What is the treatment for transitional bladder cancer?

Treatment of Transitional Bladder Cancer

Treatment of transitional cell carcinoma of the bladder is determined by stage and risk stratification: non-muscle invasive disease (Ta, T1, CIS) requires transurethral resection followed by intravesical BCG therapy for high-risk tumors, while muscle-invasive disease (T2-T3) mandates radical cystectomy with neoadjuvant platinum-based chemotherapy, and metastatic disease requires systemic platinum-based combination chemotherapy. 1, 2

Initial Diagnostic Approach

• Transurethral resection (TUR/TURBT) with biopsy is the cornerstone of diagnosis and initial treatment, providing histopathological confirmation and staging information 1, 2
• Perform bimanual examination under anesthesia at the time of TUR to assess for palpable mass and extravesical extension 3, 2
• Ensure muscle tissue is present in the pathological specimen for accurate staging—when absent, the tumor must be staged as Tx 4
• Complete staging workup includes: blood counts, creatinine, chest imaging, CT scan of abdomen/pelvis, and urine cytology 3

Treatment Algorithm by Stage

Non-Muscle Invasive Disease (Stage Ta, T1, CIS)

Low-Risk Tumors (Small, Low-Grade Ta)

• Complete TUR followed by single immediate intravesical chemotherapy instillation within 24 hours reduces recurrence risk by 40% 3, 1
• Single-dose mitomycin C immediately postoperatively is recommended for papillary Ta tumors without bladder perforation 2, 5
• Follow with cystoscopy at 3 months, then at increasing intervals as appropriate 1

High-Risk Tumors (T1, High-Grade, Multifocal, or CIS)

• Intravesical BCG therapy after complete TUR is the standard treatment and most effective conservative approach 3, 1, 6
• BCG prevents recurrences and reduces mortality by 23% with high-level evidence 1
• Full-dose BCG with 3-year maintenance is superior to reduced doses or shorter duration—1/3 dose or one-year full dose are suboptimal 4
• At 3-6 months, lack of complete response to BCG is a significant predictor for progression and warrants consideration of cystectomy 4, 5

When to Proceed Directly to Radical Cystectomy

Immediate radical cystectomy should be considered for: 4, 5

• High-grade, multiple T1 tumors
• T1 tumors at sites difficult to resect
• Residual T1 tumors after resection
• High-grade tumors with CIS and lymphovascular invasion
• Prostatic duct or stromal involvement
• Young patients with high-grade T1 plus additional poor prognostic factors (multifocality, associated CIS)

Critical caveat: Postponing radical cystectomy until progression to muscle-invasive disease may negatively impact survival 4

Muscle-Invasive Disease (Stage T2-T3)

• Radical cystectomy with extended bilateral pelvic lymphadenectomy is the standard treatment 3, 1, 2
• Neoadjuvant cisplatin-based combination chemotherapy before cystectomy provides a 5% survival benefit at 5 years 3, 1
• Two large randomized trials and meta-analysis support platinum-based combination chemotherapy (MVAC or gemcitabine-cisplatin) before radical cystectomy or definitive radiotherapy 3

Alternative Bladder-Preservation Approaches

• Trimodality therapy (complete TUR with radiotherapy ± concurrent chemotherapy) is a reasonable alternative for: 3, 1
  • Patients medically unfit for surgery
  • Initial T2 tumors <5 cm without CIS
  • Patients with good performance status who seek alternatives
• Segmental (partial) cystectomy may be considered for solitary lesions in amenable locations with adequate margins, no CIS, and no history of multifocal disease 1, 2

Advanced/Metastatic Disease (Stage IV)

• Platinum-based combination chemotherapy is first-line treatment: either MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) or gemcitabine-cisplatin 1, 2, 7
• Cisplatin is indicated as a single agent for transitional cell bladder cancer no longer amenable to local treatments 7
• For patients progressing on first-line platinum-based chemotherapy, palliative radiotherapy may reduce symptoms 3

Follow-Up Protocols

After Bladder-Preservation Strategy

• Cystoscopy and urinary cytology every 3 months during the first 2 years, then every 6 months thereafter 3, 1
• Consider imaging of upper tract every 1-2 years for high-grade tumors 1

After Radical Cystectomy

• Clinical control every 3 months during the first 2 years, then every 6 months for 5 years 3
• Urine cytology, creatinine, and electrolytes every 3-6 months for 2 years, then as clinically indicated 1
• Imaging of chest, abdomen, and pelvis every 3-12 months for 2 years based on recurrence risk 1

Important Caveats and Pitfalls

• Repeat TUR is mandatory when no muscle is present in the specimen for high-grade disease, any T1 lesion, or inadequate staging from first resection—this reduces tumor left behind and improves staging 1, 4
• BCG failure at 3 months requires aggressive reassessment; continuing ineffective intravesical therapy delays potentially curative cystectomy 4, 5
• Cisplatin produces cumulative nephrotoxicity and should not be given more frequently than once every 3-4 weeks; monitor renal function, electrolytes, and magnesium levels before each course 7
• Cisplatin causes cumulative ototoxicity—audiometric testing is required prior to initiating therapy and before each subsequent dose 7
• Pure squamous cell carcinomas and adenocarcinomas should be treated as invasive bladder tumors, but systemic chemotherapy regimens for transitional cell carcinomas are generally ineffective for these histologies 2