CRS: HEMATURIA

Group 3
HISTORY

CHIEF COMPLAINT
- Mr L, a 69 years old Chinese gentleman with a newly suspected bladder
tumor was electively admitted to the hospital on 10/5/2022 for TURBT
with the initial presentation of painless hematuria 2 months ago
HOPI
- 2 months ago, he noticed blood in his urine
- Painless
- It was persistent for 1 whole day
- The blood was noticed at the beginning or end of the urine
- He noticed dribbling and weak stream of his urine since Jan 2022
- However, there was NO other LUTS sx like increased in frequency, nocturia, urgency, straining,
hesitancy or incomplete emptying
- NO anaemic symptoms like light headedness, chest pain or SOB
- NO constitutional symptoms like LOA and LOW
- NO fever
- NO systemic symptoms like bone pain, jaundice or altered bowel habit
- NO history of urinary stone or pelvic radiation
- This is NOT his first time noticing blood in urine
- For the past 3 years, there have been few episodes where he noticed blood in his urine
- However, it resolves on its own and does not persist
- He have been to the GP, but only treated as UTI
- 2 months ago, he came to PPUM for the persistent hematuria
- Ultrasound and cystoscopy was done, found a left wall bladder tumor
- Subsequently did a CT renal 4 phase : suggest a locally invasive bladder tumor
PAST MEDICAL HISTORY
1. BPH in 2014
- Done TURP in 2014 at PPUM
- On follow up at PPUM

1. Caecum Cancer
- Diagnosed in 2016
- Done right hemicolectomy in UMSC
- No adjuvant therapy
- Last colonoscopy done in feb 2022 → sigmoid polyp

1. Hypertension
PAST SURGICAL HISTORY

1. TURP IN 2014
2. Laparotomy for right hemicolectomy in 2016

*both surgery were uneventful

DRUGS AND ALLERGY

- Amlodipine 5 mg OD
- Takes herbs and chinese supplement
- No known allergy to any food or medication
FAMILY HISTORY

1. Father - lung cancer metastatic to liver

2. Mother - liver cancer
3. Brother - BPH
4. 2 sisters - both have ovarian tumor
Social history

- Does not smoke

- Drinks alcohol 1-2x a week with his friends while playing golf → 2-3 bottle of beers
- Retired IT worker in a bank 16 years ago
- Currently lives with wife in PJ
- Hobby is to play golf and travel
- Active lifestyle - walks 5 KM everyday
PHYSICAL EXAMINATION
General inspection

- Alert, conscious, pink and comfortable breathing in room air

- Branula at left hand connected to 0.9% normal saline
- CBD attached to a urinary bag → 1500ml , there was gross blood but no blood clots

Peripheries

- There was no koilonychia, leukonychia, Dupuytren's contracture, palmar erythema, palmar pallor or hepatic
asterixis.
- CRT less than 2 seconds and pulse was 68 beats per minute, regular rhythm and adequate volume.
- Temperature was warm and equal bilaterally.
- No scratch marks on the forearm
Face

- No conjunctival pallor or scleral icterus

- Good dental hygiene
- Tongue was mildly coated
- No angular stomatitis

Chest

- No spider naevi
- No loss of axillary hair
- No gynecomastia
Abdomen

- There is a midline scar of about 10 cm , well healed and no keloid formation

- No skin colour change
- No abdominal distention
- No hernia upon coughing
- There is no tenderness or mass felt in both superficial or deep palpation
- No hepatomegaly or splenomegaly
- Kidneys are not ballotable
- No shifting dullness
- Abdominal sound are present
- No renal bruit
- No sacral or pedal edema
Other examinations:

1. Digital rectal examination - to feel for the size and surface of prostate
2. Genitalia examination - any scrotal swelling
Investigation (10/5/2022)

Laboratory test

1. FBC
- Normal Hb and WCC
1. Coagulation profile
- PTT and aPTT not prolonged
1. Renal function test
- Urea and creatinine are not raised
- eGFR is 80
1. UFEME
- Hemoglobin - negative
- Leukocyte esterase and nitrite - negative
Imaging ( 23/3/2022)

1. CT renal 4 phase
- Features are suggestive of locally invasive urinary bladder cancer ,prostate origin, with suspicious
involvement of the left distal ureter.
- No CT evidence of distant metastasis.
- Stable prostatomegaly and right renal cyst.
Management

- TURBT done on 11/5/2022

Approach to haematuria

Definition

Gross haematuria - visible bloody or brown urine

Microscopic haematuria - >3 RBC per high powered field

History

HOPI

- Symptomatic (visible or non visible), amount, onset

- Rule out benign causes of haematuria : menstruation, trauma, sexual intercourse, food dye, drugs
(levodopa, rifampicin)
- When during urination does it occur?
- Initial : disease in the urethra
- Terminal : near bladder neck or prostatic urethra
- Throughout : in bladder or upper urinary tract
Lower urinary tract symptoms :

- Storage problem - irritative symptoms : frequency, urgency, nocturia

- Causes : UTI, stones, bladder tumour
- Voiding problems - obstructive symptoms : terminal dribbling, incomplete emptying,
intermittency, poor stream, straining to pass urine, hesitancy
- Causes : BPH, prostate cancer, urethral stricture
- Others : polyuria, oliguria, urethral discharge

Upper urinary tract symptoms :

- Loin pain / tenderness : renal infection, infarction, obstruction

- Severe loin to groin pain : acute obstruction of the renal pelvis or ureter
Severity

- Transient or persistent?
- Symptoms of anemia : pallor, chest pain, palpitation, SOB
- Any concomitant renal impairment : amount of urine

Physical examination

- Vitals
- Signs of anemia
- Abd - loin tenderness, mass, renal ischemia, palpable bladder, ballotable kidney
- Extremities - edema, rashes - more likely to be renal causes
- Inspect external genitalia and scrotum - blood at the urethra, varicocele
- DRE - BPH or prostate cancer
Causes of Haematuria (Post-renal)
Aetiology Example Relevant history

Trauma Recent urinary catheterisation, flexible cystoscopy, TURP

Infection UTI, cystitis, Irritative symptoms

prostatitis Dysuria, urethral discharge

Tumours Transitional cell Red flags for malignancies :

carcinoma, Male >35 y/o
prostate cancer, Past or current smoker
Occupational exposure to chemicals/dyes
Hx of exposure to carcinogenic agents or chemotherapy
Hx of gross haematuria, urological disease, chronic UTI, pelvic radiation

Stones Nephrolithiasis, Unilateral flank pain radiating to the groin

ureterolithiasis,

Benign prostate Advanced age with voiding problems

hyperplasia
Renal Causes of Haematuria

Features that suggest glomerular bleeding :

- Absent clots
- Frothy urine
- Proteinuria >500mg/day or 2+ urine dipstick
- Some RBC cast is present
Prostate cancer
Risk factors

Non-Modifiable

1) Advanced age (increases after 40 years old)

2) Ethnicity
3) Genetic factors (germline mutation in DNA repair genes, eg: BRACA 2)
4) Hormonal levels (Testosterone, DHT, Estradiol, growth of tumor can be inhibited with
orchidectomy or administration of oestrogens)
Modifiable

1) Diet (High animal fat, inadequate vegetable intake, High Soy intake, High Omega-3 fatty acid, fish
oil, large amounts of multivitamins, high serum vitamin B12 & folic acid, high in calcium & vitamin
D, high in vitamin E), associated but evidence is limited
2) Cigarette Smoking
3) Obesity
4) Physical Activity
5) Industrial Chemical exposure
Clinical presentation
Can be incidental (latent carcinoma) or symptomatic (clinical carcinoma)

Latent:

1) Incidentally detected microscopically (histological findings- biopsy for bph)

Symptomatic

2) Urinary symptoms: dysuria, hematuria, urgency, frequency, hesitancy, incontinence, retention, dribbling, straining)
3) Metastatic symptoms (bone pain, pathological fractures)- direct, hematogenous, lymphatics
4) Anemic symptoms ( palpitations, reduced effort tolerance, shortness of breath, chest pain)
5) Picked up on DRE (hard, irregular, nodular, asymmetrical area of induration, fixed to the wall)
6) Look out for ballotable kidneys (hydronephrosis), bone pain, jaundice, abdominal distention, pleural effusion &
lymphedema on physical examination
Investigation
Laboratory
FBC Anemia, thrombocytopenia, infection

RP Assess kidney function(creatinine,urea)

LFT Albumin level for nutritional status, serum ALP for bone mets, raise of transaminase for liver
mets

Serum PSA It is prognostic and monitoring marker for recurrence

Normal < 4ng/dL, >10ng/dL biopsy recommended
It is not specific, as it can be falsely elevated in
● BPH
● AUR
● UTI
● DRE
● Prostatitis

Serum calcium For bone mets

Urine FEME UTI - nitrite, leukocyte

Hematuria
*If positive for UTI -> Do Urine C&S
Imaging

Ultrasound KUB Look for obstructive uropathy, any hydronephrosis, hydroureter, check for prostate size

CT TAP For mets and staging

Multiparametric MRI For PIRADS scoring

Bone scan For mets and staging

TRUS biopsy Take 12 cores (left 6 + right 6) from peripheral zones of gland
(transrectal ultrasound ● SUMMATION SCORE (GLEASON Score)
guided biopsy)
○ 6-10 [addition of two score]
■ Gleason 6 or less : less aggressive
■ Gleason 7 or more : aggressive
Staging and grading

TNM staging

T - findings on DRE

T1 - non-palpable tumor

T1a - tumor incidental histopathological findings <5% of tissue resected

T1b - tumor incidental histopathological findings >5% of tissue resected

T1c - tumor identified on needle biopsy (elevated PSA levels)

T2 - palpable tumor confined to the prostate

T2a - less than half of one lobe

T2b - more than half of one lobe

T2c - both lobe

T3 - extends through prostate capsule

T3a - extracapsular extension

T3b - invades seminal vesicle

T4 - extends to adjacent structures (bladder wall, external sphincter, rectum, etc)

N - pelvic lymph nodes

Nx - cannot be assessed

N0 - no lymph node spread

N1 - present lymph spread

M - metastasis

M1 - Distant metastasis
Gleason Grading system

Based on histological architecture of resected tumor.

Gleason score is obtained by adding the grade score of the most extensive pattern (primary) grade and
second most common pattern (secondary) grade. If only 1 pattern is present, then just double the
number. If more than 2 pattern available, then add the grade of the most extensive pattern with the
highest grade, irrespective of pattern.

Gleason Score (GS) = ____ + ____. Range from 2-10.

Risk of recurrence
Management
 Management: localised cancer (T1-2)

Conservative

Active surveillance Watchful waiting

Curative intent Palliative intent

F/u at pre-defined schedule Patient-specific f/u

- DRE, PSA, MRI, re-biopsy - Non-specific, dependent on symp of
progression

> 10 yrs life expectancy < 10 yrs life expectancy

Only for low-risk patients Can apply to patients at ALL stages

Minimise treatment-related toxicity

Management: localised cancer (T1-2)

Curative (surgery or radiotherapy)

Radical prostatectomy +/- extended pelvic LN dissection

- Remove prostate & seminal vesicles, vesico-urethral anastomosis (bladder neck + urethra)
- Open, laparoscopic, robotic-assisted
- Complications:
- Urinary incontinence
- Erectile dysfunction
- Bladder neck stenosis
- Infection
Management: localised cancer (T1-2)

Radiotherapy

- External beam radiotherapy

- Brachytherapy: radioactive sources are implanted in prostate
- Side effects:
- Cystitis: haematuria, frequency, dysuria, urinary retention
- Rectal bleeding
- Diarrhoea
- Proctitis
Management: locally advanced (T3)
Radical prostatectomy + ePLND +/- adjuvant ADT or adj radiotherapy

Hormonal therapy: androgen deprivation therapy (ADT)

1. Surgical castration: bilateral orchidectomy

2. Medical castration:
- LHRH agonist: goserelin, leuprolide
- Flare-up 2-3 days after starting, lasts 1wk; reach castration level in 2-4 wks
- SE: hot flush, weight gain, reduced libido, ED, CVS risk
- LHRH antagonist: degarelix
- Reach castrate level in 3 days
- Anti-androgen:
- Steroidal: cyproterone acetate > SE: CVS risk, hepatotoxic
- Non-steroidal: bicalutamide >SE: gynaaecomastia
- New androgen pathway-targeting agents:
- To target castrate-resistant cancer
- Eg: abiraterone acetate, enzalutamide
Management: metastatic cancer

ADT + systemic treatment

1. ADT + docetaxel
2. ADT + abiraterone acetate + prednisolone*

*prednisolone is to prevent hyperaldosteronism secondary to upregulation of HPA axis

3. ADT + apalutamide/ enzalutamide

Management: castrate-resistant prostate cancer
Castrate serum testosterone < 50 ng/dL or 1.7 nmol/L plus either:

a. Biochemical progression: Three consecutive rises in PSA at least one week apart resulting in two
50% increases over the nadir, and a PSA > 2 ng/mL

or

b. Radiological progression: The appearance of new lesions: either two or more new bone lesions
on bone scan or a soft tissue lesion using RECIST (Response Evaluation Criteria in Solid Tumours)

Treat with:

- Docetaxel, abiraterone acetate, enzalutamide (whichever is not used before)

- Immunotherapy
Summary of management
Localised Locally advanced Metastatic Castrate-resistant

Active surveillance Radical ADT + docetaxel Docetaxel

prostatectomy +
ePLND

Radical Adj radiotherapy ADT + abiraterone Abiraterone acetate

prostatectomy acetate

Radiotherapy Adj ADT ADT + enzalutamide Enzalutamide

Watchful waiting Watchful waiting Watchful waiting Immunotherapy

Thank you