New Treatment Options for Non-Muscle-Invasive Bladder Cancer.

Abstract

Non-muscle-invasive bladder cancer (NMIBC) comprises 75% of newly diagnosed bladder cancer and poses significant clinical challenges because of high recurrence and progression rates. Despite the effectiveness of Bacillus Calmette-Guérin (BCG) therapy after transurethral resection of bladder tumor (TURBT), BCG fails nearly 40% of patients, requiring alternative treatments. Traditionally, radical cystectomy has been the standard for BCG-unresponsive disease, although it significantly affects quality of life. Recent advances have focused on bladder-preserving therapies that leverage immune checkpoint inhibitors, viral gene therapies, novel drug delivery systems, and targeted molecular agents. Emerging approaches such as TAR-200 and UGN-102 offer novel intravesical delivery systems that enhance therapeutic efficacy while minimizing systemic adverse effects. Viral therapies, including nadofaragene firadenovec and CG0070, deliver immune-activating and oncolytic agents directly to urothelial tumor cells. Additionally, immune checkpoint inhibitors such as pembrolizumab and durvalumab have demonstrated potential for systemic treatments in BCG-unresponsive NMIBC and may show even more promise in combinations. Ongoing trials are expected to provide crucial data on these therapies' efficacy, particularly in high-risk and intermediate-risk populations. For low-grade NMIBC, efforts are underway to de-escalate care through active surveillance and novel adjuvant therapies, reducing the need for repeated TURBT procedures. Together, these advancements highlight a promising shift toward personalized, bladder-preserving strategies that prioritize patient quality of life while addressing unmet needs in NMIBC management.