Pharmacologic Therapies for Non-Muscle Invasive Bladder Cancer: Current and Future Treatments

Bladder cancer is the sixth most common malignancy in the United States and 70% of cases are non-muscle invasive at the time of diagnosis. Effective treatment is crucial to prevent progression, which occurs in about 30% of patients. The American Urological Association (AUA) guidelines recommend treatment of non-muscle invasive bladder cancer (NMIBC) with intravesical Bacille Calmette-Guerin (BCG) and chemotherapy. However, ongoing shortages and high rates of BCG unresponsiveness creates a major need for novel therapies. In this narrative review, we discuss the evolving landscape of therapeutic options for NMIBC. Pembrolizumab, an anti-programmed cell death (PD)-1 antibody, was the first systemic therapy to be FDA-approved for BCG-unresponsive, high-risk disease. Promising new agents under investigation include various other checkpoint inhibitors and adenovirus-based therapies including CG0070 and nadofaragene firadenovec (rAd-IFNa/Syn3). Finally, new mechanisms of drug delivery are under investigation, including delivery with the GemRIS (TAR-200) device and delivery of intravesical chemotherapy at higher temperatures. With the promise of novel therapies on the horizon, we can expect the role of urologists in the management of NMIBC to evolve and expand.