What is the next step for a 60-year-old man with a single focus of Carcinoma In Situ (CIS) of the bladder, who has completed six doses of Bacillus Calmette-Guérin (BCG) therapy, with a normal cystoscopy and negative urinalysis one month after treatment?

Management of CIS of the Bladder After BCG Therapy: Next Steps

The next step for this 60-year-old man with a single focus of CIS of the bladder who has completed six doses of BCG with normal cystoscopy and negative cytology one month after treatment is to begin maintenance BCG therapy with 3 weekly instillations at 3,6, and 12 months for at least 1 year, with consideration for extending to 3 years. 1

Understanding the Current Situation

This patient has:

• High-risk non-muscle invasive bladder cancer (CIS)
• Completed induction BCG therapy (6 weekly doses)
• Normal cystoscopy and negative cytology at 1-month follow-up
• Appears to have had a complete response to initial treatment

Maintenance BCG Therapy Protocol

The ESMO guidelines clearly recommend maintenance BCG therapy for high-risk NMIBC patients (including those with CIS) who have responded to induction therapy 2:

• Schedule: 3 weekly instillations at months 3,6, and 12 after induction
• Duration: For high-risk patients like those with CIS, maintenance should continue for 1-3 years (with 3 years being more effective than 1 year for high-risk tumors) 2, 1
• Dosing: Full-dose BCG is recommended for maintenance therapy in high-risk patients 2

The FDA label for BCG intravesical therapy also supports this approach, stating: "intravesical BCG administration should continue at approximately monthly intervals for at least 6 to 12 months" after the initial 6-week induction course 3.

Follow-up and Surveillance Protocol

Regular surveillance is critical for this patient:

• Cystoscopy and urinary cytology: Every 3 months for the first 2 years, then every 6 months for years 3-4, and annually thereafter 2, 1
• Upper tract imaging: At least once within 2 years, then every 1-2 years for high-grade tumors 1
• Urine molecular tests: Optional (category 2B recommendation) 2

Response Evaluation

At the 3-month evaluation after completing the initial 6-week induction course:

• If normal cystoscopy and cytology persist: Continue with maintenance BCG therapy
• If recurrence is detected: Consider a second course of BCG induction (maximum of 2 consecutive courses) 2
• If disease persists after a second course of BCG: Consider radical cystectomy 2

Important Considerations and Pitfalls

1. Avoid premature discontinuation: Maintenance BCG significantly reduces recurrence rates compared to induction therapy alone 1

2. Monitor for BCG toxicity: If the patient cannot tolerate full-dose BCG maintenance, consider:

   • Dose reduction (though 1/3 dose may be suboptimal for high-risk patients) 4
   • Alternative intravesical agent like mitomycin C 2

3. BCG failure definitions: Be vigilant for signs of BCG failure, which include:

   • BCG-refractory: Persistent high-grade disease at 6 months despite adequate BCG
   • BCG-relapsing: Recurrence after achieving disease-free state at 6 months
   • BCG-unresponsive: Combination of refractory and relapsing within 6 months 2

4. Radical cystectomy timing: Early radical cystectomy should be considered if the patient develops BCG-unresponsive disease, as delaying cystectomy until progression to muscle-invasive disease may negatively impact survival 4

By following this evidence-based approach with appropriate maintenance therapy and vigilant surveillance, this patient has the best chance of long-term disease control and bladder preservation.