desirable.
Post-operative pain management

Recommendations
Post-operative pain should be treated adequately to
avoid post-operative complications and the development of chronic pain.
Pre-operative assessment and preparation of the
patient allow in more effective pain management.
Adequate post-operative pain assessment can lead to
more effective pain control and fewer post-operative
complications.
GR
B
A
B
Specific pain treatment during ESWL

Table 5: Analgesic drug options during extra-corporeal
shock wave lithotripsy (ESWL)
Drug
Dosage
Alfentanil
0.5-1.0
mg/70 kg
1 g/kg
Fentanyl (or
sufentanil or
remifentanil)
Method of
administration
Intravenously
Frequency
(maximum)
On demand
Intravenously
On demand
(risk of
respiratory
depression)
Recommendations
GR
Analgesics should be given on demand during and
B
after ESWL because not all patients need pain relief.
Premedication with NSAIDs or midazolam often
B
decreases the need for opioids during the procedure.
Intravenous opioids and sedation can be used in com- C
bination during ESWL; dosage is limited by respiratory depression.
Post-ESWL, analgesics with a spasmolytic effect are
C
preferable.
ESWL = extracorporeal shock wave lithotripsy; NSAID = nonsteroidal anti-inflammatory drug.
Specific pain treatment after different urological

operations
Table 6: Analgesic drug options after transurethral
procedures
Drug
Dosage
(mg)
50
Method of
administration
Orally
100
Rectally
Metamizole
500-1000
Orally or iv
Paracetamol
500-1000
Orally or iv
Tramadol
50-100
Piritramid
15
Orally, im, sc
or iv
iv or sc
Pethidine
25-100
Orally, im, sc
Diclofenac
Frequency
(maximum)
Three times
daily
Every 16
hours
Four times
daily
Four times
daily
Four times
daily
Four times
daily
Four to six
times daily
iv = intravenously; im = intramuscularly; sc = subcutaneously.
Recommendations
Post-operative analgesics with a spasmolytic effect or
mild opioids are preferable.
Antimuscarinic drugs could be helpful in reducing
discomfort resulting from the indwelling catheter.
Antimuscarinic drugs may reduce the need for
opioids.
GR
C
B
B
Table 7: Analgesic drug options after laparoscopic

surgery, minor surgery of the scrotum, penis,
and inguinal region or transvaginal urological
surgery
Drug
Metamizole
Dosage
(mg)
500-1000
Paracetamol
500-1000
Tramadol
50-100
Morphine
10
Diclofenac
1 mg
bolus
50
100
Method of
Frequency
administration (maximum)
Orally or iv
Four times
daily
Orally or iv
Four times
daily
Orally, im, sc Four times
or iv
daily
Intermittent im Eight times
daily
iv
PCA, 5 minutes lockout
Orally
Three times
daily
Rectally
Every 16
hours
iv = intravenously; im = intramuscularly; sc = subcutaneously;

PCA = patient-controlled analgesia.
Recommendations
Low intra-abdominal pressure and good desufflation
at the end of the laparoscopic procedure reduces postoperative pain.
NSAIDS are often sufficient for post-operative pain
control.
NSAIDs decrease the need for opioids.
For post-operative pain control after minor surgery of
the scrotum, penis and inguinal region, multi-modal
analgesia with a combination of NSAIDs or paracetamol plus local anaesthetics should be used.
If possible, avoid opioids for out-patients.
NSAIDS are often sufficiently effective after minor or
moderate surgery.
GR
A
B
B
B
C
B
Table 8: Analgesic drug options after major perineal

open surgery, suprapubic extraperitoneal,
retroperitoneal or transperitoneal laparotomy
Drug
Dosage
Bupivacaine
0.25% + fentanyl 2 g/
mL
Morphine
5-15 mL/
hour
Metamizole
Paracetamol
1 mg
bolus
500-1000
mg
500-1000
mg
Method of
Frequency
administration (maximum)
Continuous
Not applicable
epidural infusion
iv
Orally or iv
Orally or iv
PCA, 5-minute
lockout
Four times
daily
Four times
daily
Tramadol
Piritramid
50-100
mg
15 mg
Orally, im, sc
or iv
iv or sc
50 mg
Orally
100 mg
Rectally
Four times
daily
Four times
daily
Three times
daily
Every 16
hours
iv = intravenously; im = intramuscularly; sc = subcutaneously;

PCA = patient-controlled analgesia.
Recommendations
GR
The most effective method for systemic administration A
of opioids is PCA, which improves patient satisfaction
and decreases the risk of respiratory complications.
Epidural analgesia, especially PCEA, provides superior A
post-operative analgesia, reducing complications and
improving patient satisfaction.
It is therefore preferable to systemic techniques.
PCA = patient-controlled analgesia; PCEA = patient-controlled

epidural analgesia.
Analgesics
Recommendations
Paracetamol can be very useful for post-operative pain
management as it reduces the consumption of opioids.
Paracetamol can alleviate mild post-operative pain as a
single therapy without major adverse effects.
NSAIDs are not sufficient as a sole analgesic agent
after major surgery.
NSAIDs are often effective after minor or moderate
surgery.
NSAIDs often decrease the need for opioids.
Avoid long-term use of COX inhibitors in patients
with atherosclerotic cardiovascular disease.
GR
B
B
B
B
B
B

Metamizole (dipyrone)
Metamizole is an effective antipyretic and analgesic drug
used for mild-to-moderate post-operative pain and renal
colic. Its use is prohibited in the USA and some European
countries because of single reported cases of neutropenia and
agranulo-cytosis. Dosage per day is 500-1000 mg four times
daily (orally, intravenously or rectally). If given intravenously, metamizole should be administered as a drip (1 g in 100
mL normal saline).
Table 9: Drug, administration, dosage and delivery

Drug
Method
of
administration
Single
dosage
(mg)
Frequency
Maximal
dosage
(mg/24
hours)
Paracetamol
Metamizole
Orally
Antipyretics
500Four times
1000
daily
iv
1000
Four times
daily
Rectally
1000
Four times
daily
Orally
5001000
1000
4000
(50mg/
kg)
4000
(50mg/
kg)
4000
(50mg/
kg)
4000
Four times
daily
iv
Four times 4000
daily
Conventional NSAIDs (i.e. non-selective COX inhibitors)
Ketorolac
Orally
10-30
Four times 40 orally
or iv
daily
90 iv or
im
60 iv or
im (elderly)
Ibuprofen
Orally
200Three times 2400
800
daily
Ketoprofen Orally
50
Four times 200
or iv
daily
Diclofenac
Orally
75
Twice daily 150
or iv
Orally
50
Three times 150
or iv
daily
Rectally
Meloxicam
Lornoxicam
Celecoxib
Parecoxib
100
Every 16
hours
COX-2 selective inhibitors
Orally
15
Once per
day
Orally
4
Three times
or iv
daily
Orally
100Once per
200
day
iv form 40
Once or
only
twice daily
Opioids
Strong opioids
Morphine** Orally or Starting Six to eight
rectally with 10 times daily
mg
Morphine** sc or im Starting Six to 12
with 5 times daily
mg
Morphine** iv
Starting Six to 12
with 2 times daily
mg
Pethidine
Orally,
25-150 Four times
(meperidine) sc or im
daily
Pethidine
Rectally 100
Four times
(meperidine)
daily
Pethidine
iv
25-100 Four times
(meperidine)
daily
Oxycodone Orally,
5-10
Four to six
iv or sc
times daily
Weak opioids
150
15
12
400
80
No maximal dose
No maximal dose
No maximal dose
500
500
500
400
Tramadol
Codeine
Orally
iv
Orally or
rectally
50
100
30-60
(plus
paracetamol)
Four to six
times daily
Four times
daily
400-600
300?
** A simple way of calculating the daily dosage of morphine for

adults (20-75 years) is: 100 patients age = morphine per day
in mg.
NSAID = non-steroidal anti-inflammatory drug; sc = subcutaneous; im = intramuscularly; iv = intravenously.
Table 10: Common equi-analgesic dosages for

parenteral and oral administration of
opioids*
Drug
Morphine
Fentanyl
Pethidine
Oxycodone
Dextropropoxyphene
Tramadol
Codeine
Parenteral (mg)
10
0.1
75
15
37.5
130
Oral (mg)
30
300
20-30
50
150
200
*All listed opioid doses are equivalent to parenteral morphine 10

mg. The intrathecal opioid dose is 1/100th, and the epidural dose
1/10th, of the dose required systemically.
Table 11: Typical patient-controlled analgesia (PCA)

dosing schedule
Drug
(concentration)
Morphine
(1 mg/mL)
Fentanyl
(0.01 mg/mL)
Pethidine
(10 mg/mL
Bolus size
0.5-2.5 mg
10-20 g
5-25 mg
Lockout
Continuous
interval (min) infusion
5-10
0.01-0.03
mg/kg/hour
5-10
0.5-0.1 g/
kg/hour
5-10
Recommendations
Intravenous PCA provides superior post-operative
analgesia, improving patient satisfaction and decreasing the risk of respiratory complications.
GR
A
Table 12: Typical epidural dosing schemes*

Drug
Single dose
Morphine
Fentanyl
Sufentanil
Pethidine
Bupivacaine 0.125%
or ropivacaine 0.2% +
fentanyl 2 g/mL
1-5 mg
50-100 g
10-50 g
10-30 mg
10-15 mL
Continuous
infusion
0.1-1 mg/hour
25-100 g/hour
10-20 g/hour
10-60 mg/hour
2-6 mL/hour
* L-bupivacaine doses are equivalent to those of bupivacaine.
Table 13: Typical patient-controlled epidural analgesia

(PCEA) dosing schemes
Drug
Morphine
Demand
dose
100-200 g
Fentanyl
10-15 g
Pethidine
30 mg
Bupivacaine 0.125% 2 mL
+ fentanyl 4 g/mL
Ropivacaine 0.2% + 2 mL
fentanyl 5 g/mL
Lockout Continuous
interval rate
10-15
300-600 g/
hour
6
80-120 g/
hour
30
10
4 mL/hour
20
5 mL/hour
Recommendations
GR
Epidural analgesia, especially PCEA, provides superior A
post-operative analgesia, reducing complications and
improving patient satisfaction. It is therefore preferable to systemic techniques.
Table 14: Examples of neural blocks

Procedure
Iliohypogastric or ilioinguinal
nerve infiltration after hernia
repair
Intercostal nerve infiltration
Continuous intrapleural
infusion
Dosage
Drug
10-20 mL Bupivacaine
or ropivacaine
0.25-0.5%
5-10 mL Bupivacaine
or ropivacaine
0.25-0.5%
10 mL/h Bupivacaine
or ropivacaine
0.1-0.2%
Recommendations
Multi-modal pain management should be employed
whenever possible since it helps to increase efficacy
while minimising adverse effects.
For post-operative pain control in out-patients, multimodal analgesia with a combination of NSAIDs or
paracetamol plus local anaesthetics should be used.
Multi-modal and epidural analgesia are preferable for
post-operative pain management in elderly patients
because these techniques are associated with fewer
complications.
Post-operative use of opioids should be avoided in
obese patients unless absolutely necessary.
GR
B
An epidural of local anaesthetic in combination with

B
NSAIDs or paracetamol is preferable in obese patients.
There are insufficient data to support a specifc postC
operative pain management plan for critically ill or
cognitively impaired patients.
Peri-operative pain management in children

Table 15: Pre-operative analgesia and sedation in
children
Drug
Morphine sulfate
Atropine
Dosage and route Action

of administration
0.1mg/kg
Can prevent crying,
which therefore reduces oxygen consumption and pulmonary
vasoconstriction
0.01-0.02 mg/kg Prevents bradycardia
iv, im, orally, or during induction of
anaesthesia
rectally
Pentobarbital
Ketamine
4-6 mg/kg im
6 mg/kg orally or
intranasally
Midazolam
0.5 mg/kg orally,
intranasally, or
rectally
Dexmedetomidine 4 g/kg orally or
intranasally
Clonidine
4g/kg orally
Chloral hydrate
50-100mg/kg
orally
Methoexital
25-30mg/kg rectally
EMLA
Lidocaine 2.5%;
prilocaine 2.5%
Pre-operative sedation
and separation anxiety
in children
Local application
decreases venepuncture pain
iv = intravenously; im = intramuscularly.
Table 16: Post-operative analgesia in children

Drug
Dosage
Paracetamol
10-15 mg/kg Orally, rectally

every 4 hours
20-30 mg/kg
every 6 hours
10-15 mg/kg Orally, iv, recevery 6 hours tally
Ibuprofen
Administration Severity
of
surgical
procedure
minor
minor
minor,
medium
Naproxen
6-8 mg/kg
Orally, iv, recevery 8-12
tally
hours
Codeine
0.5-1 mg/
Orally
kg every 3-4
hours
Morphine
0.1 mg/kg
0.3 mg/kg every
3-4 hours
every 2-4
iv, sc
hours
Infusion: 0.03 Orally
mg/kg/hour
Oxycodone
0.1-0.2 mg/kg Orally
every 3-4h
Hydromorphone 0.04-0.08 mg/ Orally
kg every 3-4
hours
Tramadol
1 mg/kg every iv
4-6 hours
Pethidine
2-3 mg/kg
iv
every 3-4
hours
iv = intravenously; sc = subcutaneously.
minor,
medium
minor,
medium
medium,
major
medium
medium
medium,
major
medium,
major
Patient-controlled analgesia can be used safely in children

more than 6 years old. In infants and children unable to use
PCA, nurse-controlled analgesia is effective. Locoregional
techniques such as wound infiltration, nerve blocks, caudal
and epidural analgesia are also used successfully.
Non-traumatic acute flank pain

Urological causes:
Renal or ureteral stones
Urinary tract infection (pyelonephritis, pyonephrosis, or
renal abscess)
Uretero-pelvic junction obstruction
Renal vascular disorders (renal infarction, renal vein
thrombosis)
Papillary necrosis
Intra- or peri-renal bleeding
Testicular cord torsion
Laboratory evaluation
All patients with acute flank pain require a urine test (red
and white cells, bacteria or urine nitrite), blood cell count,
and serum creatinine measurement. In addition, febrile
patients require C-reactive protein (CRP) and urine culture.
Pyelonephritis obstructive uropathy should be suspected
when the white blood count exceeds 15,000/mm3.
Recommendations on Diagnostic imaging
GR
Febrile patients (> 38C) with acute flank pain and/or B
with a solitary kidney need urgent imaging.
Unenhanced helical CT (UHCT) is the imaging
A
diagnostic modality with the highest sensitivity and
specificity for evaluation of non-traumatic acute flank
pain.
Ultrasound can be an alternative to UHCT in the ini- A
tial approach to non-traumatic acute flank pain.
Figure 2: Diagnostic approach to non-traumatic acute flank

pain
Acute Flank Pain
History, Physical examination, Temperature, Urinalysis Pain treatment
If not conclusive
Ultrasonography and/or unenhanced CT scan
Normal
+ normal
urinalysis
Non-urologic
flank pain
Refer patient
Normal +
abnormal
urinalysis
(Leukocyturia,
haematuria
or bacteriuria)
Genitourinary
abnormality
Non-Genitourinary
abnormality
Further
investigation
and appropriate
treatment
No hydronephrosis
No stone
Abnormal
Refer patient
Hydronephrosis
Stone
No stone
Stone
Ureteral obstruction
Check for :
Renal infarct
Renal abscess
Renal vein
thrombosis
Tumour
Cyst
Haematoma
Urinoma
Extrarenal
mass
No UTI
Stone
management
UTI
Treat
infection
Check for:
Ureteral tumour
Papillary necrosis
UPJ obstruction
Retroperitoneal
fibrosis
No UTI
Management to
relieve pain or
obstruction
UTI
Urinary
drainage and
infection
treatment
Stone
management
CT = computed tomography; UTI = urinary tract infection.

For a quick Differential Diagnosis and Management Options

the Decision tree (figure 2) is suggested:
Initial emergency treatment

Systemic analgesia
Pain relief is usually the first, most urgent, therapeutic step:
A a slow intravenous infusion of dipyrone, 1 g or 2 g, is
just as effective as diclofenac (75mg bolus) (LE: 1a).
Intravenous papaverine (120 mg)can effectively and safely
relieve patients not responding to conventional agents
(diclofenac) and can be an alternative to diclofenac in
patients with contraindications to NSAIDS (LE: 1b).
The combination of intravenous morphine + ketorolac
seems superior to either drug alone and appears to be
associated with a decrease in rescue analgesia.
Recommendation
NSAIDs such as diclofenac (75 mg, bolus), and dipyrone (1-2 g, slow intravenous injection) are both very
effective for acute flank pain.
GR
A
Upper urinary tract decompression

If pain relief cannot be achieved using medical therapy and
there are signs of infection and of impaired renal function,
upper urinary tract drainage should be carried out (Ureteral
stenting or percutaneous nephrostomy).
Indications for stenting for urgent relief of obstruction

Urine infection with urinary tract obstruction

Urosepsis
Intractable pain and/or vomiting
Obstruction of a solitary or transplanted kidney
Bilateral obstructing stones
Ureteral calculus obstruction in pregnancy
Aetiological treatment
Urolithiasis should be treated as defined in the EAU
Guidelines on Urolithiasis.
Infectious uncomplicated conditions (i.e. acute pyelonephritis in otherwise healthy individuals) should be treated with
appropriate antibiotics and analgesics.
When a diagnosis of UPJ obstruction, papillary necrosis,
renal infarction renal vein thrombosis, spontaneous renal
hemorrhage or testicular cord torsion has been made the
patient should be treated accordingly (see long version).
GUIDELINES ON CHRONIC PELVIC PAIN

(Complete text update February 2012)
D. Engeler (chairman), A.P. Baranowski, S. Elneil, J. Hughes,

E.J. Messelink, A. van Ophoven, P. Oliveira,
A.C. de C. Williams
Eur Urol 2004;46(6):681-9
Eur Urol 2010;57(1):35-48
This pocket version aims to synthesise the important clinical messages described in the full text and is presented as a
series of graded action based recommendations, which follow the standard for levels of evidence used by the EAU (see
Introduction chapter full text guidelines).
304 Chronic Pelvic Pain
Figure 1: an algorithm for diagnosing and managing CPP

Chronic Pelvic Pain
Physical
examination
History
yes
Specific disease associated pelvic pain
no
Pelvic pain syndrome
Treat according to specific

disease guidelines
Symptom of a well known

disease
Organ specific symptoms present
Go to: Pain management
no
yes
urology
see chapter 3
gynaecology
see chapter 4
gastro-enterology
see chapter 5
neurology
see chapter 6
sexology
see chapter 7
pelvic floor
see chapter 9
Figure 2: an algorithm for pain management

Multidisciplinary team
Holistic approach
Psychology
Physiotherapy
Pain medicine
see chapter 8
see chapter 9
see chapter 10
Chronic Pelvic Pain 305
Table 1: Classification of chronic pelvic pain syndromes

Axis I
Region
Chronic
pelvic
pain
Axis II
System
Specific
disease
associated
pelvic pain
Urological
OR
Pelvic pain
syndrome
Gynaecological
Gastrointestinal
Peripheral
nervers
Sexological
Psychological
Musculo-skeletal
Axis III
End organ as pain sundrome as identified from
Hx, Ex and Ix
Prostate
Bladder
Scrotal
Testicular
Epididymal
Penile Urethral
Post-vasectomy
Vulvar
Vestibular
Clitoral
Endometriosis associated
CPPS with cyclical exacerbations
Dysmenorrhoea
Irritable blowel
Chronic anal
Intermittent chronic anal
Pudendal pain syndrome
Dyspareunia
Pelvic pain with sexual dysfunction
Any pelvic organ
Pelvic floor muscle
Abdominal muscle
Spinal
Coccyx
Axis IV
Axis V
Referral
Temporal
characteristics characteristics
Suprapubic
ONSET
Inguinal
Acute
Urethral
Chronic
Penile/clitoral
Perineal
ONGOING
Rectal
Sporadic
Back
Cyclical
Buttocks
Continuous
Thighs
TIME
Filling
Emptying
Immediate
post
Late post
TRIGGER
Provoked
Spontaneous
Axis VI
Character
Aching
Burning
Stabbing
Electric
Axis VII
Associated
symptoms
UROLOGICAL
Frequency
Nocturia
Hesitance
Dysfunctional flow
Urge
Incontinence
GYNAECOLOGICAL
Menstrual
Menopause
GASTROINTESTINAL
Constipation
Diarrhoea
Bloatedness
Urge
Incontinence
NEUROLOGICAL
Dysaesthesia
Hyperaesthesia
Allodynia
Hyperalegesie
Axis VIII
Psychological
symptoms
ANXIETY
About pain
or putative
cause of pain
Catastrophic thinking about pain
DEPRESSION
Attributed to
pain or impact
of pain
Attributed to
other causes
Unattributed
PTSD
SYMPTOMS
Re-experiencing
Avoidance
SEXUOLOGICAL
Satisfaction
Female dyspareunia
Sexual avoidance
Erectile dysfunction
Medication
MUSCLE
Function impairment
Fasciculation
CUTANEOUS
Trophic changes
Sensory changes
Figure 3: phenotyping and assessment algorithm for CPP

Phenotyping
Assessment
Urology
Urinary flow, micturition diary, cystoscopy, ultrasound, uroflowmetry
Psychology
History of negative experiences, important loss, coping mechanism, depression
Organ specific
Ask for gynaecological, gastro-intestinal, ano-rectal, sexological complaints

Gynaecological examination, rectal examination
Infection
Semen culture and urine culture, vaginal swab, stool culture
Neurological
Ask for neurological complaints (sensory loss, dysaesthesia).

Neurological testing during physical examination: sensory problems, sacral reflexes and muscular function
Tender muscle
Palpation of the pelvic floor muscles, the abdominal muscles and the gluteal muscles
UROLOGICAL ASPECTS OF CHRONIC PELVIC PAIN

PROSTATE PAIN SYNDROME
Recommendations: assessment and diagnosis
prostate pain syndrome (PPS)
GR
Specific diseases with similar symptoms must be

A
excluded. It is therefore recommended to adapt diagnostic procedures to the patient and to aim at identifying them.
After primary exclusion of specific diseases, patients A
with symptoms according to the above definition
should be diagnosed with PPS.
B
A validated symptom and quality of life scoring
instrument, such as the NIH-CPSI, should be considered for initial assessment as well as for follow-up.
It is recommended to assess PPS associated negative

cognitive, behavioural, sexual, or emotional consequences, as well as symptoms of lower urinary tract
and sexual dysfunctions.
Recommendations: treatment of prostate pain

syndrome (PPS)
GR
Consider multimodal and phenotypically directed

treatment options for PPS.
Alpha-blockers are recommended for patients with a
duration of PPS < 1 year.
Single use of antimicrobial therapy (quinolones or
tetracyclines) is recommended in treatment-nave
patients over a minimum of 6 weeks with a duration
of PPS < 1 year.
NSAIDs are recommended for use in PPS, but longterm side effects have to be considered.
Allopurinol is not recommended for use in PPS.
Phytotherapy might be used in patients with PPS.
Consider high-dose pentosan polysulphate to
improve symptoms and quality of life in PPS.
Pregabalin is not recommended for use in PPS.
Perineal extracorporeal shock wave therapy might be
considered for the treatment of PPS.
Electroacupuncture might be considered for the treatment of PPS.
Posterior tibial nerve stimulation might be considered
for the treatment of PPS.
TUNA of the prostate is not recommended for the
treatment of PPS.
B
A
A
B
B
B
A
A
B
B
B
B
For PPS with significant psychological distress,

psychological treatment focussed on PPS should be
attempted.
Figure 4: assessment and treatment algorithm for PPS

Assessment
Treatment
Urine culture
Grade A recommended
Alpha-blockers when duration is < 1 year

Single use antibiotics (6 weeks) when duration is < 1 year
Uroflowmetry
High dose Pentosan polysulfate to improve QoL and symptoms
Transrectal US
prostate
NIH-CPSI scoring
list
Grade B recommended
NSAID s. Be aware of long-term side effects

Phytotherapy
Phenotyping
Perineal extracorporeal shockwave therapy
Pelvic floor muscle

testing
Electroacupuncture
Percutaneous tibial nerve stimulation (PTNS)
Psychological treatment focused on the pain
Not recommended
Allopurinol
[B]
Pregabalin
[A]
TransUrethral Needle Ablation (TUNA)
[B]
BLADDER PAIN SYNDROME

Table 2: ESSIC classification of types of BPS according to
the results of cystoscopy with hydrodistension and biopsies
Cystoscopy with hydrodistension
Hunners
Not Normal
Glomerulationsa
lesionb
done
Biopsy
Not done
Normal
Inconclusive
Positivec
XX
XA
XB
XC
1X
1A
1B
1C
2X
2A
2B
2C
3X
3A
3B
3C
aCystoscopy:
glomerulations grade 23
per Falls definition with/without glomerulations
cHistology showing inflammatory infiltrates and/or detrusor
mastocytosis and/or granulation tissue and/or intrafascicular
fibrosis
bLesion
Recommendations: assessment and diagnosis

bladder pain syndrome (BPS)
GR
Specific diseases with similar symptoms have to be

A
excluded. It is therefore recommended to adapt diagnostic procedures to each patient and aim at identifying them.
After primary exclusion of specific diseases, patients A
with symptoms according to the above definition
should be diagnosed with BPS by subtype and phenotype.
A validated symptom and quality of life scoring

instrument should be considered for initial assessment as well as for follow-up.
BPS associated non bladder diseases should be
assessed systematically.
BPS associated negative cognitive, behavioural, sexual, or emotional consequences should be assessed.
Recommendations
GR
Subtype and phenotype-oriented therapy for BPS is

recommended.
Multimodal behavioural, physical and psychological
techniques should always be considered alongside
oral or invasive treatments for BPS.
Opioids might be used in BPS in disease flare-ups.
Long term application solely if all treatments failed.
Corticosteroids are not recommended as long-term
treatment.
Hydroxyzine is recommended for use in BPS.
Consider cimetidine as valid oral option before invasive treatments.
Amitriptyline is recommended for use in BPS.
Oral PPS is recommended for use in BPS.
Treatment with oral PPS plus subcutaneous heparin
is recommended especially in low responders to PPS
alone.
Antibiotics can be offered when infection is present
or highly suspected.
Prostaglandins are not recommended. Insufficient
data on BPS, adverse effects considerable.
A
A
C
C
A
B
A
A
A
C
C
Cyclosporin A might be used in PPS but adverse

effects are significant and should be carefully considered.
Duloxetin is not recommended for BPS treatment.
Oxybutynin might be considered for the treatment
of BPS.
Gabapentin might be considered in oral treatment of
BPS.
Consider intravesical lidocain plus sodium bicarbonate prior to more invasive methods.
Consider intravesical PPS before more invasive treatment alone or combined with oral PPS.
Consider intravesical heparin before more invasive
measures alone or in combination treatment.
Consider intravesical hyaluronic acid before more
invasive measures.
Consider intravesical chondroitin sulphate before
more invasive measures.
Consider intravesical DMSO before more invasive
measures.
Consider intravesical bladder wall and trigonal injection of BTX-A if intravesical instillation therapies
failed.
Consider submucosal injection of BTX-A plus hydrodistension if intravesical instillation therapies failed.
Intravesical therapy with Bacillus Calmette Gurin is
not recommended in BPS.
Intravesical therapy with clorpactin is not recommended in BPS.
Intravesical therapy with vanilloids is not recommended in BPS.
C
C
C
A
A
C
B
B
A
C
A
A
A
C
Bladder distension is not recommendedas atreatment

of BPS.
Electromotive drug administration might be considered before more invasive measures.
Consider transurethral resection (or coagulation or
laser) of bladder lesions, but in BPS type 3 C only.
Neuromodulation might be considered before more
invasive interventions.
Consider bladder training in patients with little pain.
Consider manual and physical therapy in first
approach.
Consider in diet avoidance of triggering substances.
Accupuncture is not recommended.
Consider psychological therapy in multimodal
approach.
All ablative organ surgery should be last resort for
experienced and BPS knowledgeable surgeons only.
PPS = pentosanpolysulphate sodium; DMSO = dimethyl
sulphoxide.
C
C
B
B
B
B
C
C
B
A
Figure 5: diagnosis and therapy of BPS

Assessment
Treatment
Urine culture
Grade A recommended
Standard: Hydroxyzine, Amitriptyline, Pentosanpolysulphate

Intravesical: PPS, DMSO, onabotulinum toxin A plus hydrodistension
Uroflowmetry
Cystoscopy with
hydrodistension
Bladder biopsy
Grade B recommended
Oral: Cimetidine , cyclosporin A

Intravesical: hyaluronic acid, chondroitin sulphate
Micturition diary
Electromotive drug administration for intravesical drugs
Pelvic floor muscle

testing
Neuromodulation, bladder training, physical therapy

Psychological therapy
Phenotyping
ICSI score list
Not recommended
Bacillus Calmette Guerin

Intravesical Chlorpactin
Other comments
Data on surgical treatment are largely variable

Coagulation and laser only for Hunners lesions
Figure 6: algorithm for BPS Type 3 C

Bladder Pain Syndrome
Hunner lesion at cystoscopy
yes
no
TUR / laser
Adequate:
Inadequate:
* Retreat when necessary
* Start other treatment
* Oral agents
* TENS
* Complimentary medicine
Inadequate relief:
* start Intravesical therapy
Still inadequate response:

* Refer to specialist
pain management unit
GENITAL PAIN SYNDROME

Recommendations: treatment of genital pain
syndrome
GR
We recommend to start with general treatment

options for chronic pelvic pain (see chapter 10).
We recommend informing about the risk of postvasectomy pain when counselling patients planned
for vasectomy.
To reduce the risk of scrotal pain, we recommend
open instead of laparoscopic inguinal hernia repair.
We recommend that during inguinal hernia repair all

the nerves in the spermatic cord are identified.
For patients who are treated surgically, we recommend microsurgical denervation of the spermatic
cord.
For patients who do not benefit from denervation we
recommend to perform epididymectomy.
We recommend that orchiectomy is reserved as last
resort when every other treatment has failed.
A
A
B
C
Figure 7: assessment and treatment algorithm for scrotal

pain syndrome
Assessment
Treatment
Semen culture
Grade A recommended
General treatment options for chronic pelvic pain - chapter 10

Microsurgical denervation of the spermatic cord
Uroflowmetry
Inform patients undergoing vasectomy about the risk of pain
Ultrasound
scrotum (see text)
For surgeons: open hernia repair yields less scrotal pain

For surgeons: identify all nerves during hernia repair
Pelvic floor muscle

testing
Phenotyping
Grade B recommended
Other comments
Epididymectomy, in case patient did not benefit from denervation
Orchiectomy is a last resort option, when everything else has failed

Ultrasound has no clinical implications on the further treatment
although physicians tend to still use ultrasound to reassure the patient
URETHRAL PAIN SYNDROME

Recommendations: treatment of urethral pain
syndrome
GR
We recommend to start with general treatment

options for chronic pelvic pain (see chapter 10).
We recommend that patients with urethral pain syndrome are treated in a multidisciplinary and multimodal programme.
A
B
When patients are distressed, we recommend referring them for pain-relevant psychological treatment
to improve function and quality of life.
Figure 8: assessment and treatment algorithm for urethral

pain syndrome
Assessment
Treatment
Uroflowmetry
Grade A recommended
General treatment options for chronic pelvic pain - chapter 10
Micturition diary
Pelvic floor muscle
testing
Grade B recommended
Treat in a multidisciplinary and multimodal programme

Pain-relevant psychological treatment to improve QoL and function
Phenotyping
Other comments
Data on urethral pain are very sparse and of limited quality
GYNAECOLOGICAL ASPECTS OF CHRONIC PELVIC PAIN

Recommendations: gynaecological aspects of
chronic pelvic pain
GR
All women with pelvic pain should have a full gynaecological history and evaluation, and including laparoscopy is recommended to rule out a treatable cause
(e.g. endometriosis).
Provide therapeutic options such as hormonal therapy or surgery in well-defined disease states.
Provide a multidisciplinary approach to pain management in persistent disease states.
Recommend psychological treatment for refractory
chronic vulvar pain.
Use alternative therapies in the treatment of chronic
gynaecological pelvic pain.
B
B
B
C
Figure 9: assessment and treatment algorithm gynaecological aspects in chronic pelvic pain
Assessment
Treatment
Gynaecological
examination
Grade A recommended
Laparoscopy to rule out treatable causes
Ultrasound
Laparoscopy (see
text)
Grade B recommended
Hormonal therapy in well defined states

Multidisciplinary approach in persistent disease states
Psychological treatment for refractory chronic vulvar pain
GASTROINTESTINAL ASPECTS OF CHRONIC PELVIC PAIN

Recommendations for functional anorectal pain
GR
Functional testing is recommended in patients with

anorectal pain.
Biofeedback treatment is recommended in patients
with pelvic pain and dyssynergic defecation.
Botulinum toxin and electrogalvanic stimulation can
be considered in the chronic anal pain syndrome.
Sacral neuromodulation is recommended in the
chronic anal pain syndrome.
Diltiazem is recommended in the intermittent chronic anal pain syndrome.
A
A
B
C
C
Figure 10: assessment and treatment algorithm for anorectal pain syndrome
Assessment
Treatment
Endoscopy
Grade A recommended
Biofeedback treatment
Pelvic floor muscle

testing
Anorectal
manometry
Botulinum toxine A in women with pelvic pain
Grade B recommended
Electro-galvanic stimulation
Rectal balloon
expulsion test
Sacral neuromodulation should be considered
Other comments
MRI-defecography
Diltiazem should be considered in intermittent anal pain syndrome
Figure 11: diagnosis algorithm for chronic anorectal pain

Chronic anorectal pain
Endoscopy normal
yes
no
Tenderness of puborectalis muscle
yes
no
* Anorectal manometry
* Balloon expulsion test
* MRI-Defecography
Anorectal pain syndrome
Dysfunction present
yes
no
* Biofeedback
* Electro stimulation
Refer to specialist
pain management unit
Specific disease guidelines
PERIPHERAL NERVE PAIN SYNDROMES

Recommendations: pudendal neuralgia
GR
It is important to rule out confusable diseases.

If a peripheral nerve pain syndrome is suspected,
early referral should occur to an expert in the field,
working within a multidisciplinary team environment.
Imaging and neurophysiology may help with the
diagnosis, but the gold standard investigation is an
image and nerve locator guided local anaesthetic
injection.
Neuropathic pain guidelines are well established.
Standard approaches to management of neuropathic
pain should be utalised.
A
B
Figure 12: assessment and treatment algorithm for peripheral nerve pain syndrome
Assessment
Treatment
Extended
neurological tests
Grade A recommended
Extended history
on nature of pain
Standardised
questionnaires
Grade B recommended
Refer to an expert when a peripheral nerve problem is suspected
Imaging may be of help

Neurophysiology may be of help
Treatment is as for any other nerve injury
SEXOLOGICAL ASPECTS OF CHRONIC PELVIC PAIN

Recommendations: sexological aspects of chronic GR
pelvic pain
Clinicians may screen for abuse in patients present- B
ing with symptoms suggestive for prostate pain
syndrome, but should not assume the pain is psychological.
The biopsychosocial model should be applied in the

evaluation of the effect of prostate pain syndrome on
the sexual function of the patient.
The biopsychosocial model should be incorporated in
research in the role of chronic pelvic pain in sexual
dysfunction.
Behavioral strategies should be offered to the patient
and his/her partner to cope with sexual dysfunctions.
We recommend training of the pelvic floor muscles
to improve quality of life and sexual function.
B
B
Figure 13: assessment and treatment algorithm for sexologial aspects in chronic pelvic pain
Assessment
Treatment
History of sexual
functioning
Grade A recommended
Refer to sexologist when sexual dysfunction or trauma is present
History of negative
experiences
Ask about abuse
Grade B recommended
Screen for sexual abuse

Use a bio-psycho-social model in treating the pain
Psychiatric history
History of
relationship
Offer behavioral strategies to cope with sexual dysfunctions

Offer partner treatment
Refer for pelvic floor physiotherapy
PSYCHOLOGICAL ASPECTS OF CHRONIC PELVIC PAIN

Recommendations: psychological aspects of
chronic pelvic pain
GR
Psychological distress is common in pelvic pain in

women but should be interpreted in the context of
pain.
We recommend asking the patient what she thinks
may be wrong to cause pain, to allow the opportunity to inform and reassure as appropriate.
We recommend trying psychological interventions

in combination with medical and surgical treatment,
or alone.
Figure 14: assessment and treatment algorithm for psychological aspects of chronic pelvic pain
Assessment
Treatment
Psychological
history
Grade A recommended
Investigate painrelated beliefs and

behavior
Interpret psychological distress in the context of pain

Psychological interventions as adjuvant to other modalities
Grade B recommended
Ask the patient what he or she believes may be the problem that
causes the pain
PELVIC FLOOR FUNCTION AND CHRONIC PELVIC PAIN

Recommendations: pelvic floor function
GR
We recommend the use of the ICS classification on

pelvic floor muscle function and dysfunction.
In patients with chronic pelvic pain syndrome we
suggest to actively look for the presence of myofascial trigger points.
In patients with chronic pelvic pain syndrome we
suggest to apply pelvic floor muscle treatment as
first line treatment.
In patients with an overactive pelvic floor we recommend biofeedback as therapy adjuvant to muscle
exercises.
When myofascial triggerpoints are found we recommend treatment by pressure or needling.
A
B
Figure 15: assessment and treatment pelvic floor function

Assessment
Treatment
Palpation of the
muscles
Grade A recommended
Use the International Continence Society classification of dysfunction

Use biofeedback in combination with muscle exercises
Testing of pelvic
floor function
Treat myofascial triggerpoints using pressure or needling
Pelvic floor muscle

EMG
Test for myofascial
Triggerpoints
Grade B recommended
Look actively for the presence of myofascial trigger points

Apply pelvic floor muscle therapy as first line treatment
History of all the

involved organs
Standardised
questionnaires
Other comments
The role and options of a physiotherapist may differ between countries
GENERAL TREATMENT OF CHRONIC PELVIC PAIN

Recommendations: general treatment of chronic
pelvic pain
All other reasonable treatments must have been tried
and failed.
The decision to instigate long-term opioid therapy
should be made by an appropriately trained specialist
in consultation with another physician (including the
patients and their family doctor).
Where there is a history or suspicion of drug abuse,
a psychiatrist or psychologist with an interest in pain
management and drug addiction should be involved.
The patient should undergo a trial of opioids.
The dose required needs to be calculated by careful
titration.
GR
A
A
The patient should be made aware (and possibly give

written consent):
That opioids are strong drugs and associated with
addiction and dependency.
Opioids will normally only be prescribed from one
source (preferably the family doctor).
The drugs will be prescribed for fixed periods of
time and a new prescription will not be available
until the end of that period.
The patient may be subjected to spot urine and possibly blood checks to ensure that the drug is being
taken as prescribed, and that non-prescribed drugs
are not being taken.
Inappropriate aggressive behaviour associated with
demanding the drug will not be accepted.
Hospital specialist review will normally occur at
least once a year.
The patient may be requested to attend a psychiatric/psychological review.
Failure to comply with the above may result in the
patient being referred to a drug dependency agency
and the use of therapeutic, analgesic opioids being
stopped.
Morphine is the first-line drug, unless there are contraindications to morphine or special indications for
another drug.
The drug should be prescribed in a slow-release/
modified release form.
Short-acting preparations are undesirable and
should be avoided where possible.
Parenteral dosing is undesirable and should be
avoided where possible.
A
A
A
Recommendations: medical treatment of chronic pelvic

pain
Agent
Paracetamol
NSAIDs
Pain Type
LE
Somatic pain 1a
Pelvic pain
1a
with inflammatory
process (e.g.
dysmenorrhoea)
1a
Central
mechanisms (e.g.
endometriosis)
Antidepressants
Neuropathic 1a
including tricyclic pain
antidepressants,
venlafaxine and
duloxetine
Anticonvulsants
Neuropathic 1a
gabapentin, prepain, fibrogabalin
myalgia
Gabapentin
Women with 2b
chronic pelvic pain
Gr
A
Comment
Evidence
based on
arthritic pain
with good
benefit
Good evidence for
their use
No good
evidence for
their use
Effective.
No specific
evidence for
chronic pelvic pain
Effective
Effective
Topical capsaicin
Neuropathic 1a
pain
Opioids
Chronic
non-malignant pain
1a
Nerve blocks
TENS
1a
Neuromodulation Pelvic pain
Some evidence of
benefit
Beneficial
in a small
number of
patients
Have a role
as part of a
broad management
plan
No good
evidence of
benefit
Role developing with
increasing
research.
Figure 16: algorithm for the use of neuropathic analgesics

Assessment
Treatment
General history
Grade A recommended
Paracetamol in somatic pain

NSAID s when inflammation is present
Medications used
Antidepressants (including TCA) in neuropathic pain
Allergic reactions
Anticonvulsants in neuropathic pain
Use of alcohol
Topical Capsaicin in neuropathic pain

Opiods in chronic non-malignant pain
Daily activities that

will be effected
Grade B recommended
Other comments
Nerve blocks as part of a broad management plan
[C]
Neuromodulation may become an option, increasing research
[C]
Association of Urology at their website - http://www.uroweb.org.
GUIDELINES ON UROLITHIASIS
(Update February 2012)
C. Trk (chairman), T. Knoll (vice-chairman), A. Petrik,

K. Sarica, C. Seitz, M. Straub
Epidemiology
Between 1,200 and 1,400 per 100,000 will develop urinary
stones each year with a male/female ratio of 3:1. A number
of known factors of influence to the development of stones
are discussed in more detail in the extended version of the
Urolithiasis guidelines.
Classification of stones
Correct classification of stones is important since it will
impact treatment decisions and outcome.
Urinary stones can be classified according to the following
aspects: stone size, stone location, X-ray characteristics
of stone, aetiology of stone formation, stone composition
(mineralogy), and risk group for recurrent stone formation
(Tables 1-3).
Urolithiasis 329
Table 1: X-ray characteristics

Radiopaque
Calcium oxalate
dihydrate
Calcium oxalate
monohydrate
Calcium phosphates
Poor radiopaque
Magnesium
ammonium phosphate
Apatite
Radiolucent
Uric acid
Cystine
Xanthine
Ammonium urate
2,8-dihydroxyadenine
Drug-stones
Table 2: Stones classified according to their aetiology

Non infection stones
Calcium
oxalates
Calcium
phosphates
Uric acid
Infection
stones
Magnesium
ammonium
phosphate
Apatite
Genetic
stones
Cystine
Drug stones
Xanthine
Ammonium
urate
e.g. Indinavir
(see extended
document)
Table 3: Stones classified by their composition

Chemical composition
Calcium oxalate monohydrate
Calcium-oxalate-dihydrate
Uric acid dihydrate
Ammonium urate
330 Urolithiasis
Mineral
whewellite
wheddelite
uricite
Magnesium ammonium phosphate

Carbonate apatite (phosphate)
Calcium hydrogenphosphate
Cystine
Xanthine
Drug stones
struvite
dahllite
brushite
Risk groups for stone formation

The risk status of a stone former is of particular interest as it
defines both probability of recurrence or (re)growth of stones
and is imperative for pharmacological treatment.
Table 4: High risk stone formers

General factors
Early onset of urolithiasis in life (especially children and
teenagers)
Familial stone formation
Brushite containing stones (calcium hydrogen phosphate;
CaHPO4.2H2O)
Uric acid and urate containing stones
Infection stones
Solitary kidney (The solitary kidney itself does not present
an increased risk of stone formation, but prevention of
stone recurrence is more important)
Diseases associated with stone formation
Hyperparathyroidism
Nephrocalcinosis
Gastrointestinal diseases or disorders (e.g. jejuno-ileal
bypass, intestinal resection, Crohns disease, malabsorptive
conditions, enteric hyperoxaluaria after urinary diversion)
Urolithiasis 331
Sarcoidosis
Genetically determined stone formation
Cystinuria (type A, B, AB)
Primary hyperoxaluria (PH)
Renal tubular acidosis (RTA) type I
Xanthinuria
Lesh-Nyhan-Syndrome
Cystic fibrosis
Drugs associated with stone formation (see Chapter 11
extended text)
Anatomical abnormalities associated with stone formation
Medullary sponge kidney (tubular ectasia)
UPJ obstruction
Calyceal diverticulum, calyceal cyst
Ureteral stricture
Vesico-uretero-renal reflux
Horseshoe kidney
Ureterocele
DIAGNOSIS
Diagnostic imaging
Standard evaluation of a patient includes taking a detailed
medical history and physical examination. The clinical diagnosis should be supported by an appropriate imaging procedure.
332 Urolithiasis
Recommendation
LE
GR
With fever or solitary kidney, and when diagnosis is doubtful, immediate imaging is indicated.
A*

If available, ultrasonography, should be used as the primary diagnostic imaging tool although pain relief, or any
other emergency measures should not be delayed by imaging assessments. KUB should not be performed if NCCT is
considered; however, it is helpful in differentiating between
radiolucent and radiopaque stones and for comparison during follow-up.
Evaluation of patients with acute flank pain

Non-contrast enhanced computed tomography (NCCT) has
become the standard for diagnosis of acute flank pain since it
has higher sensitivity and specificity than IVU.
Recommendation
LE
NCCT should be used to confirm stone diag1a

nosis in patients with acute flank pain, because
it is superior to IVU
GR
A
Indinavir stones are the only stones not detectable on NCCT.
Recommendation
A renal contrast study (enhanced CT or IVU)
is indicated when planning treatment for renal
stones.
LE
GR
A*
Urolithiasis 333
Biochemical work-up
Each emergency patient with urolithiasis needs a succinct
biochemical work-up of urine and blood besides the imaging
studies. At that point no difference is made between highand low-risk patients.
Recommendations: Basic analysis emergency stone

patient
Urine
Urinary sediment/dipstick test out of spot urine sample for: red cells / white cells / nitrite / urine pH level
by approximation
Urine culture or microscopy
Blood
Serum blood sample creatinine / uric acid / ionized
calcium / sodium / potassium / CRP
Blood cell count
If intervention is likely or planned: Coagulation test
(PTT and INR)
GR
A*
A
A*
A*
A*
Examination of sodium, potassium, CRP, and blood coagulation time can be omitted in the non-emergency stone patient.
Patients at high risk for stone recurrences should undergo a
more specific analytical programme (see section MET below).
Analysis of stone composition should be performed in all
first-time stone formers (GR: A). It should be repeated in
case of:
Recurrence under pharmacological prevention
334 Urolithiasis
Early recurrence after interventional therapy with complete stone clearance

Late recurrence after a prolonged stone-free period
(GR: B)
The preferred analytical procedures are:
X-ray diffraction (XRD)
Infrared spectroscopy (IRS)
Wet chemistry is generally deemed to be obsolete.
Acute treatment of a patient with renal colic

Pain relief is the first therapeutic step in patients with an
acute stone episode.
Recommendations for pain relief during and LE

prevention of recurrent renal colic
GR
First choice: start with an NSAID, e.g.

1b A
diclofenac*, indomethacin or ibuprofen.
Second choice: hydromorphine, pentazocine
4
C
and tramadol.
Diclofenac sodium* / alpha-blocker** is
1b A
recommended to counteract recurrent pain
after ureteral colic.
Third-line treatment:
Spasmolytics (metamizole sodium etc.) are
alternatives which may be given in circumstances in which parenteral administration of a
non-narcotic agent is mandatory.
GFR = glomerular filtration rate; NSAID = non-steroidal antiinflammatory drug.
*Caution: Diclofenac sodium affects GFR in patients with
reduced renal function, but not in patients with normal renal
function (LE: 2a). ** (see extended document section 5.3)
Urolithiasis 335
If pain relief cannot be achieved by medical means, drainage, using stenting or percutaneous nephrostomy, or stone
removal, should be carried out.
Management of sepsis in the obstructed kidney

The obstructed, infected kidney is a urological emergency.
Recommendations
LE
GR
For sepsis with obstructing stones, the collecting system should be urgently decompressed,
using either percutaneous drainage or ureteral
stenting.
Definitive treatment of the stone should be
delayed until sepsis is resolved.
1b
1b
In exceptional cases, with severe sepsis and/or the formation

of abscesses, an emergency nephrectomy may become necessary.
Further Measures - Recommendations

Collect urine for antibiogram following decompression.
Start antibiotics immediately thereafter (+ intensive
care if necessary).
Revisit antibiotic treatment regimen following antibiogram findings.
* Upgraded based on panel consensus.
336 Urolithiasis
GR
A*
Stone relief
When deciding between active stone removal and conservative treatment using MET, it is important to consider all the
individual circumstances of a patient that may affect treatment decisions.
Observation of ureteral stones

Recommendations
LE
In patients with newly diagnosed ureteral

1a
stones < 10 mm, and if active stone removal is
not indicated, observation with periodic evaluation is optional initial treatment.
Such patients may be offered appropriate medical therapy to facilitate stone passage during
the observation period*.
*see also Section MET.
GR
A
Observation of kidney stones

It is still debatable whether kidney stones should be treated,
or whether annual follow-up is sufficient for asymptomatic
caliceal stones that have remained stable for 6 months.
Recommendations
GR
Kidney stones should be treated in case of growth,

A
formation of de novo obstruction, associated infection, and acute and/or chronic pain.
Comorbidity and patient preference need to be taken C
into consideration when making treatment decisions.
A
If kidney stones are not treated, periodic evaluation
is needed.
* Upgraded following panel consensus.
Urolithiasis 337
Medical expulsive therapy (MET)

For patients with ureteral stones that are expected to pass
spontaneously, NSAID tablets or suppositories (i.e. diclofenac
sodium, 100-150 mg/day, over 3-10 days) may help to reduce
inflammation and the risk of recurrent pain.
Alpha-blocking agents, given on a daily basis, reduce recurrent colic (LE: 1a). Tamsulosin, has been the most commonly used alpha blocker in studies.
Recommendations for MET
LE
For MET, alpha-blockers or nifedipine are recommended.

Patients should be counselled about the attendant risks of MET, including associated drug
side effects, and should be informed that it is
administered as off-label use.
Patients, who elect for an attempt at spontaneous passage or MET, should have well-controlled pain, no clinical evidence of sepsis, and
adequate renal functional reserve.
Patients should be followed to monitor stone
4
position and to assess for hydronephrosis.
MET in children cannot be recommended due 4
to the limited data in this specific population.
Statements
GR
A
A*
A*
C
LE
MET has an expulsive effect also on proximal ureteral 1b
stones.
338 Urolithiasis
After SWL for ureteral or renal stones, MET seems to 1a

expedite and increase stone-free rates, reducing additional analgesic requirements.
Based on studies with a limited number of patients,
1b
no recommendation for the use of corticosteroids
in combination with alpha-blockers in MET can be
made.
Chemolytic dissolution of stones

Oral or percutaneous irrigation chemolysis of stones can be
a useful first-line therapy or an adjunct to SWL, PNL, URS,
or open surgery to support elimination of residual fragments.
However, its use as first-line therapy may take weeks to be
effective.
Percutaneous irrigation chemolysis

Recommendations
GR
In percutaneous chemolysis, at least two nephrosto- A

my catheters should be used to allow irrigation of the
renal collecting system, while preventing chemolytic
fluid draining into the bladder and reducing the risk
of increased intrarenal pressure*.
Pressure- and flow-controlled systems should be used
if available.
* Alternatively, one nephrostomy catheter with a JJ stent and
bladder catheter can serve as a through-flow system preventing
high pressure.
Urolithiasis 339
Methods of percutaneous irrigation chemolysis

Stone
composition
Struvite
Carbon apatite
Irrigation solution
Comments
10% Hemiacidrin,
pH 3.5-4
Subys G
Combination with
SWL for staghorn
stones
Risk of cardiac
arrest due to
hypermagnesaemia
Can be considered
for residual fragments
Takes significantly longer time
than for uric acid
stones
Used for elimination of residual
fragments
Oral chemolysis
is the preferred
option
Brushite
Hemiacidrin
Subys G
Cystine
Trihydroxymethylaminomethan
(THAM; 0.3 or 0.6
mol/L), pH 8.5-9.0
N-acetylcysteine
(200 mg/L)
Uric acid
Trihydroxymethylaminomethan
(THAM; 0.3 or 0.6
mol/L), pH 8.5-9.0
Oral Chemolysis
Oral chemolitholysis is efficient for uric acid calculi only.
The urine pH should be adjusted to between 7.0 and 7.2.
340 Urolithiasis
Recommendations
GR
The dosage of alkalising medication must be modified A

by the patient according to the urine pH, which is a
direct consequence of the alkalising medication.
Dipstick monitoring of urine pH by the patient is
A
required at regular intervals during the day. Morning
urine must be included.
The physician should clearly inform the patient of
A
the significance of compliance.
SWL
The success rate for SWL will depend on the efficacy of the
lithotripter and on:
size, location (ureteral, pelvic or calyceal), and composition (hardness) of the stones;
patients habitus;
performance of SWL.
Contraindications of SWL
Contraindications to the use of SWL are few, but include:
pregnancy;
bleeding diatheses;
uncontrolled urinary tract infections;
severe skeletal malformations and severe obesity, which
prevent targeting of the stone;
arterial aneurism in the vicinity of the stone;
anatomical obstruction distal of the stone.
Urolithiasis 341
Stenting prior to SWL

Kidney stones
A JJ stent reduces the risk of renal colic and obstruction, but
does not reduce formation of steinstrasse or infective complications.
Recommendation - stenting & SWL
LE
Routine stenting is not recommended as part of 1b

SWL treatment of ureteral stones.
GR
A
Best clinical practice (best performance)

Pacemaker
Patients with a pacemaker can be treated with SWL, provided
that appropriate technical precautions are taken; patients
with implanted cardioverter defibrillators must be managed
with special care (firing mode temporarily reprogrammed
during SWL treatment). However, this might not be necessary with new-generation lithotripters.
Recommendation - Shock wave rate
LE
GR
The optimal shock wave frequency is 1.0

(to 1.5) Hz.
1a
Number of shock waves, energy setting and repeat treatment sessions

The number of shock waves that can be delivered at each
session depends on the type of lithotripter and shockwave
power.
Starting SWL on a lower enegy setting with step-wise
power (and SWL sequence) ramping prevents renal
injury.
342 Urolithiasis
Clinical experience has shown that repeat sessions are

feasible (within 1 day for ureteral stones).
Procedural control
Results of treatment are operator dependent. Careful imaging
control of localisation will contribute to outcome quality.
Pain control
Careful control of pain during treatment is necessary to limit
pain-induced movements and excessive respiratory excursions.
Antibiotic prophylaxis
No standard prophylaxis prior to SWL is recommended.
Recommendation
LE
In case of infected stones or bacteriuria, antibi- 4

otics should be given prior to SWL.
GR
C
Medical expulsive therapy (MET) after SWL

MET after SWL for ureteral or renal stones can expedite
expulsion and increase stone-free rates, as well as reduce
additional analgesic requirements.
Urolithiasis 343
Percutaneous nephrolitholapaxy (PNL)

Recommendation
GR
Ultrasonic, ballistic and Ho:YAG devices are recomA*

mended for intracorporeal lithotripsy using rigid
nephroscopes.
When using flexible instruments, the Ho:YAG laser is
currently the most effective device available.
Best clinical practice
Contraindications:
all contraindications for general anaesthesia apply;
untreated UTI;
atypical bowel interposition;
tumour in the presumptive access tract area;
potential malignant kidney tumour;
pregnancy.
Pre-operative recommendation - imaging

Preprocedural imaging, including contrast medium
where possible or retrograde study when starting the
procedure, is mandatory to assess stone comprehensiveness, view the anatomy of the collecting system,
and ensure safe access to the kidney stone.
GR
A*
Positioning of the patient: prone or supine?

Traditionally, the patient is positioned prone for PNL,
supine position is also possible, showing advantages in
shorter operating time, the possibility of simultaneous ret344 Urolithiasis
rograde transurethral manipulation, and easier anaesthesia.

Disadvantages are limited manoeuvrability of instruments
and the need of appropriate equipment.
Nephrostomy and stents after PNL
Recommendation
LE
In uncomplicated cases, tubeless (without

1b
nephrostomy tube) or totally tubeless (without
nephrostomy tube and without ureteral stent)
PNL procedures provide a safe alternative.
GR
A
Ureterorenoscopy (URS)
(including retrograde access to renal collecting system)
Best clinical practice in URS
Before the procedure, the following information should be
sought and actions taken (LE: 4):
Patient history;
physical examination (i.e. to detect anatomical and congenital abnormalities);
thrombocyte aggregation inhibitors/anticoagulation
(anti-platelet drugs) treatment should be discontinued.
However, URS can be performed in patients with bleeding
disorders, with only a moderate increase in complications;
imaging.
Recommendation
GR
Short-term antibiotic prophylaxis should be administered.
A*
Urolithiasis 345
Contraindications
Apart from general considerations, e.g. with general anaesthesia, URS can be performed in all patients without any specific contraindications.
Access to the upper urinary tract
Most interventions are performed under general anaesthesia,
although local or spinal anaesthesia are possible. Intravenous
sedation is possible for distal stones, especially in women.
Antegrade URS is an option for large, impacted proximal
ureteral calculi.
Safety aspects
Fluoroscopic equipment must be available in the operating
room. If ureteral access is not possible, the insertion of a JJ
stent followed by URS after a delay of 7-14 days offers an
appropriate alternative to dilatation.
Recommendation
Placement of a safety wire is recommended.
GR
A*
Ureteral access sheaths

Hydrophilic-coated ureteral access sheaths (UAS), can be
inserted via a guide wire, with the tip placed in the proximal
ureter. Ureteral access sheaths allow easy multiple access to
the upper urinary tract and therefore significantly facilitate
URS. The use of UAS improves vision by establishing a continuous outflow, decrease intrarenal pressure and potentially
reduce operating time.
346 Urolithiasis
Stone extraction
The aim of endourological intervention is complete stone
removal (especially in ureteric stones). Smash and go strategies might have a higher risk of stone regrowth and postoperative complications.
Recommendation
LE
Stone extraction using a basket without endo- 4

scopic visualisation of the stone (blind basketing) should not be performed.
Nitinol baskets preserve the tip deflection of
3
flexible ureterorenoscopes, and the tipless
design reduces the risk of mucosa injury.
Nitinol baskets are most suitable for use in
flexible URS.
Ho:YAG laser lithotripsy is the preferred method when carrying out (flexible) URS.
GR
A*
Stenting before and after URS

Pre-stenting facilitates ureteroscopic management of stones,
improves the stone-free rate, and reduces complications.
Following URS, stents should be inserted in patients who are
at increased risk of complications.
Recommendation
LE
Stenting is optional before and after uncompli- 1a

cated URS.
GR
A
Urolithiasis 347
Open surgery
Most stones should be approached primarily with PNL, URS,
SWL, or a combination of these techniques. Open surgery
may be a valid primary treatment option in selected cases.
Indications for open surgery:
Complex stone burden
Treatment failure of SWL and/or PNL, or URS
Intrarenal anatomical abnormalities: infundibular stenosis, stone in the calyceal diverticulum (particularly in an
anterior calyx), obstruction of the ureteropelvic junction,
stricture if endourologic procedures have failed or are not
promising
Morbid obesity
Skeletal deformity, contractures and fixed deformities of
hips and legs
Comorbidity
Concomitant open surgery
Non-functioning lower pole (partial nephrectomy), nonfunctioning kidney (nephrectomy)
Patient choice following failed minimally invasive procedures; the patient may prefer a single procedure and avoid
the risk of needing more than one PNL procedure
Stone in an ectopic kidney where percutaneous access and
SWL may be difficult or impossible
For the paediatric population, the same considerations
apply as for adults.
Laparoscopic surgery
Laparoscopic urological surgery is increasingly replacing
open surgery.
348 Urolithiasis
Indications for laparoscopic kidney-stone surgery include:

complex stone burden;
failed previous SWL and/or endourological procedures;
anatomical abnormalities;
morbid obesity;
nephrectomy in case of non-functioning kidney.
Indications for laparoscopic ureteral stone surgery include:
large, impacted stones;
multiple ureteral stones;
in cases of concurrent conditions requiring surgery;
when other non-invasive or low-invasive procedures have
failed.
If indicated, for upper ureteral calculi, laparoscopic urolithomy has the highest stone-free rate compared to URS and
SWL (LE: 1a).
Laparoscopic ureterolithotomy should be considered when
other non-invasive or low-invasive procedures have failed.
Urolithiasis 349
Recommendations
LE
Laparoscopic or open surgical stone removal

3
may be considered in rare cases where SWL,
URS, and percutaneous URS fail or are unlikely
to be successful.
When expertise is available, laparoscopic sur- 3
gery should be the preferred option before proceeding to open surgery. An exception is complex renal stone burden and/or stone location.
For Ureterolithotomy, laparoscopy is recom2
mended for large impact stones or when endoscopic lithotripsy or SWL have failed.
GR
C
Indication for active stone removal and selection of

procedure
Ureter:
stones with a low likelihood of spontaneous passage;
persistent pain despite adequate pain medication;
persistent obstruction;
renal insufficiency (renal failure, bilateral obstruction, single kidney).
Kidney:
stone growth;
stones in high-risk patients for stone formation;
obstruction caused by stones;
infection;
symptomatic stones (e.g. pain, haematuria);
stones > 15 mm;
stones < 15 mm if observation is not the option of choice;
patient preference (medical and social situation);
> 2-3 years persistent stones.
350 Urolithiasis
The suspected stone composition might influence the choice

of treatment modality.
Recommendations
GR
For asymptomatic caliceal stones in general, active

C
surveillance with an annual follow-up of symptoms and stone status (KUB, ultrasonography [US],
NCCT) is an option for 23 years, whereas intervention should be considered after this period provided
patients are adequately informed.
Observation might be associated with a greater risk of
necessitating more invasive procedures.
STONE REMOVAL
Recommendations
GR
Urine culture or urinary microscopy is mandatory

A*
before any treatment is planned.
Urinary infection should be treated when stone
A
removal is planned.
Anticoagulation therapy including salicylates should B
be stopped before stone removal, in particular if SWL
is planned.
If intervention for stone removal is essential and salicylate therapy should not be interrupted, retrograde
URS is the preferred treatment of choice.
*Upgraded based on panel consensus.
Radiolucent uric acid stones, but not sodium urate or
ammonium urate stones, can be dissolved by oral chemolysis.
Determination is done by urinary pH.
Urolithiasis 351
Recommendation
GR
Careful monitoring of radiolucent stones during/after A

therapy is imperative.
Selection of procedure for active removal of renal stones

Figure 1: Treatment algorithm for renal calculi within the
renal pelvis or upper and middle calices
Kidney stone in renal pelvis or
upper/middle calyx
> 2 cm
1. Endourology (PNL, flex. URS*)

2. SWL
3. Laparoscopy
1-2 cm
SWL or Endourology*,**
< 1 cm
1. SWL
2. Flex. URS
3. PNL
* Flexible URS is used less as first-line therapy for renal stones

> 1.5 cm.
** The ranking of the recommendations reflects a panel
majority vote.
*** see Table 19 extended document
352 Urolithiasis
Figure 2: Treatment algorithm for renal calculi in the inferior calyx

Kidney stone in lower pole
1. Endourology (PNL, flex. URS*)

2. SWL
> 2 cm
Yes
1-2 cm
Favourable
factors for
SWL***
No
< 1 cm
SWL or
Endourology*,**
1. Endourology
2. SWL
1. SWL
2. Flex. URS
3. PNL
Selection of procedure for active stone removal of ureteral stones (GR: A*)
First choice
Second choice
Proximal ureter < 10 mm SWL
URS
Proximal ureter > 10 mm URS (retrograde or antegrade)
or SWL
Distal ureter < 10 mm
URS or SWL
Distal ureter > 10 mm
URS
SWL
Urolithiasis 353
Recommendation
GR
Percutaneous antegrade removal of ureteral stones

is an alternative when SWL is not indicated or has
failed, and when the upper urinary tract is not amenable to retrograde URS.
Patients should be informed that URS is associated
with a better chance of achieving stone-free status
with a single procedure, but has higher complication
rates.
Steinstrasse
Steinstrasse occurs in 4% to 7% of cases after SWL, the major
factor in steinstrasse formation is stone size.
Recommendations
LE
GR
Medical expulsion therapy increases the stone

expulsion rate of steinstrasse.
PCN is indicated for steinstrasse associated
with UTI/fever.
SWL is indicated for steinstrasse when large
stone fragments are present.
Ureteroscopy is indicated for symptomatic
steinstrasse and treatment failure.
1b
354 Urolithiasis
Residual stones
Recommendations
LE
GR
Identification of biochemical risk factors and

appropriate stone prevention is particularly
indicated in patients with residual fragments
or stones.
Patients with residual fragments or stones
should be followed up regularly to monitor
disease course.
After SWL and URS, MET is recommended
using an alpha-blocker to improve fragment
clearance and reduce the probability of residual
stones.
For well-disintegrated stone material residing
in the lower calix, inversion therapy during
high diuresis and mechanical percussion facilitate stone clearance.
1b
1a
1a
The indication for active stone removal and selection of the

procedure is based on the same criteria as for primary stone
treatment and also includes repeat SWL.
Management of urinary stones and related problems

during pregnancy
Recommendations (GR: A*)
US is the method of choice for practical and safe evaluation
of pregnant women.
In symptomatic patients with suspicion of ureteral stones
during pregnancy, limited IVU, MRU, or isotope renography is a possible diagnostic method.
Urolithiasis 355
Following correct diagnosis, conservative management

should be the first-line treatment for all non-complicated
cases of urolithiasis in pregnancy (except those that have
clinical indications for intervention).
If intervention becomes necessary, placement of an internal stent, percutaneous nephrostomy, or ureteroscopy are
treatment options.
Regular follow-up until final stone removal is necessary
due to higher encrustation of stents during pregnancy.
Management of stone problems in children

Spontaneous passage of a stone and of fragments after SWL is
more likely to occur in children than in adults (LE: 4). For
paediatric patients, the indications for SWL and PNL are
similar to those in adults, however they pass fragments more
easily. Children with renal stones with a diameter up to 20
mm (~300 mm2) are ideal candidates for SWL.
Recommendation
Ultrasound evaluation is the first choice for imaging
in children and should include the kidney, the filled
bladder and adjoining portions of the ureter.
*Upgraded from B following panel consensus.
356 Urolithiasis
GR
A*
Stones in exceptional situations

Caliceal diverticulum stones SWL, PNL (if possible) or
RIRS (retrograde intrarenal
surgery via flexible ureteroscopy).
Can also be removed using
laparoscopic retroperitoneal
surgery.
Patients may become asymptomatic due to stone disintegration (SWL) whilst welldisintegrated stone material
remains in the original position due to narrow caliceal
neck.
Horseshoe kidneys
Can be treated in line with
the stone treatment options
described above.
Passage of fragments after
SWL might be poor.
Stones in pelvic kidneys
SWL, RIRS or laparoscopic
surgery
For obese patients, the
options are SWL, PNL, RIRS
or open surgery
Urolithiasis 357
Patients with obstruction of

the ureteropelvic junction
When the outflow abnormality has to be corrected,

stones can be removed
with either percutaneous
endopyelotomy or open
reconstructive surgery.
URS together endopyelothomy with Ho:YAG.
Incision with an Acucise balloon catheter might be considered, provided the stones
can be prevented from falling into the pelvo-ureteral
incision.
Stones in transplanted kidUse of PNL is recommended,
neys
however SWL or (flexible)
ureteroscopy are valuable
alternatives.
Stones formed in urinary
Individual management necdivision
essary.
For smaller stones SWL is
effective.
PNL and antegrade flexible
URS are frequently used
endourological procedures.
Stones formed in a continent Present a varied and often
reservoir
difficult problem.
Each stone problem must be
considered and treated individually.
358 Urolithiasis
Stones in patients with neurogenic bladder disorder
For stone removal all methods apply based on individual situation.

Careful patient follow-up
and effective precentive
strategies are important.
General considerations for recurrence prevention (all

stone patients)
Drinking advice (2.5 3L/day, neutral pH);
Balanced diet;
Lifestyle advice.
High-risk patients: stone-specific metabolic work-up and

pharmacological recurrence prevention
Pharmacological stone prevention is based on a reliable
stone analysis and the laboratory analysis of blood and urine
including two consecutive 24-hour urine samples.
Pharmacological treatment of calcium oxalate stones

(Hyperparathyreoidism excluded by blood examination)
Risk factor
Hypercalciuria
Hyperoxaluria
Hypocitraturia
Enteric hyperoxaluria
Suggested treatment
Thiazide + potassium
citrate
Oxalate restriction
Potassium citrate
Potassium citrate
Calcium supplement
Oxalate absorption
LE
1a
GR
A
2b
1b
3-4
2
3
A
A
C
B
B
Urolithiasis 359
Small urine volume

Increased fluid intake
Distal renal tubular
Potassium citrate
acidosis
Primary hyperoxaluria Pyridoxine
1b
2b
A
B
Pharmacological treatment of calcium phosphate stones

Risk factor
Rationale
Hypercalciuria Calcium
excretion
> 8 mmol/day
pH constantly
Inadequate
> 6.2
urine pH
Urinary tract
infection
Eradication of
urea-splitting
bacteria
Medication
Hydrochlorothiazide, initially 25 mg/day, increasing up to 50 mg/day
L-Methionine, 200-500
mg 3 times daily, with
the aim of reducing urine
pH to 5.8-6.2
Antibiotics
Hyperparathyroidism
Elevated levels of ionized calcium in serum (or total calcium
and albumin) require assessment of intact parathyroid hormone (PTH) to confirm or exclude suspected hyperparathyroidism (HPT). Primary HTP can only be cured by surgery.
360 Urolithiasis
Pharmacological treatment of uric acid and ammonium

urate stones
Risk factor
Rationale for
pharmacological
therapy
Inadequate urine Urine pH constantly < 6.0;
pH
acidic arrest in
uric acid stones
Hyperuricosuria
Medication
Alkaline citrate OR
Sodium bicarbonate
Prevention: targeted
urine pH 6.2-6.8
Chemolitholysis:
targeted urine pH
7.0-7.2
Adequate antibiotUrine pH constantly > 6.5 in
ics in case of UTI
ammonium urate L-Methionine,
200-500 mg 3 times
stones
daily; targeted urine
pH 5.8-6.2
Uric acid excretion Allopurinol,
> 4.0 mmol/day
100 mg/day (LE: 3;
GR: B)
Hyperuricosuria
Allopurinol,
and hyperuricemia 100-300 mg/day,
> 380 mol
depending on kidney function
Urolithiasis 361
Struvite and infection stones

Therapeutic measure recommendations
Surgical removal of the stone material as completely as possible
Short-term antibiotic course
Long-term antibiotic course
Urinary acidification: ammonium chloride;
1 g, 2 - 3 x daily
Urinary acidification: methionine;
200-500 mg, 1 - 3 x daily
Urease inhibition
LE
GR
3
3
3
B
B
B
1b
Pharmacological treatment of cystine stones

Risk factor
Cystinuria
Inadequate
urine pH
362 Urolithiasis
Rationale for
pharmacological
therapy
Cystine excretion
> 3.0-3.5 mmol/day
Improvement of cystine solubility Urine

pH optimum 7.5-8.5
Medication
Tiopronin, 250 mg/

day initially, up to a
maximum dose of
2 g/day
NB: TACHYPHYLAXIS IS POSSIBLE
(LE: 3; GR: B)
Alkaline Citrate or
Sodium Bicarbonate
Dosage is according
to urine pH (LE: 3,
GR: B)
2,8-dihydroyadenine stones and xanthine stones

Both stone types are rare. In principle, diagnosis and specific
prevention is similar to that of uric acid stones.
Investigating a patient with stones of unknown composition

Investigation
Medical history
Diagnostic
imaging
Blood analysis
Urinalysis
Rationale for investigation

- Stone history (former stone events, family history)
- Dietary habits
- Medication chart
- Ultrasound in case of a suspected stone
- NCCT
(Determination of the Houndsfield unit
provides information about the possible
stone composition)
- Creatinine
- Calcium (ionized calcium or total calcium + albumin)
- Uric acid
- Urine pH profile (measurement after
each voiding, minimum 4 times a day)
- Dipstick test: leucocytes, erythrocytes,
nitrite, protein, urine pH, specific
weight
- Urine culture
- Microscopy of urinary sediment
(morning urine)
Urolithiasis 363
This short booklet text is based on the more comprehensive EAU guidelines (ISBN 978-90-79754-83-0) available to all members of the European
364 Urolithiasis
GUIDELINES ON
RENAL TRANSPLANTATION
G. Karam (chairman), T. Klble, A. Alcaraz, F.T. Aki,

K. Budde, U. Humke, F. Kleinclauss, G. Nicita,
J.O. Olsburgh, C. Ssal
Introduction
As attitudes and practice to renal transplantation (RT) vary
significantly, the Guidelines provide general guidance only.
Kidney donation
There is a widening gap between donation and demand for
kidney transplants, with not enough deceased donors. There
is, however, a clear trend towards an increase in living-donor
transplants.
Recommendations for increasing donation
GR
Deceased donors
C
In all countries without presumed consent law,
increase efforts to recruit donors through an opting-in
register or by carrying donor cards.
B
Greater use of non-heart-beating donors (NHBD)
should be made. Create policies for recently dead
admissions to casualty departments which may be
used as NHBDs.
Renal Transplantation 365
Use of carefully selected donors > 60 years should be

encouraged as a continuing source of deceased-donor
kidneys.
Organs from deceased donors > 70 years should be
individually evaluated.
Living donors
Organ donation should be considered a charitable gift.
Society can express gratitude to organ donors for their
gift (e.g. Medal of Honour, donor insurance).
Explore living donation when a patient first presents
with end-stage renal disease.
Decisions about multiple renal artery or grafts with
anatomical anomalies should be made on an individual basis.
Laparoscopic nephrectomy offers similar results
(complications, graft function and graft survival) compared to open nephrectomy, with less post-operative
morbidity, shorter convalescence and better cosmetic
results.
Laparoscopic nephrectomy increases the number of
people wainting to donate.
Paired kidney exchange, if permitted by national law,
laparoscopy is a way of increasing the number of kidney transplants.
C
C
C
C
Kidney donor selection and refusal criteria

The physical condition of the donor, especially of the organ
to be donated, is more important than age. Important risk
factors for organ failure are a prolonged history of diabetes
mellitus or serious hypertension with retinal vascular damage. Factors for excluding potential donors or for considering
366 Renal Transplantation
single- rather than multi-organ donations include previous

myocardial infarction, coronary bypass angina, severe systemic vascular disease and long-lasting hypotension, oliguria,
and a long period in intensive care.
The potential donor should be assessed for human immunodeficiency virus-1, -2 (HIV-1, HIV-2), hepatitis C virus
(HCV) and hepatitis B surface antigen (HBsAg), anti-hepatitis
B core (anti-HBc) antibody, acute hepatitis (liver enzymes),
cytomegalovirus (CMV), Epstein-Barr virus if the recipient is
paediatric, active syphilis, other viral infections, sepsis, tuberculosis, infections of unknown aetiology, and a family history
(or possible clinical signs) of Creutzfeldt-Jacob disease.
Different circumstances apply when a recipient is already
infected with HIV or hepatitis and transplant from infectious
donors is possible in certain situations.
A previous history of malignancy need not be a contraindication for organ donation. However, absolute contraindications
are active cancer or a history of metastatic cancer (with a
few exceptions, e.g. testicular cancer) and cancers with high
recurrence rates, e.g. lymphoma. Exclude metastasis as a
cause of intracranial bleeding in a potential donor with a
brain haemorrhage of unknown aetiology. For special exceptions in malignancy, consult the full Guidelines.
Kidneys from marginal donors must have a calculated creatinine clearance rate (CrCl) of 50-60 mL/min. Kidneys with
CrCl < 50 mL/min are only suitable for dual transplant.
Recommendations for brain dead donors
GR
Consider every brain-dead comatose subject as a
potential organ donor, without age limits.
Obtain agreement for organ harvesting from relatives
(significant others) according to local law and policies. Authorisation for explantation by the donors
close relatives is always recommended, even if local
legislation presumes consent.
Always exclude individuals who objected to donation C
during life.
A donor organ affected by a potentially transmissible B
pathology (infections, neoplasias) must be carefully
evaluated considering the risk/benefits for the
recipient.
A good-quality organ must be guaranteed to the recip- C
ient and every transplant centre must establish its own
guidelines on organ acceptability. Marginal organs
can only be used after thorough assessment. Counsel
recipients and confirm their acceptance.
Surgical techniques
GR
Living-donor transplantation is associated with higher B
success rates than deceased-donor transplantation.
The surgeon is responsible for making sure the donor B
is medically and psychologically suitable, the donated
organ is healthy, and success in the recipient is likely.
B
Always leave the donor with the better kidney. The
transperitoneal approach carries a higher risk of
splenic and intestinal complications.
Open-donor nephrectomy should be performed by an

extraperitoneal approach through a subcostal or dorsal lumbotomy incision.
Laparoscopic donor nephrectomy (either trans- or
retro-peritoneal) should only be performed by those
trained in the procedure.
Hand-assisted laparoscopic donor nephrectomy
minimises warm ischaemia time compared to classic
laparoscopic procedures.
Kidney recipient
Careful pre-operative work-up of all transplant candidates is
mandatory to improve organ and patient survival in the posttransplant period. The work-up should be repeated regularly.
Recommendations for pre-transplant therapy

In the abnormal urogenital tract, meticulous pretransplant work up is necessary, with urodynamics
being the key investigation.
If pharmacological therapy or intermittent catheterisation fails or is impossible, urinary diversion is
necessary using catheterisable pouches, conduits, or
cystoplasties.
Remove kidneys with autosomal-dominant polycystic
kidney disease if there is insufficient space or complications (chronically infected kidneys, or kidneys with
suspected tumour growth).
GR
B/C
B/C
B/C
Other special considerations in a recipient
Recommendations
Active malignancy is a contraindication because
immunosuppression may aggravate underlying malignancy jeopardising the patients life and graft outcome.
The waiting period before transplantation in recipients
with a history of malignancy depends on the type,
TNM stage and grade of the tumour, age, and general
health.
Active infection may exacerbate after transplantation
and may be life-threatening.
Screen for viral and bacterial diseases in all transplant
candidates including hepatitis B (HBV), hepatitis C
(HCV), human immunodeficiency virus (HIV),
cytomegalovirus (CMV), and tuberculosis (TB).
Routine screening examination of all patients in all
subspecialties is not necessary. However, a patient
with history and symptoms suspicious for an underlying active infection should be seen by the appropriate
specialist (e.g. ear, nose, and throat specialist; dentist;
dermatologist; urologist and/or gynaecologist) to
firmly rule out infectious foci.
Re-evaluation of non-compliance (and serious morbidity) may be appropriate.
GR
B
The pre-transplant work-up should focus on looking

for cardiac disease. The work-up should be extensive
in patients at high risk of cardiac disease to firmly rule
out coronary artery disease. Perform any revascularisation before transplantation.
Peripheral artery disease is common in uraemic
patients. Special attention should be paid to iliacal,
peripheral, and cerebrovascular disease using appropriate diagnostic and therapeutic measures.
Patients with diabetes mellitus should be transplanted.
They require an extensive pre-transplant work-up.
Obesity itself is not a contraindication for transplantation. A thorough pre-transplant evaluation and
attempt to reduce weight are recommended.
Patients at risk of coagulopathies should be carefully
evaluated to prevent early post-transplant thrombotic
events.
Diseases that might influence post-transplant course
(e.g. diverticulosis, cholecystolithiasis, hyperparathyroidism) should be identified during pre-transplant
work-up and if possible treated before transplantation.
Age itself is not a contraindication, but the recipient
must undergo a thorough pre-transplant evaluation
and risk-benefit assessment and be counselled about
the increased risks associated with age.
B
C
C
Recurrence of the original renal disease is common,
though graft loss due to recurrence is not. Only a few
rare diseases with a high recurrence rate leading to
early graft loss are contraindications for transplantation. Patients at risk of recurrent disease should be
counselled especially before living related-donor transplantation.
Matching of donors and recipients

Recommendations
GR
Determine ABO blood group and HLA-A, -B, and -DR B
phenotypes of all candidates awaiting transplantation.
To avoid hyper-acute rejection (HAR), cross-matching B
must be performed before transplantation.
Kidneys from deceased donors should be allocated to recipients with the lowest number of HLA mismatches. Falsepositive results for cross-matching may occur especially in
autoimmune diseases. Potential recipients with a high percentage of panel-reactive antibodies (%PRA) can be further
analysed to ensure a negative cross-match. ABO blood group
matching prevents HAR, but technical advances have resulted in successful ABO-incompatible transplantation.
Immunosuppression after kidney transplantation

The current standard initial immunosuppression provides
excellent efficacy with good tolerability: calcineurin inhibitor
(CNI; cyclosporine or tacrolimus) + mycophenolate (mycophenolate mofetil [MMF] or enteric-coated mycophenolate
sodium [EC-MPS]) + corticosteroid (prednisolone or methylprednisolone). Induction therapy may also be given.
Recommendations for immunosuppressive therapy GR

Rejection prophylaxis using CNIs remains current
best practice.
Choice of CNI (cyclosporine or tacrolimus) depends
on immunological risk, recipient characteristics, concomitant immunosuppression, and socio-economic
factors.
Blood-level monitoring of both cyclosporine and tacrolimus is mandatory to prevent under-immunosuppression (increased risk of rejection) and excessively
high blood levels (increased risk of chronic sideeffects, particularly nephrotoxicity).
Mycophenolates are the current standard of care. The
standard dose of MMF combined with cyclosporine is
1 g twice daily or EC-MPS 720 mg twice daily.
Combination therapy of Mycophenolates with tacrolimus is not formally approved. Optimal mycophenolate (MPA) dosing is unclear, as tacrolimustreated patients have a higher MPA exposure than
cyclosporine-treated patients. The standard starting
dose of MMF combined with tacrolimus is MMF 1 g
twice daily or EC-MPS 720 mg twice daily. This dosage is often dose-reduced with 30-50% lower doses at
1 year.
MPA monitoring cannot be recommended for all
patients due to limited evidence of benefit.
Azathioprine may be used in a low-risk population
for initial immunosuppression, especially in patients
intolerant to MPA formulations.
A
A
A
A
Initial steroid therapy remains the standard of care in

perioperative and early postoperative period.
In order to reduce steroid associated side effects,
steroids may be stopped in most patients after 3-12
months on combination therapy with CNI and MPA.
A
A
Recommendations for other immunosuppressive

therapies
mTOR inhibitors (sirolimus, everolimus)
Acute rejection can be effectively prevented by inhibitors of the mammalian target of rapamycin (mTOR)
(sirolimus, everolimus) combined with CNIs. Reduce
CNI dosage to avoid aggravated nephrotoxicity.
Initial CNI-free combination therapy of mTOR inhibitors with MPA and steroids is not sufficient to prevent
acute rejection compared to a standard regimen.
Prophylactic surgical measures must be used when
mTOR inhibitors are given in the perioperative period
because of impaired wound healing.
mTOR inhibitors are an alternative to CNIs if there
are severe CNI-related side-effects.
Blood levels of sirolimus and everolimus must be
regularly monitored.
T-cell depleting induction therapy
Potential life-threatening side-effects include a higher
incidence of severe opportunistic infections and
malignancy, particularly post-transplant lymphoproliferative disease.
T-cell depleting therapy has not resulted in improved
outcomes overall.
GR
A
A
A
T-cell depleting therapy should not be routinely used B

in a low-risk first-transplant recipient.
Patients must be informed of the increased risks of
B
infection and cancer.
Interleukin-2 receptor antibodies (IL-2R)
They reduce the rate of acute rejection, enabling CNI- A
and steroid-sparing regimens.
Complications
Hyper-acute rejection (HAR) is rare and usually occurs within minutes or hours of vascularisation, although it may occur
up to 1 week post transplant. It is cured by graft removal.
Acute allograft rejection can be classified into acute cellular
rejection (ACR, T-cell mediated) or acute humoral rejection
(AHR, antibody-mediated). Test patients with ACR immediately for HLA IgG antibodies reactive with the graft. Steroid
bolus therapy is recommended as initial treatment. In severe,
or steroid-resistant, rejection, consider intensified immunosuppression, including high-dose steroid treatment, conversion to tacrolimus, and T-cell depleting agents. Treatment of
AHR may include steroid bolus therapy, conversion to tacrolimus, antibody elimination and intravenous immunoglobulin treatment. Anti-CD20 (rituximab) or T-cell depleting
agents may be efficacious.
Chronic allograft dysfunction may take months or years to
develop. Perform a renal biopsy and determine donor-specific
alloantibodies if changes develop during follow-up monitoring of serum creatinine, creatinine clearance, blood pressure,
blood lipids, and urinary protein excretion. If IF/TA is conRenal Transplantation 375
firmed, begin appropriate medical treatment, e.g. control of

hypertension. Consider conversion to an mTOR inhibitor in
patients under current CNI therapy and/or with histological
signs suggesting CNI toxicity without significant proteinuria
(< 800 mg/day). Alternatives are substantial CNI reduction
under MPA protection or, in chronic maintenance patients,
CNI withdrawal under MPA and steroids.
Post-transplantation cancer is a common long-term cause of
death. Most malignancy affects the skin (40%) or lymphatic
system (11%). Closely monitor young recipients and patients
who have received T-cell depleting agents. Annual screening
for cancer and co-morbidity is mandatory.
Annual screening
Lifelong regular post-transplant follow-up by an experienced
and trained transplant specialist is strongly recommended at
least every 6-12 months. Monitoring of renal function and
immunosuppression and side-effects by a physician, every
4-8 weeks is strongly advised.
GUIDELINES ON
PAEDIATRIC UROLOGY
(Limited text update February 2012)
S. Tekgl (co-chairman), H. Riedmiller (co-chairman),

H.S. Dogan, P. Hoebeke, R. Kocvara, J.M. Nijman (vice-chairman), Chr. Radmayr, R. Stein
Introduction
Due to the scope of the extended Guidelines on Paediatric
Urology, no attempt has been made to include all topics, but
rather to provide a selection based on practical considerations.
PHIMOSIS
Background
At the end of the first year of life, retraction of the foreskin
behind the glanular sulcus is possible in only about 50% of
boys. The phimosis is either primary (physiological) with no
sign of scarring, or secondary (pathological), resulting from
scarring due to conditions such as balanitis xerotica obliterans.
Phimosis must be distinguished from normal agglutination of
the foreskin to the glans, which is a physiological phenomenon. If the tip remains narrow and glanular adhesions were
separated, then the space is filled with urine during voiding,
causing the foreskin to balloon outward.
Paediatric Urology 377
Treatment
Treatment of phimosis in children is dependent on the
parents preferences, and can be plastic or radical circumcision after completion of the second year of life. Plastic circumcision (dorsal incision, partial circumcision) carries the
potential for recurrence of the phimosis. Associated frenulum
breve is corrected by frenulotomy. Meatoplasty is added if
necessary. Childhood circumcision should not be recommended without a medical reason.
Circumcision: indication and contraindication
An absolute indication for circumcision is secondary phimosis. The indications for early surgery in primary phimosis are
recurrent balanoposthitis, and recurrent urinary tract infections in patients with urinary tract abnormalities. Routine
neonatal circumcision to prevent penile carcinoma is not
indicated.
Contraindications for circumcision are coagulopathy, an
acute local infection and congenital anomalies of the penis,
particularly hypospadias or buried penis, because the foreskin may be required for a reconstructive procedure.
As a conservative treatment option of the primary phimosis,
a corticoid ointment or cream (0.05-0.10%) can be administered twice a day over a period of 20-30 days. This treatment
has no side-effects. Agglutination of the foreskin does not
respond to steroid treatment.
378 Paediatric Urology
Paraphimosis
Paraphimosis must be regarded as an emergency situation.
It is characterised by retracted foreskin with the constrictive
ring localised at the level of the sulcus. Treatment of paraphimosis consists of manual compression of the oedematous
tissue with a subsequent attempt to retract the tightened
foreskin over the glans penis. A dorsal incision of the constrictive ring may be required, or circumcision is carried out
immediately or in a second session.
CRYPTORCHIDISM
Cryptorchidism is a very common congenital anomaly affecting nearly 1% of full-term male infants. Clinical management
is determined by classification into palpable and non-palpable testes. Retractile testes have completed their descent,
but may be retained in the groin by a strong cremasteric
reflex, and require only observation. Bilateral, non-palpable
testes with any suggestion of sexual differentiation problems
require urgent endocrinological and genetic evaluation
(LE: 3; GR: B).
Physical examination is the only method of differentiating
palpable and non-palpable testes. There is no benefit from
ultrasound (US), computed tomography (CT), magnetic
resonance imaging (MRI) or angiography. Diagnostic laparoscopy is the only reliable examination to confirm or exclude
an intra-abdominal, inguinal and absent/vanishing testis
(non-palpable testis) (LE: 1b; GR: A). Before trying laparoscopy, examination under general anaesthesia should be
carried out because some, originally non-palpable, testes are
palpable under anaesthesia.
Treatment
Medical therapy
To prevent histological deterioration, medical or surgical
treatment should be carried out and finished before 12-18
months of age. Medical therapy (human chorionic gonadotrophin or gonadotrophin-releasing hormone) is not recommended for descending the testis as it may produce testicular
descent in only up to 20% of cases. There is some evidence
that this may improve future fertility; yet there is no long
term data.
Surgery
Surgery differs for palpable or non-palpable testes.
Orchidopexy (inguinal approach) is used for palpable testis
(up to 92% success). Inguinal surgical exploration should be
attempted for non-palpable testes and the abdomen should
be searched laparoscopically, if, rarely, there are no vessels or
vas deferens in the groin. Laparoscopy can be used for testis
removal or orchidolysis and orchiopexy.
Remove an intra-abdominal testis in a boy > 10 years with
a normal contralateral testis. A one-stage or two-stage
Fowler-Stephens procedure can be performed in a bilateral
intra-abdominal testes or in a boy < 10 years. Microvascular
auto-transplantation has a 90% testicular survival rate, but
requires very skilful and experienced surgical techniques.
Prognosis
Boys with one undescended testis have a lower fertility rate,
but the same paternity rate as boys with bilateral descended
testes. Boys with an undescended testis are 20 times more
likely to develop testicular malignancy, independent of treatment choice. Early orchiopexy may reduce the risk of testicular cancer and surgical orchidolysis and orchidopexy should
therefore be performed by 12-18 months of age.
HYDROCELE
Background
Incomplete obliteration of the processus vaginalis peritonei
results in formation of various types of communicating
hydrocele, alone or connected with other intrascrotal
pathology (hernia).
Non-communicating hydroceles are found secondary to minor
trauma, testicular torsion, epididymitis, or varicocele operation, or may appear as a recurrence after primary repair of a
communicating hydrocele.
A communicating hydrocele vacillates in size, usually relative
to activity. It is diagnosed by medical history and physical
investigation, the swelling is translucent, and transillumination of the scrotum makes the diagnosis. If there are any
doubts about the intrascrotal mass, ultrasound should be performed. Contralateral disease should be excluded.
Treatment (Surgery)
Surgical treatment of hydrocele is not indicated within the
first 12-24 months because of the tendency for spontaneous
resolution.
Early surgery is indicated if there is suspicion of a concomitant inguinal hernia or underlying testicular pathology.
There is no evidence that this type of hydrocele risks
testicular damage.
In the paediatric age group, the operation consists of ligation of the patent processus vaginalis via an inguinal incision, leaving the distal stump open, whereas in hydrocele of
the cord, the cystic mass is excised or unroofed. Sclerosing
agents should not be used because of the risk of chemical
peritonitis in the communicating processus vaginalis peritonei.
The scrotal approach (Lord or Jaboulay technique) is used in
the treatment of a secondary non-communicating hydrocele.
HYPOSPADIAS
Background
Hypospadias are usually classified according to the anatomical location of the proximally displaced urethral orifice:
distal - anterior hypospadias (glanular, coronal or distal
penile);
intermediate - middle (penile);
proximal - posterior (penoscrotal, scrotal, perineal).
The pathology may be much more severe after skin release.
Assessment
Patients with hypospadias should be diagnosed at birth. The
diagnostic evaluation also includes an assessment of associated anomalies, which are cryptorchidism and open processus
vaginalis or inguinal hernia. Severe hypospadias with unilaterally or bilaterally impalpable testis, or with ambiguous
genitalia, require a complete genetic and endocrine work-up
immediately after birth to exclude intersexuality, especially
congenital adrenal hyperplasia.
Trickling urine and ballooning of the urethra require exclusion of meatal stenosis.
The length of the hypospadiac penis may be distorted by
penile curvature, by penoscrotal transposition, or may be
smaller due to hypogonadism.
Differentiation between functionally necessary and aesthetically feasible operative procedures is important for therapeutic decision-making. As all surgical procedures carry the risk
of complications, thorough pre-operative counselling of the
parents is crucial. The therapeutic objectives are to correct
the penile curvature, to form a neo-urethra of an adequate
size, to bring the neomeatus to the tip of the glans, if possible, and to achieve an overall acceptable cosmetic appearance. This goal is achieved by using different surgical techniques according to the individual findings.
Surgery
The age at surgery for primary hypospadias repair is usually
6-18 months. For repeat hypospadias repairs, no definitive
guidelines can be given.
Outcome
Excellent long-term functional and cosmetic results can be
achieved after repair of anterior penile hypospadias. The
complication rate in proximal hypospadias repair is higher.
Figure 1 gives an algorithm for the management of hypospadias.
Figure 1: Algorithm for the management of hypospadias

Hypospadias
Diagnosis at birth
Intersex
Paediatric urologist
No reconstruction
Reconstruction required
Preparation
(foreskin, hormone therapy)
Distal
Proximal
Chordee
Urethral
plate
cut
TIP, Mathieu, MAGPI,

King, advancement, etc.
Tube-onlay, inlay-onlay,
Koyanagi, two-stage
procedure
(local skin, bucal
mucosa)
No chordee
Urethral
plate
preserved
Onlay, TIP, two-stage

procedure
(local skin, buccal
mucosa)
TIP = tubularised incised plate; MAGPI = meatal advancement

and glanuloplasty technique.
MICROPENIS
Micropenis is defined as a small but otherwise normally
formed penis with a stretched length of less than 2.5 cm SD
below the mean (Table 1).
Table 1: Length of the penis in boys

(according to Feldmann and Smith)
Age
Newborns
0-5 months
6-12 months
1-2 y
2-3 y
3-4 y
4-5 y
5-6 y
6-7 y
7-8 y
8-9 y
9-10 y
10-11 y
Adults
Mean SD (cm)
3.5 0.4
3.9 0.8
4.3 0.8
4.7 0.8
5.1 0.9
5.5 0.9
5.7 0.9
6.0 0.9
6.1 0.9
6.2 1.0
6.3 1.0
6.3 1.0
6.4 1.1
13.3 1.6
VARICOCELE IN CHILDREN AND ADOLESCENTS

Background
Varicocele is unusual in boys under 10 years of age, but
becomes more frequent at the beginning of puberty. Fertility
problems will arise in about 20% of adolescents with varicocele. The adverse influence of varicocele increases with
time.
Testicular catch-up growth and improvement in sperm

parameters after varicocelectomy has been reported in adolescents.
Varicocele is mostly asymptomatic, rarely causing pain at
this age. It may be noticed by the patient or parents, or discovered by the paediatrician at a routine visit. Diagnosis and
classification depends upon the clinical finding and ultrasound investigation.
Treatment (Surgery)
Surgical intervention is based on ligation or occlusion of the
internal spermatic veins. Microsurgical lymphatic-sparing
repair (microscopic or laparoscopic) are associated with the
lowest recurrence and complication rates. There is no evidence that treatment of varicocele at paediatric age will offer
a better andrological outcome than an operation performed
later.
Follow-up
During adolescence, testicular size should be checked annually. After adolescence, repeated sperm analysis is to be recommended.
Figure 2 shows an algorithm for the diagnosis of varicocele
in children and adolescents, and Figure 3 shows an algorithm
for its treatment.
Figure 2: Algorithm for the diagnosis of varicocele in children and adolescents

Varicocele in children
and adolescents
Physical examination in
the upright position
Grade I - Valsalva positive
Grade II - palpable
Grade III - visible
Ultrasound investigation
Venous reflux detected on
Doppler ultrasound
Size of the testes
Figure 3: Algorithm for the treatment of varicocele in children and adolescents

Varicocele in children
and adolescents
Surgery:
indication
type
Conservative treatment:
indication
follow-up
Small testis (growth arrest)

Additional testicular
pathology
Bilateral palpable
varicocele
Pathological spermiogram
Symptomatic varicocele
Symmetrical testes
Normal spermiogram (in
older adolescents)
Microsurgical lymphaticsparing repair (microscopic

or laparoscopic)
Measurement of testicular
size (during adolescence)
Repeated sperm analysis
(after adolescence)
MONOSYMPTOMATIC NOCTURNAL ENURESIS

Background
Enuresis is incontinence during the night. Any wetting during sleep above the age of five years is enuresis. It is important to note that there is a single symptom only. Due to an
imbalance between night-time urine output and night-time
bladder capacity, the bladder can easily become full at night,
and the child will either wake up to empty the bladder or
will void during sleep.
Assessment
A voiding diary, registering the daytime bladder function and
the night-time urine output will help guide the treatment.
Measuring the daytime bladder capacity gives an estimate of
bladder capacity to compare with normal values for age.
Figure 4 gives an algorithm for the diagnosis and treatment
of monosymptomatic nocturnal enuresis.
Figure 4: Algorithm for the diagnosis and treatment of

monosymptomatic nocturnal enuresis
Nocturnal enuresis
Initial assessment
Monosymptomatic
Nocturnal enuresis
Education
Voiding diary or
direct questioning
Voiding habits
Wetting episodes
Bowel function
Urinalysis
Daytime wetting
Urge syndrome
Lower tract dysfunction
Infection
Other
Supportive therapy
Alarm or desmopressin
still wet
Uroflowmetry, urine V, Osm *
Check for night time polyuria
investigate for sleep disorders
Overactivity of the bladder
Urotherapy, Ab, Ach, **

Biofeedback
Consider longer use of desmopression

Combination therapies
Imipramine
Vesicouretereric reflux (VUR) in children

VUR present within a wide range of severity, and a majority
of reflux patients will not develop renal scars and probably
will not need any intervention. The main goal in management is the preservation of kidney function.
Diagnosis
The diagnostic work-up should evaluate the overall health
and development of the child. A basic diagnostic work-up
includes a detailed medical history (including family history,
and screening for lower urinary tract dysfunction [LUTD]),

physical examination including blood pressure measurement,
urinalysis (assessing proteinuria), urine culture, and serum
creatinine in patients with bilateral renal parenchymal abnormalities.
Infants presenting because of prenatally diagnosed
hydronephrosis
Ultrasound of the kidney and bladder is the first standard evaluation tool for children with prenatally diagnosed
hydronephrosis. It should be delayed to the end of first
week after birth because of early oliguria in the neonate. It is
essential to evaluate the bladder, as well as the kidneys.
Recommendations for the use of VCUG in prenatal

hydronephrosis
US findings of bilateral high-grade hydronephrosis, duplex
kidneys, ureterocele, ureteric dilatation, and abnormal bladders, because the likelihood of VUR is much higher.
In all other conditions, the use of VCUG to detect reflux is
optional.
When cases identified by prenatal US become symptomatic
with UTIs, further evaluation with VCUG should be considered.
Recommendations for paediatric screening of VUR

The parents of children with VUR should be informed that
siblings and offspring have a high prevalence of VUR.
If screening is performed, siblings should be screened by
renal US. VCUG is recommended if there is evidence of
renal scarring on US or a history of UTI.
In older children who are toilet-trained, there is no added

value in screening for VUR.
UTI = urinary tract infecting; VCUG = voiding cystourethrography.
Conservative therapy
The objective of conservative therapy is prevention of febrile
UTI. It is based on the understanding that:
VUR resolves spontaneously, mostly in young patients
with low-grade reflux. However, spontaneous resolution is
low for bilateral high-grade reflux).
VUR does not damage the kidney when patients are free
of infection and have normal lower urinary tract function.
There is no evidence that small scars can cause hypertension, renal insufficiency or problems during pregnancy.
The conservative approach includes watchful waiting,
intermittent or continuous antibiotic prophylaxis, and
bladder rehabilitation in those with LUTD.
Circumcision during early infancy may be considered as
part of the conservative approach, because it is effective in
reducing the risk of infection in normal children.
Surgical treatment
Surgical treatment comprises endoscopic injection of bulking
agents or ureteral reimplantation.
Subureteric infection of bulking agents: due to the availability
of biodegradable substances, endoscopic subureteric injection of bulking agents has become an alternative to long-term
antibiotic prophylaxis and surgical intervention.
Open surgical techniques: Overall, all surgical procedures offer

very high and similar success rates for correcting VUR.
Laparoscopy: a laparoscopic approach cannot be recommended as a routine procedure. It can be offered as an alternative
to the parents in centres where there is enough experience.
Recommendations for the management of VUR in

childhood
Regardless of the grade of reflux or presence of renal scars,
all patients diagnosed within the first year of life should be
treated initially with CAP. During early childhood, the kidneys are at higher risk of developing new scars. Immediate,
parenteral antibiotic treatment should be initiated for
febrile breakthrough infections. Definitive surgical or endoscopic correction is the preferred treatment in patients with
frequent breakthrough infections.
Surgical correction should be considered in patients with
persistent high-grade reflux (grades IV/V). There is no
consensus about the timing and type of surgical correction. The outcome of open surgical correction is better than
endoscopic correction for higher grades of reflux, whereas
satisfactory results can be achieved by endoscopic injection
for lower grades.
There is no evidence that correction of persistent low-grade
reflux (grades IIII) without symptoms and normal kidneys
offers a significant benefit. These patients may be candidates for endoscopic treatment.
In all children presenting at age 15 years, CAP is the preferred option for initial therapy. For those with high-grade
reflux or abnormal renal parenchyma, surgical repair is
a reasonable alternative. In patients with lower grades of
reflux and without symptoms, close surveillance without
antibiotic prophylaxis may be an option.
A detailed investigation for the presence of LUTD should
be performed in all children after toilet-training. If LUTD is
found, the initial treatment should always be for LUTD.
If parents prefer definitive therapy to conservative management, surgical correction may be considered. Endoscopic
treatment is an option for all children with low grades of
reflux.
The traditional approach of initial medical treatment after
diagnosis and shifting to interventional treatment in case of
breakthrough infections and new scar formation needs to
be challenged, because the treatment should be tailored to
different risk groups.
The choice of management depends on the presence of
renal scars, clinical course, grade of reflux, ipsilateral renal
function, bilaterality, bladder function, associated anomalies of the urinary tract, age, compliance, and parental preference (79). Febrile UTI, high-grade reflux, bilaterality, and
cortical abnormalities are considered to be risk factors for
possible renal damage. The presence of LUTD is an additional risk factor for new scars.
In high-risk patients who already have renal impairment, a
more aggressive, multidisciplinary approach is needed.
CAP = continuous antibiotic prophylaxis.
This short text is based on the more comprehensive EAU/ESPU Paediatric
Urology Guidelines (ISBN 978-90-79754-83-0), available at their website,
http://www.uroweb.org.
Table 2: Management and follow-up according to

different risk groups
Risk
Groups
Presentation
Initial treatment
High
Symptomatic male or
female patients after
toilet-training with
high-grade reflux
(grades IV/V), abnormal kidneys and LUTD
Initial treatment is
always for LUTD;
intervention may be
considered in cases
of recurrent febrile
infections or persistent
reflux
Intervention should be
considered
High
Symptomatic male or
high-grade reflux
(grade IV/V), abnormal
kidneys and no LUTD
Moderate Symptomatic male or
female patients before
toilet-training, with
high-grade reflux and
abnormal kidneys
CAP is the initial treatment. Intervention

may be considered in
cases of breakthrough
reflux
Moderate Asymptomatic patients CAP is the initial treat(PNH or sibling) with ment. Intervention
high-grade reflux and may be considered in
cases of breakthrough
abnormal kidneys
reflux
Follow-up
Greater possibility of earlier
intervention
More aggressive follow-up

for UTI and LUTD; full reevaluation after 6 months
Open surgery has better results Postoperative VCUG on

than endoscopic surgery
indication only; follow-up
of kidney status until after
puberty
Spontaneous resolution is
higher in males
Follow-up for UTI/hydronephrosis; full re-evaluation after 1224 months
Follow-up for UTI/hydronephrosis; full re-evaluation after 1224 months
always for LUTD.
Intervention may be
considered in cases of
breakthrough infections or persistent
reflux
Choice of treatment
is controversial.
Endoscopic treatment
may be an option.
low-grade reflux,
abnormal kidneys with LUTD treatment
should be given if
or without LUTD
needed.
Moderate All symptomatic
always for LUTD
patients with normal
kidneys, with lowgrade reflux, with
LUTD
No treatment or CAP
Low
All symptomatic
kidneys, with lowgrade reflux, with no
LUTD
No treatment or CAP
Low
All asymptomatic
in infants
kidneys with low-grade
reflux
toilet-training, with
high-grade reflux and
normal kidneys with
LUTD
PNH = prenatal diagnosed hydronephrosis.
In case of persistent LUTD,

despite urotherapy, intervention should be considered. The
choice of intervention is controversial
Follow-up for UTI and

LUTD, kidney status; full
re-evaluation after successful urotherapy
Follow-up for UTI, LUTD,

and kidney status until
after puberty
Follow-up for UTI and

LUTD
If no treatment is given, parents should be informed about

risk of infection
Follow-up for UTI
If no treatment is given, parents should be informed about

risk of infection
Follow-up for UTI
Disclaimer
The European Association of Urology (EAU) Clinical Guidelines
published by the EAU Guidelines Office are systematically developed
evidence statements incorporating data from a comprehensive literature
review of the most recent studies available (up to their publication date).
The aim of clinical guidelines is to help clinicians to make informed
decisions about their patients. However, adherence to a guideline does
not guarantee a successful outcome. Ultimately, healthcare professionals
must make their own treatment decisions about care on a case-bycase basis, after consultation with their patients, using their clinical
judgement, knowledge and expertise. A guideline is not intended to take
the place of physician judgment in diagnosing and treatment of particular
patients.
Guidelines may not be complete or accurate. The EAU and their
Guidelines Office, and members of their boards, officers and employees
disclaim all liability for the accuracy or completeness of a guideline,
and disclaim all warranties, express or implied to their incorrect use.
Guidelines users always are urged to seek out newer information that
might impact the diagnostic and treatment recommendations contained
within a guideline.
Due to their unique nature as international guidelines, the EAU
Guidelines are not embedded within one distinct healthcare setting
- variations in clinical settings, resources, or common patient
characteristics, are not accounted for.
399
400
These Guidelines are edited for the EAU Guidelines Office

ISBN-13: 978-90-79754-99-1
Cover image: courtesy of Gunnar Aus - Sweden.
Printed by: Drukkerij Gelderland bv, Arnhem - the Netherlands.
Copyright European Association of Urology 2012
No part of this publication may be reproduced, stored in a retrieval system, or
transmitted by any means, electronic, mechanical or photocopying without written
permission from the copyright holder.

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The Guidelines Office Board and contributors endeavour

EAU Guidelines Office Board

The European Association of Urology use the following

Table 1: Level of evidence*

Table 2: Grade of recommendation*

Non-muscle Invasive Bladder Cancer

Upper Urinary Tract Urothelial Cell Carcinomas

Muscle-invasive and Metastatic Bladder Cancer

Management of Male LUTS,

incl. benign prostatic obstruction

Male Sexual Dysfunction:

Erectile Dysfunction and Premature Ejaculation

GUIDELINES ON NON-MUSCLEINVASIVE BLADDER CANCER

M. Babjuk, W. Oosterlinck, R. Sylvester, E. Kaasinen,

the TNM Classification of Malignant Tumours, 7th Edition,

Table 1: TNM classification 2009 for urinary bladder

Non-muscle-invasive Bladder Cancer

Characteristics of stages Ta, T1, and CIS

ferent degrees of anaplasia:

Table 2: 2004 WHO classification of non-invasive

malignant potential (PUNLMP) or as urothelial carcinomas,

Diagnosis and initial treatment steps

invasive urothelial carcinoma of the bladder (Eur Urol 2011

Prognostic factors and adjuvant treatment

Recommendations for low risk tumours

Recommendations for high risk tumours

Non-muscle-invasive Bladder Cancer

1. Complete TUR of papillary tumours followed by an

Intermediate risk tumours

Recommendations for intermediate risk tumours

1. Complete TUR followed by an immediate postoperative instillation with a chemotherapeutic agent

Table 3: Calculation of recurrence and progression

Non-muscle-invasive Bladder Cancer

Table 4: Probability of recurrence and progression

Prob. recurrence 1 year

Prob. recurrence 5 years

16 Non-muscle-invasive Bladder Cancer

Recommendations for the treatment of CIS

Non-muscle-invasive Bladder Cancer

3. After the 6 week induction course, a second course B

Follow-up for non-muscle-invasive bladder tumours

a very important prognostic factor for recurrence and for

Recommendations for follow-up cystoscopy

Non-muscle-invasive Bladder Cancer

Patients with CIS should be followed up for life due

20 Non-muscle-invasive Bladder Cancer

GUIDELINES ON UPPER URINARY

Upper Urinary Tract Urothelial Cell Carcinomas

Table 1: TNM classification 2009 for renal pelvis and

22 Upper Urinary Tract Urothelial Cell Carcinomas

N - Regional lymph nodes

Recommendations for diagnosis of UUT-UCC

Recommendations for radical management of UUT-UCC:

RNU = radical nephroureterectomy.

Recommendations for conservative management

MDCT = multidetector computed tomography.

26 Upper Urinary Tract Urothelial Cell Carcinomas

Recommendations for follow-up of UUT-UCC patients

Upper Urinary Tract Urothelial Cell Carcinomas 27

MDCT urography every 6 months for 2 years and then C

28 Upper Urinary Tract Urothelial Cell Carcinomas

Figure 1: Proposed flowchart for the management of UUTUCC

Diagnostics evaluation: CT-urography,

Table 2: 2004 WHO classification of non-invasive

1. Complete TUR of papillary tumours followed by an

1. Complete TUR followed by an immediate postoperative instillation with a chemotherapeutic agent

Table 3: Calculation of recurrence and progression

Table 4: Probability of recurrence and progression

3. After the 6 week induction course, a second course B

Table 1: TNM classification 2009 for renal pelvis and

Figure 1: Proposed flowchart for the management of UUTUCC

Table 1: 2009 TNM classification of urinary bladder

Figure 1: Flowchart for the management for T2-T4a N0M0

Figure 2: Flowchart for the management of metastatic

Table 1: Tumour Node Metastasis (TNM) classification

T2b Tumour involves more than half of one lobe,

If present, specify site(s) and extra- or intra-prostatic