Bladder Cancer — Causes, Symptoms, Diagnosis & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Bladder cancer is a malignancy arising from the transitional (urothelial) epithelium lining the bladder. The vast majority (90-95%) are urothelial carcinomas (UC — formerly called transitional cell carcinomas); other histological types include squamous cell carcinoma (associated with schistosomiasis and chronic irritation) and adenocarcinoma (rare). Bladder cancers are classified by the depth of muscle invasion, which determines treatment: non-muscle-invasive bladder cancer (NMIBC — Ta, T1, carcinoma in situ — confined to the urothelium and lamina propria; approximately 75% of newly diagnosed cases; good prognosis but high recurrence rate) and muscle-invasive bladder cancer (MIBC — T2 and above — invades the detrusor muscle; higher metastatic potential; requires radical treatment). The most common presenting symptom is painless visible haematuria (macroscopic haematuria — any episode in an adult warrants urgent 2-week wait urology investigation). Bladder cancer has among the highest recurrence rates of any cancer — requiring lifelong surveillance cystoscopy in non-muscle-invasive disease.

Tobacco smoking: the most important and common risk factor — approximately 50% of bladder cancer cases in the UK are attributable to smoking; carcinogens in tobacco (aromatic amines, polycyclic aromatic hydrocarbons) are excreted in urine and are in direct contact with the urothelium; risk is dose-dependent and 2-4 times higher in smokers vs non-smokers; cessation reduces risk over time but does not fully normalise it. Occupational carcinogen exposure: aromatic amines (2-naphthylamine, benzidine, 4-aminobiphenyl) in the rubber, dye, leather, printing, and aluminium industries — accounts for approximately 10-20% of bladder cancers; latency period of 20-45 years between exposure and cancer development. Advancing age: most cases occur in people over 60 (median age at diagnosis approximately 70 years). Male sex: men are 3-4 times more likely to develop bladder cancer (higher smoking rates, occupational exposure, and hormonal factors). Previous bladder cancer: highest single risk factor for new tumours — patients require lifelong cystoscopic surveillance. Chronic bladder inflammation: Schistosoma haematobium infection (endemic in Africa and Middle East — causes squamous cell carcinoma); recurrent urinary tract infections; long-term catheterisation. Cyclophosphamide chemotherapy (metabolite acrolein is a direct urothelial carcinogen — chronic exposure causes haemorrhagic cystitis and bladder cancer; mesna uroprotection used during treatment). Pelvic radiation therapy (for cervical, rectal, or prostate cancer — increases bladder cancer risk). Aristolochic acid nephropathy (endemic Balkan nephropathy — causes upper urinary tract urothelial carcinoma). Genetic and family history (rarely — TP53, FGFR3, RB1 mutations important prognostically; Lynch syndrome increases UUT and bladder urothelial cancer risk).

Painless visible haematuria (macroscopic haematuria): the cardinal and most common presenting symptom — present in 80-85% of bladder cancer cases; the painless nature is particularly significant as it may be falsely reassuring. Any single episode of painless visible haematuria in an adult mandates urgent urological investigation (2-week wait cancer referral in UK). Intermittent haematuria is typical — one episode may clear for weeks or months before recurring. Haematuria severity does not correlate with tumour stage. Irritative lower urinary tract symptoms (LUTS): urgency, frequency, and dysuria (painful urination) — particularly associated with carcinoma in situ (CIS); these symptoms may be attributed to UTI without haematuria and should not be assumed to be infective without culture. Recurrent 'UTI' not resolving with antibiotics: consider urothelial malignancy or carcinoma in situ. Advanced disease symptoms: pelvic pain or suprapubic pain, flank pain from ureteric obstruction (hydronephrosis), lower limb oedema (lymphatic obstruction), palpable suprapubic mass, bone pain (metastases), weight loss, and fatigue.

Urine dipstick and microscopy: haematuria confirmed; urine culture to exclude UTI (but haematuria in the presence of UTI still requires full investigation in at-risk patients). Urine cytology: detects exfoliated malignant cells — high specificity, moderate sensitivity; sensitivity is highest for high-grade and carcinoma in situ. Flexible cystoscopy (in clinic under local anaesthesia): direct visualisation of the bladder mucosa — the gold standard diagnostic investigation; identifies tumours, their location, number, and gross morphology; allows biopsy. CT urogram (CTU): gold standard upper tract imaging — defines the bladder tumour (size, wall thickening, extravesical extension), detects upper tract urothelial tumours (renal pelvis, ureter), lymphadenopathy, and liver/lung metastases. CT chest/abdomen/pelvis staging: for muscle-invasive disease — identifies lymph node and distant metastases. MRI pelvis (mpMRI — multiparametric): superior to CT for assessing depth of muscle invasion (T staging) — differentiates superficial NMIBC from MIBC; used for staging in muscle-invasive disease and guiding surgery. TURBT (transurethral resection of bladder tumour): the definitive diagnostic and therapeutic procedure for NMIBC — performed under general or spinal anaesthesia; resects visible tumour and provides histological diagnosis including depth of invasion. Photodynamic cystoscopy (blue-light cystoscopy — Hexvix): instilled fluorescent drug (hexaminolevulinate) makes tumours fluoresce pink under blue light — detects flat CIS lesions missed by white-light cystoscopy; used at TURBT. Bone scan: if bone metastases suspected from symptoms or raised ALP.

Non-muscle-invasive bladder cancer (NMIBC — pTa, pT1, CIS): Initial treatment — TURBT (complete resection of all visible tumour and deep muscle biopsy to confirm non-invasion); repeat TURBT at 4-6 weeks if high-grade T1 tumour or incomplete initial resection. Adjuvant intravesical therapy: single instillation of intravesical mitomycin C immediately after TURBT (reduces risk of early tumour recurrence by 40%); intravesical BCG (Bacillus Calmette-Guerin — live attenuated mycobacterium) immunotherapy — standard of care for high-risk NMIBC (high-grade T1, CIS) — one induction course (6 weekly instillations) + maintenance (3-weekly instillations at 3, 6, 12, 18, 24, 30, 36 months); reduces recurrence and progression to MIBC; mechanism involves local innate and adaptive immune activation; side effects include dysuria, frequency, and rarely systemic BCG sepsis. Radical cystectomy is offered for very high-risk NMIBC (BCG-unresponsive CIS, multiple recurrences). Cystoscopic surveillance: lifelong surveillance cystoscopy every 3-12 months depending on risk group. Muscle-invasive bladder cancer (MIBC — pT2 and above): Radical cystectomy (removal of bladder, prostate/seminal vesicles in men, or uterus/anterior vagina/ovaries in women; urinary diversion — ileal conduit or orthotopic neobladder) — the standard curative treatment; neoadjuvant cisplatin-based chemotherapy (MVAC or GC — gemcitabine-cisplatin — given before surgery; improves 5-year survival by 5-8% and pathological complete response); neoadjuvant immunotherapy + chemotherapy combinations under investigation. Radical radiotherapy with concurrent radiosensitising chemotherapy (cisplatin, 5-fluorouracil + mitomycin C): bladder-preserving curative option for medically unfit patients or those wishing to avoid cystectomy; similar 5-year survival to cystectomy in selected patients (BCON trial). Metastatic bladder cancer: first-line cisplatin-eligible: cisplatin + gemcitabine (GC); switch maintenance avelumab (PD-L1 inhibitor) after response improves overall survival (JAVELIN Bladder 100 trial). Cisplatin-ineligible: pembrolizumab or atezolizumab (PD-1/PD-L1 checkpoint inhibitors) for PD-L1-positive tumours. Second-line: pembrolizumab (KEYNOTE-045); erdafitinib (FGFR2/3 inhibitor for FGFR-altered tumours); enfortumab vedotin (antibody-drug conjugate targeting Nectin-4); sacituzumab govitecan.

Haematuria-related anaemia (severe chronic haematuria from large tumours or after incomplete TURBT can cause profound iron-deficiency anaemia requiring transfusion and urgent haemostatic TURBT). Ureteric obstruction (locally advanced bladder cancer obstructs both ureters — bilateral hydronephrosis and acute renal failure — requiring emergency ureteric stenting or percutaneous nephrostomy). Metastatic disease (bladder cancer metastasises most commonly to pelvic lymph nodes, liver, lung, and bone — bone metastases cause severe pain, pathological fractures, and hypercalcaemia). BCG sepsis (systemic BCG-osis — prolonged fever above 38.5°C, rigors, and systemic illness after intravesical BCG; requires immediate cessation of BCG and treatment with isoniazid plus rifampicin for at least 6 months). Radical cystectomy complications (urinary diversion problems with ileal conduit; neobladder night-time incontinence and voiding dysfunction; erectile dysfunction in 60-80% of men post-cystectomy; metabolic complications from the intestinal segment used for diversion). High recurrence rate (NMIBC recurs in 50-70% of patients at 5 years — without BCG treatment and lifelong cystoscopic surveillance, progression to muscle-invasive and metastatic disease is common).

Stop smoking: the single most impactful intervention — smoking cessation reduces bladder cancer risk, though the elevated risk never fully returns to baseline. People who have smoked for 40 years or above retain approximately double the risk of non-smokers even after cessation, but risk declines progressively with time since quitting. Occupational protection: industries with aromatic amine exposure (rubber manufacturing, dye production, leather work) must implement chemical substitution, enclosed processes, personal protective equipment, and regular medical surveillance with urine cytology for exposed workers. Adequate hydration: increases urinary flow and reduces carcinogen contact time with the urothelium — some epidemiological evidence for reduced bladder cancer risk with high fluid intake. Schistosoma haematobium prevention: avoid freshwater swimming in endemic areas (sub-Saharan Africa, Nile delta — schistosomiasis causes squamous cell carcinoma of the bladder); praziquantel treatment for established infection. Lifelong cystoscopic surveillance for all patients with previous bladder cancer — recurrence is the rule rather than the exception in NMIBC (50-70% recurrence at 5 years); early detection of recurrence allows repeat TURBT before progression to muscle-invasive disease.

Seek urgent GP assessment — same day or next day — for any episode of visible blood in the urine (macroscopic haematuria), even if pain-free, even if it has resolved. A single episode of painless haematuria in an adult over 45 warrants 2-week wait (urgent suspected cancer pathway) urology referral in UK practice. Do not assume it is due to a UTI without full investigation. Go to A&E immediately for: haematuria with clots causing inability to pass urine (clot retention), severe haematuria with signs of haemodynamic compromise (dizziness, rapid pulse), or fever with rigors (urosepsis). During treatment and surveillance: contact your urology team urgently for: symptoms of BCG infection (prolonged fever above 38.5°C for more than 48 hours after BCG instillation, rigors, malaise — requires systemic antituberculous therapy), any new haematuria between surveillance cystoscopies, flank pain suggesting ureteric obstruction, or any new systemic symptoms (bone pain, significant weight loss, breathlessness) suggesting disease progression.