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Bladder Cancer

Basics

  • Primary malignancy of the urinary bladder lining
  • Cell types:
  • Urothelial carcinoma (>90% in USA/Europe)
  • Squamous cell carcinoma
  • Adenocarcinoma
  • Classification based on invasion:
  • Nonmuscle invasive bladder cancer (NMIBC)
  • Muscle invasive bladder cancer (MIBC)
  • Metastatic disease

Epidemiology

  • Predominantly white men >55 years old
  • Incidence: ~4.2% of all new cancers in 2023
  • Median diagnosis age: 73 years
  • Male:female ratio 3-4:1, equal risk in smokers
  • Fourth most common cancer in men (US)
  • Lifetime risk: men 1 in 28, women 1 in 91

Etiology and Pathophysiology

  • Unknown exact cause; strong relation to risk factors
  • 70% present as nonmuscle invasive, better survival
  • 30% muscle invasive at diagnosis, worse prognosis
  • Genetics:
  • Lynch syndrome increases risk (up to 20%) due to DNA repair defects

Risk Factors

  • Male sex
  • Older age (longer carcinogen exposure)
  • Tobacco smoking (50% of cases)
  • Occupational exposure (benzidine dyes, rubber, petroleum, arsenic)
  • History of bladder radiation or chemotherapy (cyclophosphamide)
  • Chronic urinary tract infections or catheters
  • Drugs: pioglitazone, aristolochic acid

Alert: Microscopic or gross hematuria in a smoker requires cystoscopy and upper tract imaging regardless of anticoagulation status unless explained by UTI or benign cause.

Prevention

  • Tobacco cessation programs
  • Avoid or limit occupational carcinogen exposure
  • Prompt evaluation of hematuria

Diagnosis

History

  • Painless hematuria (most common symptom)
  • Irritative urinary symptoms (frequency, urgency, dysuria)
  • Occupational or radiation exposure
  • Abdominal/pelvic pain in advanced disease
  • Chronic indwelling catheter use

Physical Exam

  • Usually normal early
  • Palpable abdominal or pelvic mass in advanced disease

Differential Diagnosis

  • UTI, nephrolithiasis
  • Hemorrhagic cystitis
  • Urinary tract trauma
  • Renal cell carcinoma
  • Interstitial cystitis/nephritis

Tests and Imaging

  • Urinalysis with microscopy for hematuria
  • Cystoscopy for all with hematuria (except low-risk asymptomatic microhematuria with shared decision-making)
  • Upper tract imaging: CT/MRI urography, renal ultrasound (low/intermediate risk)
  • Transurethral resection of bladder tumor (TURBT) for diagnosis and staging
  • Urine cytology (high specificity, low sensitivity)
  • Enhanced cystoscopy (blue light, narrowband) improves detection
  • MRI with VI-RADS scoring for muscle invasion estimation

Staging (TNM simplified)

  • Ta: Noninvasive papillary (low grade)
  • Tis: Carcinoma in situ (CIS), high grade
  • T1: Invades submucosa/lamina propria
  • T2: Invades muscle (superficial or deep)
  • T3: Invades perivesical fat
  • T4: Invades adjacent organs
  • N1-N3: Lymph node involvement
  • M: Distant metastasis

Treatment

NMIBC

  • Low risk (solitary Ta ≤3 cm): TURBT + single-dose intravesical chemo (<24h), no maintenance
  • Intermediate risk: TURBT + restage TURBT (T1), induction intravesical chemo or BCG + maintenance (1 year)
  • High risk (T1 high grade, CIS, multiple/recurrent): TURBT + induction + maintenance BCG (3 years), consider radical cystectomy if refractory or variant histology

MIBC (nonmetastatic)

  • Cisplatin eligible: Neoadjuvant cisplatin-based chemo + radical cystectomy or chemoradiation
  • Cisplatin ineligible: Radical cystectomy or chemoradiation; partial cystectomy or maximal TURBT alternative

Metastatic MIBC

  • Cisplatin eligible: Chemo (gemcitabine + cisplatin or ddMVAC)
  • Cisplatin ineligible or PD-L1 positive: Immunotherapy (atezolizumab, pembrolizumab)
  • Postplatinum failure: Immunotherapy or targeted therapies (enfortumab vedotin, erdafitinib)

Medications

  • Refer to above treatment algorithms for chemo and immunotherapy agents

Referral

  • Early referral for hematuria evaluation
  • Urologic oncology for management of invasive or recurrent disease

Surgery

  • TURBT for diagnosis and initial management of superficial tumors
  • Radical cystectomy with lymphadenectomy for invasive disease
  • Urinary diversion after cystectomy

Follow-Up

  • NMIBC low risk: Cystoscopy 3-4 months, 6-9 months, then yearly for 5 years
  • NMIBC intermediate/high risk: Cystoscopy + cytology every 3-6 months initially, then yearly; upper tract imaging every 1-2 years
  • MIBC: Imaging (chest x-ray, PET), labs for metastatic surveillance

Patient Education

  • Smoking cessation
  • Awareness of hematuria and prompt evaluation
  • Occupational exposure precautions

Prognosis

  • 5-year relapse-free survival: low risk 43%, intermediate 33%, high 23%
  • 5-year progression-free survival: low risk 93%, intermediate 74%, high 54%
  • MIBC nonmetastatic 36-48% 5-year overall survival
  • Metastatic disease 5-year survival: regional 36%, distant 5%

Complications

  • Azotemia and metabolic acidosis in neobladder patients
  • Recurrence and progression