Prostatic Diseases and Male Voiding

Dysfunction
Clinical Phenotyping and Multimodal
Treatment of Men With Chronic
Prostatitis/Chronic Pelvic Pain
Syndrome From the Middle East and
North Africa: Determining Treatment
Outcomes and Predictors of Clinical
Improvement
Ahmad Majzoub, Mohammed Mahdi, Ibrahim Khalil, Ahmed Al Saeedi, and
Khalid Al Rumaihi
OBJECTIVE To evaluate the effectiveness of UPOINT based multimodal treatment on patients with chronic
prostatitis/chronic pelvic pain syndrome (CP/CPPS), and determine factors that could be associ-
ated with clinical improvement.
METHODS A retrospective study was conducted in Doha, Qatar including patients with CP/CPPS from the
Middle East and North Africa. The UPOINT phenotyping system was used to classify patients
and guide their multimodal therapy. NIH-CPSI scores were computed initially and after 3 months
of treatment, and predictors of clinical improvement were assessed.
RESULTS The total NIH-CPSI improved significantly with a mean reduction of 8.21 after 3 months of treat-
ment (P < .001). 66.2% of patients had a clinical improvement demonstrated as a total NIH-
CPSI score reduction by at least 6 points after 3 months of treatment. No significant association
was found between clinical improvement, and extent of pain (ORa = 1.198, 95% CI 0.392-3.662,
P = .751), initial total NIH-CPSI (ORa = 0.983, 95% CI 0.886-1.089, P = .738), number of posi-
tive UPOINT domains (ORa = 0.871, 95% CI 0.451-1.681, P = .681), and number of prescribed
therapies (ORa = 1.118, 95% CI 0.699-1.789, P = .641).
CONCLUSION UPOINT phenotyping and directed therapy is associated with an important improvement in the
CP/CPPS. Therapeutic response does not appear to related to age or ethnicity. Clinical improve-
ment is also not predicted by initial extent and severity of the disease, whether relating to NIH-
CPSI or the number of positive UPOINT phenotypes, neither to the number of therapies involved
in the multimodal treatment strategy. UROLOGY 167: 179−184, 2022. © 2022 Elsevier Inc.

C
hronic prostatitis (CP) is characterized by a wide
range of clinical manifestations that substantially
affects the quality of life (QoL). Four categories
of prostatitis syndrome are identified by the National
Institutes of Health (NIH) and include acute bacterial
prostatitis (Category I), chronic bacterial prostatitis (Cat-
egory II), chronic nonbacterial prostatitis or chronic
From the Department of Urology, Hamad Medical Corporation, Doha, Qatar; and the
Department of Clinical Urology, Weil Cornell Medicine -Qatar, Doha, Qatar
Address correspondence to: Ahmad Majzoub, M.D., F.E.C.S.M., Department of
Urology, Hamad Medical Corporation PoBox 3050, Doha, Qatar.. E-mail: dr.
amajzoub@gmail.com
Submitted: February 28, 2022, accepted (with revisions): April 24, 2022
pelvic pain syndrome (CP/CPPS) (Categories IIIA and
IIIB), and asymptomatic inflammatory prostatitis (Cate-
gory IV).1
The third category of CP or CP/CPPS is a common dis-
order with a prevalence ranging between 2.2% and
13.8%. It frequently affects men who are younger than
50 years of age, though the exact etiology remains poorly
understood.2 The disease appears to be multifactorial in
origin and has a divergent spectrum of clinical presenta-
tions that commonly manifest as chronic pain alongside
voiding difficulties, erectile and ejaculation dysfunction,
and psychiatric symptoms.3 Consensus guidelines divide

© 2022 The Author(s). Published by Elsevier Inc. https://doi.org/10.1016/j.urology.2022.04.028 179

This is an open access article under the CC BY license. 0090-4295
(http://creativecommons.org/licenses/by/4.0/)
CP/CPPS into an early stage characterized by persistent or
recurrent symptoms for less than 6 months with no previ-
ous use of antibiotics, and a late stage characterized by per-
sistent or recurrent symptoms for more than 6 months that
are refractory to first line treatment.4
CP/CPPS is a diagnosis of exclusion, hence all other
etiologies of a patient’s pain and lower urinary tract symp-
toms (LUTS) such as stones, tumors, and strictures must
be assessed and treated when possible.4 The disease care
process is complex and clinical outcomes are usually not
satisfactory, owing to the heterogenous nature of symp-
toms between patients and insufficient specific diagnostic
markers.5,6 In fact, routine management models are not
specifically defined and the CP/CPPS generally fails
monotherapy due to the variable disease etiology and clin-
ical progression. Consequently, clinical phenotyping and
individualization of the therapy are highly suggested.7
The urinary, psychosocial, organ‑specific, infection, neu-
rological/systemic and tenderness (UPOINT) phenotype
system was developed in 2009 by Shoskes et al. as a novel
diagnostic and therapeutic algorithm to classify CP/CPPS
and establish multimodal phenotype-based treatment
plans.5 The UPOINT system is composed of 6 domains
that provide a phenotyping algorithm based on the urinary
manifestations, psychosocial abnormalities, organ‑specific
symptoms, infection-related symptoms, neurological/sys-
temic dysfunction, and skeletal muscles’ tenderness. The
patient symptoms and disease progression are linked to
each domain to provide a clinical diagnosis and recom-
mend a phenotype specific therapy.8
Several studies validated the UPOINT system and
showed that the number of positive domains in the system
correlate with increasing NIH-Chronic Prostatitis Symp-
tom Index (NIH-CPSI).9-12 The UPOINT-based pheno-
typing and directed therapy was reportedly associated with
substantial improvement in the CP/CPPS symptoms.10
Nevertheless, literature on the determinants of a
UPOINT-based therapy outcomes remains scarce and very
limited data are available especially from Middle East and
North Africa. This was a retrospective study that aimed to:
(1) evaluate the effectiveness of the CP/CPSS therapy
based on the UPOINT phenotype classification system;
and (2) determine factors that could predict the clinical
improvement of symptoms following multimodal therapy.
METHODS
Study Design and Participants
A retrospective study was conducted at the pelvic pain unit of the
urology department at Hamad Medical Corporation (HMC),
Doha, Qatar. The pelvic pain unit was established in August
2016 and, to the best of our knowledge, is the first to provide a
dedicated multidisciplinary service for patients with chronic pel-
vic pain in the region. Management is offered by a Urologist,
Physiotherapist and Psychiatrist with special interest and expertise
in this field of medicine. Patients with CP/CPPS who were diag-
nosed according to the NIH consensus guidelines for diagnosis of
CP/CPPS were included.13 While patients with other pre-
180
diagnosed forms of prostatitis that may overlap with the clinical
manifestations of CPPS including acute bacterial prostatitis,
chronic bacterial prostatitis, and asymptomatic prostatitis were
excluded. Additional exclusion criteria were patients with evi-
dence of antibiotic use within 2 weeks of their presentation, those
who underwent previous prostate surgery or who have an active
prostate cancer. The dates of diagnosis of these conditions were
verified against the medical profiles of the patients to preclude any
risk of selection bias. The institutional review board at HMC
approved the study protocol (protocol No. MRC-01-21-004), and
methods were enacted according to the institutional guidelines
and regulations. A waiver of signed informed consent was used.
Procedures and Variables
All patients were thoroughly evaluated with history and physical
examination. The initial NIH-CPSI score was computed at the
baseline. Pain was characterized according to its location,
description, triggering factors, and number of locations involved.
All psychosocial symptoms relating to pain, stress, anxiety,
depression, somatization symptoms, social aspects, substance
abuse, personality factors, trauma-related disorders, and QoL
were assessed and evaluated. LUTS were evaluated and infec-
tions were determined by culturing expressed prostatic secretions
(EPS). Bladder and prostatic specimens were also evaluated by
assessing midstream urine (VB2), and first 10 mL of voided urine
after EPS (VB3). Anatomical and pathological abnormalities
were determined by flexible cystoscopy when indicated, and cal-
cifications were examined by transrectal ultrasonography
(TRUS). The UPOINT phenotyping system was used to classify
the patients and guide their multimodal therapy. Pharmacologi-
cal and non-pharmacological treatments included alpha block-
ers, antibiotics, antidepressants, anticholinergics, neuroleptics,
phytotherapy, physical therapy, low intensity extracorporeal
shockwave therapy (Li-ESWT), and mental health therapy.
NIH-CPSI score was computed after 3 months of treatment, and
clinical improvement was determined by a total score decline of
at least 6 points.14
Statistical Analysis
Data were analyzed by IBM Statistical Package for the Social
Sciences (SPSS, version 25). The demographic, clinical, and
therapeutic characteristics of patients were evaluated by descrip-
tive statistics. Continuous variables were assessed by their mean
( § standard deviation, SD), and median (interquartile range,
IQR). Categorical variables were assessed by their frequencies
and percentages. The Shapiro-Wilk test was used to assess the
normal distribution of variables. A paired sample T-test was used
to compare the NIH-CPSI scores at baseline and after 3 months
of treatment. The mean index difference was dichotomized at a
score of 6 to evaluate clinical improvement. Multivariable logis-
tic regression using enter method was run to determine the
demographic and clinical predictors of improvement. The results
were reported as adjusted odds ratio (ORa) and 95% CI. P values
of .05 and less were considered statistically significant with an
acceptable margin of error of 5%.
RESULTS
Demographic and Clinical Characteristics of Patients
A total of 193 patients were included in the study. The mean age
was 39.68 ( § 10.15), 55.4% were from Middle East, the median
duration of illness was 18 months, and 45.6% had psychosocial
UROLOGY 167, 2022
Table 1. Demographic and clinical characteristics of Table 2. UPOINT phenotype classification
patients Phenotype Frequency (%)
Frequency (%) or Urinary
Characteristic Mean ( § SD)/ Median (IQR) ▓ No 56 (29.0)
Age 39.68 (10.15) ▓ Yes 137 (71.0)
Region Psychosocial
▓ Middle East 107 (55.4) ▓ No 151 (78.2)
▓ North Africa 86 (44.6) ▓ Yes 42 (21.8)
Duration (mo) 18.00 (7.00-48.00) Organ confined
LUTS ▓ No 36 (18.7)
▓ Irritative 135 (69.9) ▓ Yes 157 (81.3)
▓ Obstructive 114 (59.1) Infection
TRUS calcification ▓ No 165 (85.5)
▓ Yes 13 (6.7) ▓ Yes 28 (14.5)
▓ No 17 (8.8) Neurogenic
Psychosocial symptoms 88 (45.6) ▓ No 181 (93.8)
Flexible cystoscopy ▓ Yes 12 (6.2)
▓ Performed cases 30 (15.5) Tenderness
▓ Normal result 5 (2.6) ▓ No 127 (65.8)
▓ Abnormal result 25 (13.0) ▓ Yes 66 (34.2)
EPS result Number of positive UPOINT domains
▓ Negative culture 55 (67.9) ▓ 1 38 (19.7)
▓ Positive culture 26 (32.1) ▓ 2 83 (43.0)
VB2* ▓ 3 51 (26.4)
▓ <5 WBC/HPF 155 (84.2) ▓ 4 20 (10.4)
▓ >5 WBC/HPF 29 (15.8) ▓ 5 1 (0.5)
VB3y
▓ <5 WBC/HPF 72 (39.6)
▓ >5 WBC/HPF 110 (60.4) extracorporeal shock wave therapy (ESWT). Supplementary
* Midstream urine specimen (bladder specimen). table 2 presents the full pharmacological and non-pharmacologi-
y cal therapies of the patients.
First 10 mL of voided urine after EPS (prostatic specimen).

symptoms. More than the half (69.9%) had irritative LUTS,
6.7% had calcification on TRUS, and 13% had abnormal result
on flexible cryptoscopic examination. Around one-third of the
patients (32.1%) had positive cultures of EPS, 15.8% had abnor-
mal white blood cell (WBC) count in the bladder specimen,
and 60.4% had abnormal WBC count in the prostatic specimen.
The patients’ demographic and clinical characteristics are shown
in Table 1.
NIH-Chronic Prostatitis Symptom Index
The initial total NIH-CPSI score was 26.26 ( § 6.57). The total
score improved significantly with a mean reduction of 8.21 after
3 months of treatment (P < .001). The pain, urinary, and quality
of life score of NIH-CPSI also significantly improved after 3
months with a mean score reduction of 3.97, 1.96, and 2.22
respectively. The paired sample T-test of the initial and 3-month
NIH-CPSI is shown in Table 3.

Pain Characteristics Predictors of Clinical Improvement

Greater than half of the patients had perineum pain (65.8%) fol-
lowed by penile pain (49.2%). Pain was described as burning or
compressing (33.7% and 30.1%) respectively. The pain was
mostly triggered by ejaculation (63.2%) followed by urination
(16.6%). For the extent of pain, around half of the patients had
less than 3 pain locations. SupplementaryTable 1 reports the
detailed pain characteristics of the patients.
UPOINT Phenotyping
Most of the patients (43%) had 2 UPOINT classification
domains. The majority (81.3%) were classified with the organ
confined phenotype, and 71% had the urinary phenotype.
Around one-third of patients (34.2%) had tenderness, and
21.8% had psychosocial symptoms. The UPOINT phenotyping
is reported in Table 2.
Multimodal Treatment Strategy
Both pharmacological and non-pharmacological therapies were
prescribed in the UPOINT directed therapy. Around 60% of the
patients were on alpha blockers and 35.2% were on antibiotics.
Phytotherapy and physical therapy were prescribed and utilized
by 44.6% and 20.7% respectively, and 33.7% of the patients had
Greater than half of the patients (66.2%) had a clinical improve-
ment demonstrated a total NIH-CPSI score reduction by at least
6 points after 3 months of treatment. Demographic and clinical
characteristics of the patients were not significantly associated
with clinical improvement. The extent of pain, initial NIH-
CPSI, number of positive UPOINT domains, and number of pre-
scribed therapies were also not significantly associated with clini-
cal improvement. Table 4 presents the multivariable logistic
regression of predictors of clinical improvement.
DISCUSSION
The current study examined the impact of UPOINT phe-
notyping and multimodal therapy on the clinical out-
comes of patients with CP/CPPS, and assessed predictors
of clinical improvement. We found that a UPOINT clas-
sification and directed therapy is associated with a sub-
stantial improvement in the clinical outcomes. No
significant associations between clinical improvement,
and the demographic and clinical characteristics of the
patients were determined. We also found no significant

UROLOGY 167, 2022 181

Table 3. Paired sample T-test of NIH-CPSI initially and after 3-month follow-up
Symptom Index Assessment Mean SD Mean Difference P value
Pain Initial 12.55 3.49 3.97 < .001
After 3 mo 8.58 4.22
Urinary Initial 5.71 2.83 1.96 < .001
After 3 mo 3.75 2.86
Quality of life Initial 7.82 2.23 2.22 < .001
After 3 mo 5.60 2.65
Total Initial 26.26 6.57 8.21 < .001
After 3 mo 18.05 8.44

association between clinical improvement, and the disease
severity according to pain extent, number of positive
UPOINT domains, and number of prescribed therapies
within the multimodal treatment strategy.
A UPOINT guided therapy improved the clinical out-
comes and was associated with a significant reduction in
the NIH-CPSI score. According to Propert et al therapeu-
tic effect can be determined at a highly sensitive and spe-
cific 6-point reduction of the total NIH-CPSI score.15 In
the present study, greater than half of the patients were
categorized as therapeutic responders whilst they achieved
this perceivable score improvement. The response rate
was slightly higher compared to other results from the Far
East that determined clinical improvement at a 6-point
score decline in exactly 50% of the patients.16 Although
this study had higher initial pain, urinary, QoL, and total
NIH-CPSI score compared to that study, our multivari-
able analysis showed that clinical improvement is not pre-
dicted by the initial total symptom index.
CP/CPPS is commonly linked to ejaculatory pain or pel-
vic discomfort with conspicuous LUTS.17 Our findings
showed that CP/CPPS is largely described as burning and
compressing, and extends to less than 3 locations primarily
the perineum and penis. Fewer locations of pain involve-
ment and irritative rather than obstructive LUTS appear to
be associated with higher odds of response to multimodal
therapy, however, this association was not statistically signifi-
cant. Although this study included relatively younger
patients compared to other studies,10,18-20 our results do not
appear to be confounded by age as the multivariable analysis
showed no significant association between age and clinical
improvement. Moreover, whilst having a heterogenous pop-
ulation from different regions, our findings suggest that
ethnicity does not link to symptom index improvement.
Therefore, we hypothesize no role of genetics in determining
clinical response to CP/CPPS treatment.
The multimodal therapeutic strategy in this study
involved a blend of pharmacological and non-pharmaco-
logical treatments and depending mostly on alpha block-
ers. In a pooled analysis, alpha blockers were associated
with a significant improvement of CP/CPPS symptoms.21
This can be explained by the overlapping nature of the
disease pathogenesis and over activation of alpha-adrener-
gic receptors, which warrant empirical utilization of alpha
blocking agents in the management of CP/CPPS.22 Nev-
ertheless, the utilization of any monotherapy is reportedly
associated with insufficient response particularly when
compared to multimodal strategies.23 Our findings add to
the literature that clinical response to a UPOINT directed
therapy is related to qualitative rather than quantitative
multimodal strategies, as our multivariable analysis
showed no significant association between the number of
prescribed therapies and clinical improvement.
Previous literature reported a significant strong correlation
between the number of positive UPOINT domains and ini-
tial NIH-CPSI total score.5,18-20 We determined that
patients could have greatly 2 UPOINT phenotypes. While
the number of positive UPOINT domains is evidently linked
to disease severity, the current study adds to the literature
that the number of positive domains does not have a signifi-
cant impact on the NIH-CPSI posttherapy score and there-
fore does not predict clinical improvement.
Strengths and Limitations
No previous reports evaluated the utility of the UPOINT
system on patients from Middle East and North Africa.

Table 4. Multivariable logistic regression of predictors of clinical improvement

95% confidence Interval
P value
Variable ORa Lower Upper
Age 1.008 0.947 1.072 .812
Region (Middle East vs North Africa) 0.620 0.204 1.887 .400
Duration of disease 1.003 0.993 1.013 .544
Pain extent (reference: >3 locations) 1.198 0.392 3.662 .751
Initial Total NIH CPSI 0.983 0.886 1.089 .738
Number of positive UPOINT domains 0.871 0.451 1.681 .681
LUTS: irritative (No vs Yes) 1.535 0.432 5.450 .507
LUTS: obstructive (No vs Yes) 0.578 0.181 1.846 .355
Number of prescribed therapies 1.118 0.699 1.789 .641

182 UROLOGY 167, 2022

The design of the study allowed to establish temporality of
associations and thus determine causality. The sample size
was adequate to allow for multivariable analysis to deter-
mine predictors of clinical outcomes while eliminating
potential confounders. On the other hand, few limitations
could be reported. The retrospective nature of the study
can be considered as one limitation. The clinical out-
comes were measured only after 3 months of treatment
and therefore the current study did not determine long
term predictors of maintaining clinical response. Further
research is suggested in this context to follow-up patients
over an extended 1- to 5-year period to assess long term
fluctuations in NIH-CPSI with multimodal therapy, and
evaluate factors that could be associated with favorable
outcomes. In addition, residual confounders relating to
sexual dysfunction cannot be precluded. Sexual dysfunc-
tion is common in 40% to 70% of the CP/CPPS patients,
and can be associated with higher rates of depression and
anxiety.24-28 Addition of “sexual dysfunction” domain
into the UPOINT system is still controversial.8 Future
work will prospectively evaluate the use of the UPOINT
plus “sexual dysfunction” system in the treatment of CP/
CPPS.
CONCLUSION
The UPOINT classification and directed therapy is associ-
ated with an important improvement in the symptoms
and thus QoL over a sensitive and specific cutoff point of
the NIH-CPSI. Therapeutic response does not appear to
related to age or ethnicity. Similarly, clinical improve-
ment is not predicted by initial extent and severity of the
disease, whether relating to NIH-CPSI or the number of
positive UPOINT phenotypes, neither to the number of
therapies involved in the treatment strategy. This under-
scores the value of the UPOINT phenotype directed ther-
apy as an approach associated with measurable significant
improvement in patients’ symptoms.
SUPPLEMENTARY MATERIALS
Supplementary material associated with this article can
be found in the online version at https://doi.org/10.1016/
j.urology.2022.04.028.
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