What is the next step in treatment for a 60-year-old man with Carcinoma In Situ (CIS) of the bladder who has completed an induction course of Bacillus Calmette-Guérin (BCG) therapy, has no residual tumor on follow-up biopsy, and shows mild atypia on cytology?

Management of CIS of the Bladder After BCG Induction with Complete Response

For a 60-year-old man with CIS of the bladder who has completed an induction course of BCG with no residual tumor on follow-up biopsy and only mild atypia on cytology, the next step should be maintenance BCG therapy consisting of three weekly instillations at 3 and 6 months, then every 6 months for two years. 1

Rationale for Maintenance BCG Therapy

The European Society for Medical Oncology (ESMO) guidelines strongly recommend maintenance BCG therapy for high-risk non-muscle invasive bladder cancer (NMIBC) patients, including those with CIS, who have responded to induction therapy 2, 1. This recommendation carries the highest level of evidence [I, A].

The maintenance schedule should follow this pattern:

• Three weekly instillations at months 3,6, and 12 after induction
• Continue with three weekly instillations at months 18,24,30, and 36 2

For high-risk NMIBC (which includes CIS), full-dose intravesical BCG for 1-3 years is recommended, with three-year maintenance being more effective than one year for preventing recurrences 2.

Why Maintenance Therapy is Necessary

Despite the patient showing no residual tumor on follow-up biopsy, maintenance therapy is critical because:

1. CIS is considered high-risk NMIBC with significant potential for recurrence and progression
2. The presence of mild atypia on cytology suggests potential ongoing cellular changes that require monitoring
3. Long-term studies show that without maintenance therapy, the 5-year disease-free rate in complete responders drops to approximately 60% 3

Proper Maintenance Protocol

The FDA-approved administration protocol for BCG maintenance includes:

• Intravesical instillation retained for 2 hours if possible
• Patient repositioning every 15 minutes during retention to maximize bladder surface exposure 4
• Full-dose BCG is recommended, though dose reduction may be considered if patients cannot tolerate it 1

Surveillance During Maintenance Therapy

During the maintenance therapy period, regular surveillance is essential:

• Cystoscopy and urinary cytology every 3 months for the first 2 years
• Then every 6 months for years 3-4
• Annually thereafter 1
• Upper tract imaging at least once within the first 2 years 1

Common Pitfalls to Avoid

1. Inadequate follow-up: Failing to adhere to the recommended surveillance schedule increases the risk of missing recurrence
2. Premature termination of maintenance: Studies show that complete responders still have a significant risk of recurrence without adequate maintenance therapy 3
3. Ignoring side effects: Drug cystitis (45%), bacterial cystitis (15%), and fever (15%) are common side effects that need monitoring 3
4. Missing signs of BCG failure: Be vigilant for BCG-refractory, BCG-relapsing, or BCG-unresponsive disease 1

Alternative Options and Why They Are Not Optimal

• Cystoscopy and cytology in three months without maintenance BCG: Insufficient for high-risk disease like CIS, which requires maintenance therapy to prevent recurrence 2, 1
• Monthly BCG for one year: More intensive than the evidence-based schedule and may increase toxicity without additional benefit
• Intravesical mitomycin C: Generally reserved for BCG-intolerant patients or as an alternative when BCG fails 2, 1
• Additional six weeks of BCG: Not indicated when there is complete response to induction; maintenance schedule is more appropriate 1

The evidence clearly supports maintenance BCG therapy with the schedule of three weekly instillations at 3 and 6 months, then every 6 months for two years, as the optimal next step for this patient with CIS who has responded to induction BCG therapy.