Antibody–drug conjugates for non-muscle invasive bladder cancer: current status and future development

PURPOSE OF REVIEW: Antibody-drug conjugates (ADCs) have recently emerged as a promising targeted therapeutic strategy in urothelial carcinoma, and their application in nonmuscle invasive bladder cancer (NMIBC) is an evolving frontier. This review is timely as it synthesizes recent advances in ADC development for NMIBC, addressing critical unmet needs among both Bacillus Calmette-Guérin (BCG) naïve high-risk and BCG-unresponsive patients. RECENT FINDINGS: The literature reveals that ADCs that target HER2, Trop-2, Nectin-4 are under active investigation. Several retrospective and prospective studies have reported encouraging complete response rates, durable event-free survival, and manageable safety profiles with these agents. Current clinical trials are evaluating ADCs as monotherapy or in combination with immune checkpoint inhibitors (e.g., durvalumab, tislelizumab) and intravesical therapies, aiming to refine dosing regimens and maximize therapeutic efficacy. SUMMARY: The findings underscore the potential of ADCs to revolutionize NMIBC management by providing novel bladder-sparing strategies in patients traditionally limited by BCG failure. Future research should concentrate on optimizing patient selection, treatment sequencing, and combination strategies to improve long-term outcomes, enhancing survival and quality of life.