From the Guidelines
Bacillus Calmette-Guérin (BCG) intravesical therapy is the recommended first-line treatment for carcinoma in situ (CIS) of the bladder, as it significantly reduces the recurrence rate compared to intravesical chemotherapy 1. The standard regimen consists of an induction course of six weekly instillations, followed by maintenance therapy for 1-3 years.
- For induction, a full dose of BCG (typically 50-81 mg depending on the strain) is instilled into the bladder and retained for 1-2 hours before voiding.
- After completing induction, maintenance therapy should follow with three weekly instillations at months 3,6,12,18,24, and 36. This extended maintenance schedule significantly improves disease-free survival compared to induction alone, as shown in a meta-analysis of 9 RCTs with a total of 1231 patients 1. BCG works by triggering a local immune response in the bladder, activating macrophages and T-lymphocytes that target and destroy cancer cells. Patients should be monitored with regular cystoscopies and urine cytology every 3-6 months during treatment to assess response. Common side effects include urinary frequency, dysuria, and mild flu-like symptoms, which typically resolve within 48 hours. If severe side effects occur, dose reduction to one-third or one-half may be considered. For patients who fail BCG therapy (persistent or recurrent CIS after adequate treatment), alternative options include radical cystectomy, alternative immunotherapies, such as pembrolizumab 1, or clinical trials.
From the Research
Treatment of Carcinoma In Situ (CIS) of the Bladder using BCG
- The standard treatment for CIS of the bladder is intravesical Bacillus Calmette-Guérin (BCG) therapy, which has been shown to reduce the risk of recurrence and progression 2, 3, 4.
- BCG immunotherapy is considered the first-line treatment for patients with CIS of the bladder, with complete and durable response rates reported in more than 70% of patients 2.
- The optimal therapeutic regimen for BCG therapy has not been established, although extended periods of treatment beyond the originally described 6-week course have not been shown to improve complete response rates 2.
- Prolonged administration of BCG is associated with adverse side effects, and clinicopathological factors remain the main indicators of response to BCG, recurrence, and progression 2, 3.
Alternative Treatment Options
- For patients who are refractory or resistant to BCG therapy, alternative treatment options include intravesical chemotherapy, combined immuno-chemotherapy, and radical cystectomy 2, 4, 5.
- Intravesical valrubicin and oral bropirimine have been shown to induce a complete response rate of 21% to 50% in patients with BCG-refractory CIS of the bladder 2.
- Radical cystectomy remains an effective therapy for aggressive CIS of the bladder, although it is typically considered a last resort 2, 4.
Recent Developments and Recommendations
- New optical imaging modalities have improved the detection of CIS of the bladder, and bladder preservation using BCG immunotherapy remains the cornerstone of treatment 3.
- A systematic review recommends the use of intravesical CG0070 adenovirus or hyperthermic intravesical chemotherapy mitomycin C in patients with CIS only disease, and alternative regimens for patients with CIS ± Ta/T1 disease or Ta/T1 disease only 5.
- More studies are needed to accurately assess the different medications and aid in designing guidelines for the management of BCG-unresponsive non-muscle invasive intravesical bladder cancer 5.