Key Facts

Bladder cancer is a common urological malignancy with significant morbidity and mortality. Early detection through prompt investigation of haematuria is crucial. Non-muscle-invasive disease requires long-term surveillance due to high recurrence rates.

Epidemiology

Approximately 10,000 new cases per year in the UK. Male-to-female ratio is approximately 3:1. Fourth most common cancer in men. Median age at diagnosis is approximately 73 years. The UK has one of the highest incidence rates in Europe.

Aetiology

• Smoking: Most important risk factor — responsible for ~50% of cases
• Occupational exposure: Aromatic amines, polycyclic aromatic hydrocarbons — rubber, dye, textile industries (latency 15-40 years)
• Schistosoma haematobium: Squamous cell carcinoma of the bladder (endemic areas)
• Cyclophosphamide/ifosfamide: Chemical cystitis and increased TCC risk
• Pelvic radiotherapy: Increased risk
• Chronic catheterisation/stones: SCC risk

Pathophysiology

The majority of bladder cancers are urothelial (transitional cell) carcinomas arising from the urothelium. Two distinct pathways:

1. Papillary pathway: Low-grade Ta tumours — FGFR3 mutations, high recurrence but low progression
2. CIS pathway: Flat high-grade dysplasia → muscle-invasive cancer — p53 mutations, high progression risk

Muscle-invasive disease invades the detrusor muscle and may spread to perivesical fat, adjacent organs, lymph nodes, and distant sites (lung, bone, liver).

Typical Presentation

• Painless visible haematuria: Present in ~80% — the classic presenting feature
• Recurrent UTIs (especially in non-response to antibiotics)
• Storage LUTS: Frequency, urgency, dysuria

Advanced Disease

• Pelvic pain, weight loss, anorexia
• Palpable suprapubic mass
• Hydronephrosis (ureteric orifice involvement)
• Lower limb oedema (pelvic lymph node involvement)

CIS (Carcinoma in Situ)

• Irritative LUTS: Frequency, urgency, dysuria
• May have no visible haematuria
• Often multifocal, flat, high-grade — aggressive behaviour

Red Flags

• Visible haematuria (any age) — urgent 2WW referral
• Non-visible haematuria aged ≥60 — investigate
• Recurrent UTIs in a non-typical patient (male, elderly) — investigate for underlying pathology
• LUTS with positive urine cytology — consider CIS

Bedside

• Urine dipstick: Haematuria
• MSU: Exclude UTI
• Urine cytology: Sensitivity 30-70% (better for high-grade/CIS); high specificity

Bloods

• FBC: Anaemia from chronic haematuria
• U&Es: Renal function — obstruction
• LFTs: Liver metastases

Imaging

• CT urogram: Standard imaging for haematuria investigation — detects upper tract lesions and bladder masses
• Flexible cystoscopy: Gold standard for detecting bladder tumours
• CT chest/abdomen/pelvis: Staging for MIBC
• MRI pelvis: Local staging of MIBC (VI-RADS scoring)
• PET-CT: Increasingly used for nodal/metastatic staging

Special Tests

• TURBT: Diagnostic (histological grading/staging) and therapeutic; must include detrusor muscle in specimen
• Re-TURBT: Recommended 2-6 weeks after initial TURBT for T1 or high-grade tumours (upstaging in ~25%)
• Blue light/NBI cystoscopy: Enhanced detection of CIS and flat tumours
• Urine biomarkers: NMP22, BTA stat — not routinely recommended by NICE

Non-pharmacological

• Smoking cessation: Most important lifestyle intervention; reduces recurrence
• Occupational health: Report to IIDB (Industrial Injuries Disablement Benefit) if occupational bladder cancer

Pharmacological

• Intravesical mitomycin C: Single instillation within 24 hours of TURBT for low/intermediate-risk NMIBC (reduces recurrence by ~40%)
• Intravesical BCG (Bacillus Calmette-Guérin): Induction (6 weekly instillations) + maintenance (3 weekly at 3, 6, 12 months) — for high-risk NMIBC and CIS (SWOG 8507 protocol)
• Neoadjuvant cisplatin-based chemotherapy: GC (gemcitabine + cisplatin) or accelerated MVAC before radical cystectomy for MIBC (NICE NG2)
• Pembrolizumab/atezolizumab: Immune checkpoint inhibitors for metastatic/cisplatin-ineligible patients

Surgical/Interventional

• TURBT: Initial treatment for all bladder tumours — diagnostic and therapeutic
• Radical cystectomy: Standard for MIBC — includes pelvic lymph node dissection
• Urinary diversion: Ileal conduit (most common), continent diversion (Mitrofanoff), or orthotopic neobladder
• Radical radiotherapy: Alternative to cystectomy for MIBC (bladder preservation) — often with concurrent chemotherapy (mitomycin + 5-FU, BC2001 trial)
• Trimodal therapy: TURBT + chemoradiation — bladder-sparing approach

Referral Criteria

• Visible haematuria — urgent 2WW referral to urology
• Non-visible haematuria aged ≥60 — urology referral
• Confirmed bladder cancer — MDT discussion
• NMIBC refractory to BCG — consider cystectomy

• NMIBC: 5-year survival >85%; recurrence rate 50-70% for Ta tumours; progression to MIBC in 10-15% of T1 high-grade
• MIBC (T2-T4): 5-year survival 40-50% after radical cystectomy with neoadjuvant chemotherapy
• Metastatic: Median survival 12-18 months with chemotherapy; improved with immunotherapy
• CIS: Without treatment, ~50% progress to MIBC within 5 years; BCG achieves complete response in 70-80%
• Radical cystectomy mortality: 2-5% at 90 days in specialist centres

TNM Staging of Bladder Cancer

Risk Stratification of NMIBC

Landmark Trials