What is the recommended treatment for bladder carcinoma in situ (CIS)?

Treatment for Bladder Carcinoma In Situ (CIS)

For patients with bladder carcinoma in situ (CIS), intravesical BCG immunotherapy with induction followed by maintenance for 3 years is the recommended first-line treatment after transurethral resection of bladder tumor (TURBT). 1

Initial Management

1. Diagnosis and Staging:

   • Complete TURBT to remove all visible lesions
   • Ensure adequate tissue sampling for pathological confirmation
   • Use enhanced cystoscopy techniques (blue light/narrow band imaging) when available to improve CIS detection 2, 3

2. Risk Classification:

   • CIS is categorized as high-risk non-muscle invasive bladder cancer (NMIBC) 1
   • Requires aggressive management due to significant risk of recurrence and progression

First-Line Treatment

BCG Immunotherapy Protocol:

• Induction: 6 weekly instillations starting 2-3 weeks after TURBT 1
• Maintenance: Using SWOG schedule 1, 4
  • Three weekly instillations at months 3,6,12,18,24,30, and 36
  • Full 3-year maintenance recommended for optimal outcomes

Evidence Supporting BCG:

• Meta-analysis shows BCG significantly reduces 72-month recurrence rate (RR = 0.70) and 143-month recurrence rate (RR = 0.18) compared to intravesical chemotherapy 1
• BCG immunotherapy is superior to intravesical chemotherapy for CIS with strong evidence (level 1a-1b) 1
• Society for Immunotherapy of Cancer consensus strongly recommends BCG induction and maintenance for CIS 1

Management of BCG Response

Complete Response:

• Continue with maintenance schedule
• Regular surveillance with cystoscopy and cytology every 3 months for first 2 years, then every 6 months for years 3-4, and annually thereafter 4
• Upper tract imaging at least once in first 2 years, then every 1-2 years 4

BCG Failure Categories:

1. BCG-refractory: Persistent disease at 3 months after adequate induction 1
2. BCG-relapsing: Recurrence after achieving disease-free state at 6 months 1
3. BCG-unresponsive: Combination of BCG-refractory and BCG-relapsing within 6 months 1

Second-Line Options for BCG Failure

For BCG-unresponsive disease:

1. Radical Cystectomy (RC):

   • Recommended standard treatment for BCG-unresponsive CIS 1
   • Provides definitive treatment with highest cancer-specific survival

2. Alternative Options (for patients unfit or unwilling to undergo RC):

   • Pembrolizumab: Showed 41% complete response rate at 3 months with median duration of 16.2 months 1
   • Thermochemotherapy with mitomycin C: Can achieve 2-year disease-free survival in 47% of patients 1
   • BCG re-induction: May be considered in select cases 1

Common Pitfalls and Caveats

1. Inadequate Maintenance:

   • Skipping maintenance therapy significantly reduces treatment efficacy
   • Full 3-year maintenance schedule is associated with best outcomes 4, 5

2. Delayed Recognition of BCG Failure:

   • Delaying second-line therapy in non-responders increases risk of progression
   • Regular surveillance is critical to identify treatment failure early

3. Toxicity Management:

   • BCG-related side effects can lead to treatment discontinuation
   • Consider dose reduction (not treatment cessation) for significant local symptoms 4
   • Use of quinolones and/or anticholinergics can help manage side effects 4

4. Surveillance Errors:

   • Inadequate follow-up increases risk of missed recurrence
   • CIS can be difficult to detect visually - consider enhanced cystoscopy techniques 2, 3

Special Considerations

• For patients with CIS who undergo radical cystectomy, intravesical BCG is not required 1
• CIS with concurrent papillary tumors should be managed according to the highest risk component (CIS) 1
• Secondary CIS (occurring with other tumors) may have higher recurrence rates than primary CIS 6

By following this treatment algorithm, patients with bladder CIS can achieve optimal outcomes with reduced risk of recurrence, progression, and mortality.