Bacillus Calmette-Guerin (BCG) and alternatives Drug treatment of high-risk non-muscle invasive bladder cancer

Background Intravesical instillation of bacillus Calmette-Guerin (BCG) is an accepted strategy to reduce the risk of recurrence and possibly progression of high-risk non-muscle invasive bladder cancer (NMIBC). However, side effects are not uncommon. In addition, the tumors may be BCG refractory or unresponsive. These tumors have a very high risk of recurrence and progression, so cystectomy must be weighed against conservative treatment options. Objectives We describe the current recommendations regarding treatment of NMIBC with BCG and alternatives for BCG failure. Methods Literature search on current treatment options and their alternatives with the help of mainly primary literature and guideline recommendations. Results and conclusion For high-risk NMIBC, instillation therapy with BCG remains standard-of-care, applied according to a standard regimen in terms of dose and dosing intervals (induction: weekly instillation for 6 weeks, maintenance: weekly instillation for 3 weeks, 3, 6 and 12 months after initiation of BCG therapy plus, for high-risk NMIBC, 18, 24, 30 and 36 months after initiation of BCG therapy). Potential future treatment options for BCG failure are systemic (i.v.) pembrolizumab (FDA approved) and, possibly, intravesical nadofaragene firadenovec. Ongoing randomized clinical trials are furthermore evaluating the role of PD-(L)1 immune checkpoint inhibitors in combination with BCG.