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

Management of Bladder CIS After BCG Induction with Complete Response and Mild Atypia

For a 60-year-old man with CIS of the bladder who received an induction course of BCG and now shows no residual tumor but mild atypia on follow-up biopsy, maintenance BCG therapy is the recommended next step.

Understanding the Clinical Scenario

This patient has:

• History of carcinoma in situ (CIS) of the bladder
• Completed induction BCG therapy (6 weekly instillations)
• Follow-up biopsy showing no residual tumor but mild atypia
• No evidence of progression to invasive disease

Recommended Management Algorithm

1. Initiate Maintenance BCG Therapy

• The NCCN guidelines recommend maintenance BCG therapy for patients with high-risk non-muscle invasive bladder cancer (including CIS) who have responded to induction therapy 1, 2
• Maintenance BCG significantly reduces the risk of recurrence compared to induction therapy alone 1
• The optimal maintenance schedule consists of:
  • 3 weekly instillations at 3,6, and 12 months after induction for at least 1 year 1
  • For high-risk patients like those with CIS, extending maintenance to 3 years is recommended 1

2. Follow-up Schedule

• Cystoscopy and urinary cytology every 3 months for the first 2 years 1, 2
• Then extend to every 6 months for years 3-4, and annually thereafter 2
• Upper tract imaging (CT urography, IVP, or MRI urogram) at least once within the first 2 years, then every 1-2 years for high-grade tumors like CIS 2

3. Monitoring for Recurrence or Progression

• If recurrence is detected during follow-up:
  • For recurrent CIS: A second course of BCG induction may be given (maximum of 2 consecutive courses) 1
  • If disease persists after a second course of BCG, consider cystectomy or alternative intravesical agents 1
• For progression to muscle-invasive disease, radical cystectomy is recommended 2

Evidence Supporting This Approach

The NCCN guidelines clearly state that for patients with CIS who show no residual disease at follow-up after induction BCG, maintenance BCG therapy is recommended 1. This is based on evidence that maintenance therapy produces better outcomes than induction therapy alone 1.

The ESMO guidelines similarly recommend full-dose intravesical BCG for 1-3 years (at least 1 year) for high-risk non-muscle invasive bladder cancer, including CIS 1.

Important Considerations and Caveats

Mild Atypia

• The presence of mild atypia without residual tumor still warrants maintenance therapy and close follow-up
• Atypia may represent early recurrence or treatment effect
• Close surveillance is essential to detect any progression early

BCG Administration

• BCG should be retained in the bladder for 2 hours for optimal effect 3
• Patient should be repositioned every 15 minutes during retention to maximize bladder surface exposure 3
• Monitor for side effects including frequency (65%), dysuria (63%), and hematuria (43%) 4

Risk of Progression

• CIS is a high-grade lesion with significant risk of progression to invasive disease if not properly treated 2
• Long-term studies show that with proper BCG therapy, disease-specific mortality can be as low as 1.4% 5
• However, progression risk remains, particularly for CIS associated with T1 papillary tumors 5

Alternative Options

If the patient is unable to tolerate BCG maintenance therapy:

• Intravesical mitomycin C may be considered as an alternative 1
• For BCG-refractory disease, valrubicin is FDA-approved, though its efficacy is debated 1, 6

By following this evidence-based approach with maintenance BCG therapy, the patient has the best chance of preventing recurrence and progression of bladder CIS while preserving quality of life.