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 on follow-up biopsy, but shows mild atypia on cytology?

Management of CIS Bladder Cancer After BCG Induction with No Residual Tumor but Mild Atypia on Cytology

For a 60-year-old man with CIS of the bladder who received BCG induction therapy and has no residual tumor on follow-up biopsy but shows mild atypia on cytology, the next step should be to initiate maintenance BCG therapy. 1

Rationale for Maintenance BCG

The International Bladder Cancer Group and NCCN 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 1. This recommendation is based on:

• CIS is considered high-risk NMIBC with significant potential for recurrence and progression
• Maintenance BCG has been shown to reduce recurrence rates in patients with high-risk disease
• The presence of mild atypia on cytology warrants continued vigilance and treatment

Maintenance BCG Schedule

The recommended maintenance schedule should follow:

• Three weekly instillations at months 3,6, and 12 after induction
• Continue with three weekly instillations at months 18,24,30, and 36 1
• Full-dose intravesical BCG for 1-3 years is recommended for high-risk NMIBC patients, including those with CIS 1

Surveillance Protocol

Regular surveillance is critical and should include:

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

Management of Persistent Atypia

The mild atypia on cytology requires close monitoring:

• If cytology becomes positive during follow-up but cystoscopy remains negative, selected mapping biopsies including TUR of the prostate are indicated 2
• Upper tract evaluation should be performed to rule out upper tract urothelial carcinoma
• Enhanced cystoscopy (blue light or narrow band imaging) should be considered if available 2

Warning Signs and Alternative Management

Be vigilant for signs of disease recurrence or progression:

• If cytology worsens or becomes positive with negative cystoscopy, mapping biopsies are indicated
• If recurrence is detected during maintenance therapy, consider a second course of BCG induction (maximum of 2 consecutive courses) 2
• For BCG-unresponsive disease, options include cystectomy, changing the intravesical agent, or pembrolizumab (for patients ineligible for cystectomy) 2, 1

Potential Pitfalls and Caveats

1. Don't underestimate mild atypia: While mild atypia doesn't necessarily indicate recurrence, it warrants close surveillance as it may represent early recurrence.

2. Avoid inadequate follow-up: Skipping or delaying scheduled cystoscopy and cytology can lead to missed recurrences.

3. Don't ignore upper tract evaluation: Upper tract recurrence can occur and should be ruled out, especially with positive cytology and negative cystoscopy.

4. Recognize BCG failure patterns: Be aware of BCG-refractory, BCG-relapsing, and BCG-unresponsive disease patterns that would require alternative management 1.

5. Consider patient tolerance: Monitor for BCG side effects; if the patient cannot tolerate full-dose BCG maintenance, consider dose reduction or alternative intravesical agents like mitomycin C 1.