Overview
Bladder Cancer
1. Clinical Overview
Summary
Bladder cancer is the most common malignancy of the urinary tract and the 10th most common cancer worldwide. The vast majority (90%) are urothelial (transitional cell) carcinomas arising from the bladder urothelium. The cardinal presenting symptom is painless visible haematuria. Smoking is the dominant risk factor, contributing to 50% of cases. Bladder cancer is broadly classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), with treatment and prognosis differing substantially between the two. NMIBC is managed with transurethral resection and intravesical therapy (BCG or chemotherapy), while MIBC requires radical cystectomy with neoadjuvant chemotherapy or bladder-preserving chemoradiotherapy.
Key Facts
- Incidence: 10th most common cancer; ~10,000 cases/year (UK)
- Sex ratio: Male:Female = 3:1
- Peak age: 65-74 years
- Histology: 90% urothelial (TCC); 5% squamous; 2% adenocarcinoma
- Main risk factor: Smoking (50% of cases)
- Cardinal symptom: Painless visible haematuria
Clinical Pearls
Haematuria = Cancer Until Proven Otherwise: Any adult with visible haematuria requires urgent urology referral and cystoscopy. Even a single episode matters.
Smoking Is Half the Story: Smoking causes 50% of bladder cancers. Occupational exposures (dyes, rubber, aromatic amines) account for another significant proportion.
BCG Is Immunotherapy: Intravesical BCG for high-risk NMIBC is one of the oldest forms of immunotherapy — and still highly effective.
Why This Matters Clinically
Bladder cancer is common, highly treatable if caught early, but often recurs. NMIBC requires lifelong surveillance. MIBC requires aggressive multimodal treatment. Early diagnosis from haematuria investigation saves lives.
2. Epidemiology
Incidence & Prevalence
- Incidence: ~10,000 new cases/year (UK); 570,000 worldwide
- Mortality: ~5,000 deaths/year (UK)
- Rank: 10th most common cancer globally
Demographics
| Factor | Details |
|---|---|
| Age | Median age at diagnosis: 73 years |
| Sex | Male:Female = 3:1 |
| Ethnicity | Higher in White populations |
| Geography | Higher in industrialised countries |
Risk Factors
| Factor | Impact |
|---|---|
| Smoking | 50% attributable risk; dose-dependent |
| Occupational exposure | Aromatic amines, dyes, rubber, printing |
| Schistosomiasis | Squamous cell carcinoma (endemic areas) |
| Chronic irritation | Indwelling catheters, stones |
| Cyclophosphamide | Haemorrhagic cystitis, SCC |
| Pelvic radiation | Previous radiotherapy |
| Family history | Modest increase |
3. Pathophysiology
Histology
| Type | Frequency | Notes |
|---|---|---|
| Urothelial (TCC) | 90% | Most common; arises from urothelium |
| Squamous cell carcinoma | 5% | Associated with schistosomiasis, chronic irritation |
| Adenocarcinoma | 2% | Urachal remnant, cystitis glandularis |
| Small cell | Rare | Aggressive; neuroendocrine |
Staging (TNM)
T Stage:
| Stage | Description |
|---|---|
| Ta | Non-invasive papillary |
| Tis | Carcinoma in situ (CIS) — flat, high-grade |
| T1 | Invades lamina propria |
| T2 | Invades muscularis propria (muscle-invasive) |
| T3 | Invades perivesical fat |
| T4 | Invades adjacent organs (prostate, uterus, pelvic wall) |
Classification:
| Category | Stages | Treatment Focus |
|---|---|---|
| NMIBC | Ta, Tis, T1 | TURBT ± intravesical therapy |
| MIBC | ≥T2 | Radical cystectomy or chemoradiotherapy |
| Metastatic | Any T, N+, M1 | Systemic therapy |
Risk Stratification (NMIBC)
| Risk Group | Features |
|---|---|
| Low | Single Ta, low-grade, less than 3cm, no CIS |
| Intermediate | Recurrent Ta low-grade; multiple tumours |
| High | T1, high-grade, CIS, large, recurrent |
4. Clinical Presentation
Symptoms
| Symptom | Frequency | Notes |
|---|---|---|
| Visible (gross) haematuria | 80-90% | Painless; intermittent |
| Microscopic haematuria | Variable | Often incidental finding |
| Dysuria | 20% | Especially with CIS |
| Frequency/urgency | 20% | Irritative symptoms |
| Recurrent UTI | Variable | Especially in older adults |
| Pelvic pain | Late | Advanced disease |
| Weight loss, anorexia | Late | Metastatic disease |
Signs
Red Flags
[!CAUTION] Red Flags — Urgent referral if:
- Visible haematuria (any age)
- Non-visible haematuria with age ≥60 (refer)
- Recurrent UTIs with risk factors
- Unexplained lower urinary tract symptoms
- Pelvic mass or hydronephrosis
Usually no physical signs in early disease
Common presentation.
Palpable pelvic mass (advanced)
Common presentation.
Suprapubic tenderness (rare)
Common presentation.
Anaemia (chronic haematuria, metastatic)
Common presentation.
5. Clinical Examination
Structured Approach
Abdominal:
- Palpable bladder (retention, large tumour)
- Suprapubic mass
- Flank mass (hydronephrosis)
DRE (in males):
- Assess for prostate abnormality
- Pelvic sidewall fixation (advanced bladder cancer)
General:
- Pallor (anaemia)
- Cachexia (metastatic)
- Lymphadenopathy (inguinal, supraclavicular)
6. Investigations
First-Line
| Test | Purpose |
|---|---|
| Urinalysis | Confirm haematuria; exclude infection |
| Urine cytology | High-grade tumours; CIS detection |
| Renal function (eGFR, U&Es) | Baseline; exclude obstruction |
| FBC | Anaemia |
Imaging
| Modality | Indication | Findings |
|---|---|---|
| CT urogram | Gold standard for haematuria work-up | Bladder mass, upper tract lesions, hydronephrosis |
| USS | If CT contraindicated | Bladder thickening, hydronephrosis |
| MRI pelvis | MIBC staging | Depth of invasion, nodes |
| CT chest/abdomen | Metastatic work-up | Lung, liver, nodes |
| PET-CT | Node-positive/metastatic | Staging |
Cystoscopy
- Flexible cystoscopy: Outpatient; visualise bladder; biopsy
- Rigid cystoscopy + TURBT: If tumour seen; diagnostic and therapeutic
Biopsy and Histology
- TURBT: Resect tumour + sample muscle layer
- Confirm invasiveness (muscle in specimen)
- Grade (low vs high)
7. Management
Management Algorithm
VISIBLE HAEMATURIA
↓
┌────────────────────────────────────────┐
│ 1. CT Urogram + Flexible Cystoscopy │
│ - Exclude upper tract pathology │
│ - Visualise bladder │
└────────────────────────────────────────┘
↓
┌────────────────────────────────────────┐
│ 2. If Tumour Seen → TURBT │
│ - Resect tumour │
│ - Sample detrusor muscle │
│ - Histological staging │
└────────────────────────────────────────┘
↓
┌─────────────────────┬──────────────────┐
│ NMIBC │ MIBC │
│ (Ta, Tis, T1) │ (≥T2) │
├─────────────────────┼──────────────────┤
│ - Risk stratify │ - Staging CT/MRI│
│ - Low: TURBT only │ - MDT decision │
│ - Intermediate: │ - Neoadjuvant │
│ Mitomycin C │ chemo + RC │
│ - High: BCG course │ OR │
│ - Surveillance │ - Chemoradio- │
│ cystoscopy │ therapy │
└─────────────────────┴──────────────────┘
NMIBC Management
| Risk | Treatment | Surveillance |
|---|---|---|
| Low | TURBT alone | Cystoscopy at 3, 12 months; then yearly |
| Intermediate | TURBT + single Mitomycin C (immediate) | Cystoscopy at 3, 6, 12 months; yearly |
| High | TURBT + BCG maintenance (3 years) | Intensive cystoscopy; upper tract surveillance |
BCG Therapy:
- Intravesical BCG weekly x6 (induction)
- Maintenance: 3-weekly courses at 3, 6, 12, 18, 24, 30, 36 months
- Side effects: Cystitis, haematuria; rare BCG sepsis
MIBC Management
| Option | Indication | Notes |
|---|---|---|
| Radical cystectomy | Standard of care | Ileal conduit or neobladder; ± neoadjuvant cisplatin-based chemo |
| Bladder-preserving chemoradiotherapy | If unfit or declines surgery | Trimodal therapy (TURBT + chemo + RT) |
| Neoadjuvant chemotherapy | Cisplatin-based (MVAC, GC) | Improves survival by 5-8% |
Metastatic Disease
| Treatment | Notes |
|---|---|
| Cisplatin-based chemotherapy | GC (gemcitabine + cisplatin) or MVAC |
| Carboplatin regimens | If cisplatin-ineligible |
| Checkpoint inhibitors | Pembrolizumab, atezolizumab (PD-1/PD-L1) |
| FGFR inhibitors | Erdafitinib (if FGFR alteration) |
| Enfortumab vedotin | Antibody-drug conjugate |
8. Complications
Disease-Related
| Complication | Details |
|---|---|
| Haematuria | May require cystoscopy/clot evacuation |
| Hydronephrosis | Ureteric obstruction |
| Renal failure | Bilateral obstruction |
| Metastases | Lung, liver, bone |
Treatment-Related
| Complication | Notes |
|---|---|
| BCG cystitis | Common; self-limiting |
| BCG sepsis | Rare; requires anti-TB therapy |
| Post-cystectomy morbidity | Ileus, anastomotic leak, metabolic acidosis |
| Sexual dysfunction | Post-cystectomy |
| Urinary diversion issues | Stomal problems, UTIs, stones |
9. Prognosis & Outcomes
5-Year Survival
| Stage | 5-Year Survival |
|---|---|
| Ta/T1 (NMIBC) | 90%+ |
| T2 (MIBC) | 60-70% |
| T3 | 35-50% |
| T4 / N+ | 10-20% |
| Metastatic | less than 10% |
Recurrence
- NMIBC recurrence: 50-70% at 5 years
- Progression to MIBC: 10-20% (high-risk NMIBC)
- Lifelong surveillance required
Prognostic Factors
| Good Prognosis | Poor Prognosis |
|---|---|
| Low-grade Ta | High-grade T1, CIS |
| Small, single tumour | Large, multiple, recurrent |
| Complete response to BCG | BCG failure |
| Organ-confined disease | Muscle invasion, nodes |
10. Evidence & Guidelines
Key Guidelines
- NICE NG2: Bladder cancer (2015, updated 2023) — UK pathway.
- EAU Guidelines on Non-muscle-invasive and Muscle-invasive Bladder Cancer — European Association of Urology.
- AUA Guidelines on Bladder Cancer — American Urological Association.
Landmark Trials
SWOG 8710 (2003) — Neoadjuvant chemotherapy before RC
- Key finding: Neoadjuvant MVAC improves survival in MIBC
- PMID: 12915604
KEYNOTE-045 (2017) — Pembrolizumab in advanced urothelial cancer
- Key finding: Pembrolizumab superior to chemotherapy after platinum failure
- PMID: 28212060
Evidence Strength
| Intervention | Level | Key Evidence |
|---|---|---|
| BCG for high-risk NMIBC | 1a | Multiple RCTs |
| Neoadjuvant chemo for MIBC | 1a | Meta-analyses |
| Radical cystectomy | 2a | Large series |
| Checkpoint inhibitors (advanced) | 1b | KEYNOTE-045 |
11. Patient/Layperson Explanation
What is Bladder Cancer?
Bladder cancer is when abnormal cells grow in the lining of your bladder (the organ that stores urine). The most common type is called urothelial or transitional cell carcinoma.
What causes it?
- Smoking is the biggest risk factor — causing half of all cases
- Some chemicals used in industry (dyes, rubber)
- Age (more common over 65)
What are the symptoms?
- Blood in your urine (often painless) — the most important warning sign
- Needing to urinate more often
- Pain when urinating
How is it treated?
- Non-muscle-invasive cancer: The tumour is removed through a telescope (TURBT). Medicine may be put into the bladder (BCG or chemotherapy) to stop it coming back.
- Muscle-invasive cancer: Surgery to remove the bladder (cystectomy), or a combination of chemotherapy and radiotherapy.
- Advanced cancer: Chemotherapy and immunotherapy.
What to expect
- Early bladder cancer has excellent survival rates
- It can come back, so regular check-ups (cystoscopies) are needed
- Removing the bladder means you will need a urostomy bag or a new bladder (neobladder)
When to see a doctor
See a doctor urgently if you notice blood in your urine — even once. Don't ignore it.
12. References
Primary Guidelines
- National Institute for Health and Care Excellence (NICE). Bladder cancer: diagnosis and management (NG2). 2015 (updated 2023). nice.org.uk/guidance/ng2
Key Trials
- Grossman HB, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer (SWOG 8710). N Engl J Med. 2003;349(9):859-66. PMID: 12915604
- Bellmunt J, et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma (KEYNOTE-045). N Engl J Med. 2017;376(11):1015-1026. PMID: 28212060
Further Resources
- Bladder Cancer UK: bladdercanceruk.org
- Macmillan Cancer Support: macmillan.org.uk
Last Reviewed: 2025-12-24 | MedVellum Editorial Team
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.