Bladder-preserving strategies for Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer; where are we and what will be expected?

Abstract

Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) is a new definition including patients who failed intravesical BCG therapy and should not receive more BCG because of the very low efficacy and disproportionately poor prognosis. Radical cystectomy as the standard of care for these patients is associated with significant morbidity and altered quality of life. Therefore, the FDA has accepted phase II single-arm studies as a threshold to approve new agents in this setting. Efforts to find an effective and safe bladder sparing strategy for BCG unresponsive patients have not been successful yet. Studies that assess nanoparticle-bound, combination or device-assisted intravesical chemotherapy to increase drug delivery and efficacy have been partly promising but suffer from limitations. Systemic immunotherapy such as checkpoint inhibitors therapy PD1/PDL1 and intravesical immunotherapy such as rAd-IFN/Syn3 have shown satisfactory efficacy so far. Although this is much effort and enthusiasm, no bladder-sparing strategy has met the criteria set for the successful alternative to radical cystectomy in BCG unresponsive NMIBC. For BCG unresponsive patients who refuse or are unfit for radical cyctectomy, there is new hope arising with novel strategies limiting the threshold for clinical use and a multitude of promising agents in clinical trials.