What is the next step for a patient with a single focus of Carcinoma In Situ (CIS) of the bladder who has completed 6 intravesical Bacillus Calmette-Guérin (BCG) treatments?

Management After Completion of 6 Intravesical BCG Treatments for Single Focus CIS of the Bladder

The next step after completing 6 intravesical BCG treatments for a single focus of carcinoma in situ (CIS) of the bladder is to perform a full reevaluation at 3 months post-treatment initiation with cystoscopy, urinary cytology, and selected mapping biopsies to assess treatment response. 1

Evaluation of Treatment Response

• A complete evaluation should be performed 4-6 weeks after completing the 6-week BCG induction course (approximately 3 months from the start of therapy) 1
• The evaluation must include:
  • Cystoscopy with directed biopsies of any suspicious areas 1
  • Urinary cytology 1
  • Selected mapping biopsies if indicated by cystoscopy or cytology findings 1

Management Based on Response Assessment

If Complete Response (CR) is achieved:

• Maintenance BCG therapy is recommended as the preferred option, though it is technically optional 1

  • Maintenance BCG has been shown to improve outcomes compared to induction therapy alone 1
  • The optimal maintenance schedule is not firmly established, but typically continues for at least 1 year and up to 3 years 1

• Follow-up surveillance should include:

  • Urinary cytology and cystoscopy every 3 months for the first 2 years 1
  • Extended to every 6 months in years 3-4 if no recurrences 1
  • Annual surveillance thereafter 1
  • Imaging of the upper tract collecting system every 1-2 years 1

If Incomplete Response or Recurrence is found:

• For recurrent/persistent CIS detected at the 3-month evaluation:

  • A second 6-week course of BCG induction therapy may be given (no more than 2 consecutive induction courses) 1
  • If disease persists after a second course of BCG, radical cystectomy should be strongly considered 1

• Alternative options for BCG-unresponsive disease include:

  • Radical cystectomy (preferred option for BCG-unresponsive disease) 1
  • Intravesical therapy with a different agent (mitomycin, valrubicin) 1, 2
  • Pembrolizumab for patients with BCG-unresponsive CIS who are ineligible for or refuse cystectomy 1
  • Clinical trial participation 1

Important Considerations

• The definition of BCG-unresponsive disease includes:

  • BCG-refractory: persistent high-grade disease at 6 months despite adequate BCG treatment 1
  • BCG-relapsing: recurrence of high-grade disease after achieving disease-free state at 6 months 1

• Negative cystoscopy combined with negative cytology has a high negative predictive value (100% in some studies), which may allow for avoiding random bladder biopsies in these cases 3

• Long-term outcomes after BCG for CIS show:

  • Complete response rates of approximately 75-83% 4
  • 5-year disease-free rate of about 60% in complete responders 4
  • Risk of progression to muscle-invasive disease if BCG fails 5

• Special attention should be paid to the prostatic urethra during follow-up, as CIS can involve this area and represents a high risk for progression 5

Remember that CIS is a high-grade lesion with significant risk of progression to invasive bladder cancer if not adequately treated. The evaluation at 3 months is critical to determine the success of the initial BCG course and guide subsequent management decisions.