What is the recommended management for recurrent non-muscle invasive bladder tumor?

Management of Recurrent Non-Muscle Invasive Bladder Tumors

For recurrent non-muscle invasive bladder cancer (NMIBC), the recommended management depends on risk stratification, previous treatments, and response patterns, with BCG immunotherapy being the preferred treatment for high-risk recurrences and radical cystectomy indicated for BCG-unresponsive disease.

Initial Evaluation

• Complete transurethral resection of bladder tumor (TURBT) is essential for all patients with recurrent NMIBC 1
• For T1 disease, repeat TURBT of the primary tumor site including muscularis propria should be performed within six weeks of initial TURBT to ensure complete resection and accurate staging 1
• For high-grade Ta tumors without muscle in the specimen, repeat TURBT should be considered, especially with large or multifocal tumors 1

Risk-Based Management Approach

Low-Risk Recurrence

• For patients with recurrent low-risk tumors after intravesical chemotherapy, a single immediate instillation of intravesical chemotherapy can be given 1
• For recurrent low-risk tumors after BCG immunotherapy, continued intravesical BCG immunotherapy can be considered 1
• Follow-up should include cystoscopy at 3 months, at 12 months, and then annually for at least 5 years 1

Intermediate-Risk Recurrence

• After complete TURBT, options include:
  • BCG induction (6 weekly instillations) plus maintenance for one year 1
  • Intravesical chemotherapy (not exceeding 12 months of treatment) 1
• For recurrence after chemotherapy, switch to BCG induction plus maintenance 1
• For recurrence after BCG, consider repeat BCG induction plus maintenance or radical cystectomy depending on the extent and timing of recurrence 1
• Follow-up should include cystoscopy and urine cytology every 3 months for the first year, then at increasing intervals 1

High-Risk Recurrence

• For high-risk recurrent NMIBC, BCG induction (6 weekly instillations) followed by maintenance for three years is strongly recommended as the primary treatment option 1
• For persistent or recurrent high-grade disease within 6 months of two induction courses of BCG or induction plus maintenance, additional BCG should not be given 1
• For high-grade recurrence in high-risk patients, radical cystectomy is preferred 1
• For patients unfit or unwilling to undergo cystectomy, alternative intravesical therapies may be considered 1

BCG Failure Management

• BCG failure can be categorized as BCG-refractory (no response to BCG), BCG-relapsing (recurrence after initial response), or BCG-intolerant (unable to complete treatment due to adverse effects) 1
• For high-risk patients with persistent or recurrent disease within one year following treatment with two induction cycles of BCG or BCG maintenance, radical cystectomy should be offered 1
• For intermediate-risk patients with BCG failure, options include repeat BCG induction plus maintenance or radical cystectomy 1
• For patients with T1 disease recurrence after BCG, cystectomy is recommended 1

Specific Scenarios

• For persistent high-grade T1 disease on repeat resection, T1 tumors with lymphovascular invasion, or variant histologies, consider offering initial radical cystectomy 1
• For high-grade T1 disease after a single course of induction intravesical BCG, radical cystectomy should be offered 1
• For CIS recurrence, a second course of BCG may be given, but if residual disease persists at the second 12-week follow-up, cystectomy should be strongly considered 1

Maintenance BCG Protocol

• The optimal maintenance schedule is based on the Southwest Oncology Group regimen: 3 weekly instillations at 3 and 6 months after induction, and every 6 months thereafter for up to 3 years 1
• For high-risk patients who completely respond to induction BCG, maintenance BCG should be continued for three years, as tolerated 1
• For intermediate-risk patients who completely respond to induction BCG, maintenance BCG for one year should be considered 1

Follow-up Schedule

• For high-risk disease: cystoscopy and cytology every 3 months for 2 years, every 4 months in the third year, every 6 months until 5 years, and annually thereafter 1
• Annual upper urinary tract imaging should be considered for high-risk tumors 1
• For intermediate-risk disease: follow-up schedule should be between that for low and high-risk disease 1

Important Considerations

• Early cystectomy has been shown to improve long-term survival in high-risk patients with BCG failure compared to delayed cystectomy 1
• Deferring cystectomy until progression to muscle-invasive disease may negatively impact survival 1
• Incomplete resection is a significant factor in early recurrences, with tumors noted at first follow-up cystoscopy in up to 45% of patients 1
• BCG with maintenance has been shown to be superior to mitomycin C in preventing recurrence in intermediate and high-risk patients 1