Urology & Oncology
Bladder cancer
Bladder cancer is the most common malignant tumour of the urinary tract, and the fourth most common cancer in men in North America. In Canada, around 12,500 new cases are diagnosed each year, with a male/female ratio of around 3 to 4:1 - although the prognosis for women is poorer overall, due to more frequent delayed diagnosis (hematuria is often wrongly attributed to a urinary tract infection or gynecological cause). Over 90 % of bladder cancers are urothelial carcinomas (formerly known as transitional cell carcinomas) - developed from the urothelium, the lining epithelium of the upper and lower urinary tracts. There are two main basic prognostic and therapeutic categories: non-muscle-infiltrating bladder tumours (NIMBT - stages Ta, T1, CIS), which account for 75 to 80 % of new cases and can be treated conservatively, but with a very high risk of recurrence (50 to 70 % at 5 years), and muscle-infiltrating tumours (MIBT - stages T2 to T4), which require radical surgery (total cystectomy) or conservative radio-chemotherapy, and have a far less favourable prognosis. The most frequent and characteristic warning sign is painless macroscopic hematuria - pinkish or blood-red urine with no associated pain - present in 80 to 85 % of cases at the time of diagnosis. This symptom, even if episodic or fleeting, should systematically prompt cystoscopy in all adults over 35, whatever their risk profile, as painless macroscopic hematuria can never be attributed to a benign cause without full investigation of the urinary tract.
Risk factors
- Smoking - the first modifiable risk factor: smoking is responsible for 50 to 65 % of bladder cancers in men and 20 to 30 % in women; tobacco carcinogens (aromatic amines, nitrosamines, polycyclic aromatic hydrocarbons) are eliminated in high concentrations in the urine - prolonged contact with the bladder urothelium; the risk is multiplied by 2 to 4 in active smokers versus non-smokers; stopping smoking gradually reduces the risk, but it remains high for 20 years after cessation
- Occupational exposure to aromatic amines: second leading cause of bladder cancer - responsible for 20 to 25 % of cases; high-risk occupations: chemical and petrochemical industries, dyeing and textile dyes (benzidine, beta-naphthylamine, 4-aminobiphenyl - IARC Group 1 carcinogens), rubber and plastics industries, hairdressers (old hair dyes), foundries, aluminum and paint industries; 15 to 40-year latency between exposure and cancer development; occupational disease declaration possible in Canada, depending on exposure table
- Urinary schistosomiasis (Schistosoma haematobium): main cause of squamous cell carcinoma of the bladder (non-urothelial) in endemic countries (sub-Saharan Africa, Middle East, Nile) - chronic inflammation of the bladder wall by parasite eggs → squamous cell metaplasia → carcinoma; accounts for 75 % of bladder cancers in Egypt
- Previous pelvic radiotherapy: previous treatment with pelvic radiotherapy (cervical, prostate, rectal cancer) → risk of radiation-induced bladder cancer × 2 to 4 - delay of 10 to 20 years after irradiation; systematically evoke hematuria in a patient with a history of pelvic radiotherapy
- Cyclophosphamide (alkylating agent): chemotherapy with cyclophosphamide → urotoxic metabolite (acrolein) excreted in urine → chronic haemorrhagic cystitis → urothelial cancer (risk × 9 after prolonged use); prevention by hyperhydration and MESNA (sodium 2-mercaptoethanesulphonate) during chemotherapy courses; 5 to 15 year delay
- Pioglitazone (antidiabetic - thiazolidinedione): pharmacovigilance signal confirmed in several epidemiological studies - increased risk of bladder cancer (× 1.2 to 1.4) with prolonged use > 24 months; withdrawn or not recommended in certain countries; contraindicated if history of or risk factor for bladder cancer according to Health Canada.
- Aristolochia (aristolochic acid): plant used in traditional Asian medicine and in certain fraudulent weight-loss diets - powerful urothelial carcinogen (aristolochia nephropathy + cancer of the upper urinary tract and bladder); numerous cases described in Belgium, Taiwan and China
- Chronic urinary tract infections and bladder stones: chronic inflammation of the bladder mucosa → increased risk of squamous cell carcinoma (less frequent than urothelial carcinoma); patients with long-term indwelling bladder catheters (paraplegics, neurological bladder)
Symptoms
- Painless macroscopic hematuria: cardinal symptom present in 80 to 85 % of bladder cancers at the time of diagnosis - pinkish, bright red or reddish-brown urine (port- or Coca-Cola-colored hematuria) without associated pain; absence of pain is characteristic and should point to a neoplastic rather than infectious cause (where hematuria is often accompanied by micturitional burning); hematuria may be episodic, intermittent, spontaneously resolving - it may disappear for several weeks before reappearing - this intermittent nature should in no way be reassuring and lead to no further investigation
- Isolated microscopic hematuria: detected by dipstick or ECBU (erythrocytes > 3/field) without urinary symptoms - reveals bladder cancer in 5 to 10 % of cases in patients over 50 with risk factors; warrants cystoscopy and upper urinary tract imaging in any adult over 35 with risk factors (smoking, occupational exposure) or over 50 with no identified risk factor
- Irritative bladder symptoms (irritative syndrome): pollakiuria, urgency, dysuria - present in 20 to 30 % of bladder cancers, especially in carcinoma in situ (CIS) and high-grade multifocal tumors; often mistakenly attributed to urinary tract infection or bladder overactivity - repeated negative ECBU in a patient with persistent irritative syndrome should prompt cystoscopy.
- Symptoms of locally advanced forms: pelvic or lumbar pain (pelvic wall invasion or ureteral obstruction); bilateral hydronephrosis (ureteral meatus obstruction → obstructive renal failure); lower limb edema (lymphatic or venous compression); urinary retention (bladder neck obstruction).
- Metastatic symptoms: bone pain (bone metastases - pelvis, rachis, femur); inguinal or supra-clavicular adenopathy; cough, dyspnea (lung metastases); jaundice (liver metastases); altered general condition, weight loss, cachexia.
ℹ️
Any painless macroscopic haematuria in an adult over 35 years of age should be considered neoplastic until proven otherwise, and investigated by cystoscopy and urinary tract imaging - even if it's a single, fleeting occurrence, or if another benign explanation seems obvious (urinary tract infection, anticoagulants). Attributing it to a urinary tract infection without a full urological investigation is one of the main causes of delayed diagnosis of bladder cancer.
Diagnosis and assessment
- Cystoscopy : reference examination - direct visualization of the bladder mucosa through the urethra (flexible or rigid cystoscope); location, macroscopic appearance (papillary vs. solid vs. flat), number and size of lesions; biopsies of suspected lesions and randomized biopsies of normal-appearing areas if CIS suspected; blue-light cystoscopy (fluorescence hexaminolevulinate - Cysview/Hexvix) - improves detection of flat lesions (CIS) and small-volume tumors not visible in white light; narrow-light cystoscopy (NBI) - alternative to blue light
- Diagnostic and therapeutic trans-urethral resection of bladder tumors (TURV): endoscopic resection of all visible lesions under general anaesthesia; resection specimen sent to anatomopathology for determination of histological type, grade (low grade vs. high grade - WHO 2004 classification) and depth of invasion (T stage - presence or absence of detrusor muscle in specimen) ; absence of detrusor muscle in the resection specimen = incomplete RTUV → re-RTUV mandatory 4 to 6 weeks later; urine cytology on fresh urine (3 consecutive samples) - high sensitivity for high-grade and CIS (85-90 %) but low for low-grade (20-30 %)
- Extensional imaging : thoraco-abdomino-pelvic CT scan with injection (3-phase uro-CT scan) - local (invasion of peri-vesical fat, adjacent organs) and distant (lymph nodes, liver, lungs, bone) extension; assessment of upper urinary tract (synchronous urothelial tumors in 5 % of cases) ; pelvic MRI - better resolution than CT for assessment of muscle invasion (T2 vs T3) and extension to adjacent organs; bone scan if symptoms suggestive of bone metastases.
- Urinary markers: NMP22 (nuclear matrix protein 22), BTA (bladder tumor antigen), urinary FISH (UroVysion - detection of chromosomal abnormalities in urothelial cells) - variable sensitivity and specificity; used as a complement to urinary cytology for monitoring high-risk NSTEMI and reducing the frequency of surveillance cystoscopies (not yet replaced by circulating tumor DNA tests in current practice).
Classification and treatment according to stage
| Stadium | Description | Reference treatment |
|---|---|---|
| Your low grade | Low-grade, non-invasive papillary tumor - favorable prognosis, low risk of progression | complete TURV; single endovesical instillation of mitomycin C within 24 hours of TURV (reduces risk of recurrence by 40 %); cystoscopic monitoring at 3 months, 6 months and then annually depending on progress |
| Ta high grade / T1 / CIS | High-grade or lamina propria invasion (T1) or carcinoma in situ (CIS - high-grade flat lesion, highly recurrent) - significant risk of muscle progression | RTUV + re-RTUV at 4-6 weeks (mandatory); intravesical instillations of BCG (bacille Calmette-Guérin): induction 6 weeks + maintenance 1-3 years (SWOG maintenance protocol) - reduces risk of progression by 30-40 %; early total cystectomy discussed if multifocal CIS refractory to BCG or recurrent high-grade T1 |
| T2 (superficial muscle invasion) | Invasion of superficial (T2a) or deep (T2b) detrusor muscle - muscle infiltrating tumor (TVIM) | Neoadjuvant cisplatin-based chemotherapy (dose-dense MVAC or gemcitabine-cisplatin, 3-4 cycles) + total radical cystectomy with extensive lymph node curage - 5-8 mortality reduction %; OR conservation radio-chemotherapy (RTCC) for patients ineligible for cystectomy or refusing radical surgery - TMT protocol (trimodality therapy : maximum TUR + radiosensitizing chemotherapy + radiotherapy 64-66 Gy) - 5-year survival similar to cystectomy in selected cases |
| T3-T4 (peri-vesical or adjacent extension) | Invasion of peri-vesical fat (T3) or adjacent organs - prostate, uterus, vagina, pelvic wall (T4) | Neoadjuvant chemotherapy (if cisplatin-eligible) + radical cystectomy (if resectable) OR radio-chemotherapy; if T4b (fixed wall) → induction systemic chemotherapy then reassessment of resectability |
| Stage IV (metastatic) | Distant lymph nodes or visceral metastases | 1st-line cisplatin-eligible: gemcitabine + cisplatin (GC) ± pembrolizumab (KEYNOTE-361) or nivolumab (CheckMate-901); 1st-line cisplatin-ineligible: pembrolizumab (KEYNOTE-052 - response 29 %) or atezolizumab if PD-L1+; 2nd-line: pembrolizumab (KEYNOTE-045) - median survival 10.3 months vs. 7.4 months chemotherapy; enfortumab vedotin (EV - anti-Nectin-4, ADC) - response 40-52 % in 2nd-3rd line; EV + pembrolizumab (EV-302) - FDA 2024 approved in metastatic 1st line - therapeutic revolution (median survival 31.5 months vs. 16.1 months GC) |
Post-treatment monitoring of NMVT
- Risk of recurrence and progression: NMVT recurs in 50 to 70 % of cases at 5 years after RTUV alone (without BCG) - which is why regular cystoscopic monitoring is essential; the risk of progression to a musculoinvasive tumor is 15 to 40 % depending on grade and initial stage; risk stratification (low, intermediate, high risk according to EORTC or CUETO tables) guides monitoring frequency and indications for adjuvant instillations.
- Cystoscopic monitoring protocol (high-risk): cystoscopy + urinary cytology at 3 months post-RTUV; if negative: cystoscopy every 3 months for 2 years, then every 6 months for 3 years, then annual for life; annual uro-CT for upper urinary tract monitoring (risk of upper tract urothelial tumor of 2-4 % at 5 years).
- BCG-refractory or BCG-ineligible: intravesical pembrolizumab (KEYNOTE-676) - positive trial published 2024; nadofaragen firadenovec (recombinant adenovirus expressing intravesical IFN-α2b) - FDA-approved 2023 for BCG-refractory CIS; radical cystectomy if progression despite conservative treatment.
Prognosis - 5-year survival
| Stage at diagnosis | Survival to 5 years | Remarks |
|---|---|---|
| TVNIM Ta-T1-CIS | 85-95 % | Excellent survival but frequent recurrence (50-70 %) - chronic disease requiring lifelong monitoring; muscle progression in 15-40 % of high-risk cases |
| T2 (superficial muscle) | 60-75 % | Radical cystectomy + neoadjuvant chemotherapy; improved survival compared with surgery alone |
| T3-T4 (locally advanced) | 25-45 % | Surgery possible in some cases; neoadjuvant chemotherapy essential |
| Stage IV (metastatic) | 5-15 % | Bleak prognosis until 2024; EV + pembrolizumab (EV-302) transformed prognosis - median survival 31.5 months (vs. 16.1 months with GC); hope for further improvement with next-generation ADCs |
Gross hematuria - consult immediately
Any painless macroscopic hematuria (pink or red urine without urinary burning) in an adult over 35 years of age should lead to a medical consultation within a few days for cystoscopy and imaging of the urinary tract - even if it's a single, brief occurrence, or if a benign cause seems likely. A macroscopic hematuria should never be assumed to be due to a urinary tract infection or physical exertion without a full urological investigation. A delay of several months in the diagnosis of bladder cancer can transform a curable NSVT into a poor-prognosis NSVT. Please call 911 if hematuria is very abundant with clots, acute urinary retention or signs of hemorrhagic shock.
Consult at Clinique Omicron
Clinique Omicron's doctors assess any episode of hematuria, prescribe the initial work-up (ECBU, CBC, creatinine, urinary tract ultrasound) and refer to the partner urologist for cystoscopy and full urological management. Follow-up of patients treated for bladder cancer is coordinated with the specialized urology team. Consultations are available at our points of service in Quebec, as well as via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The contents of this page are provided for information purposes only and do not replace the advice of a qualified healthcare professional. Any macroscopic hematuria in an adult over 35 years of age warrants a full urological investigation without delay.
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