Bladder-Preserving Platforms for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

Bacillus Calmette Guerin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC) remains a difficult clinical setting in which radical cystectomy offers the most reliable oncologic control but is not feasible or acceptable for many patients. This review examines contemporary bladder-preserving strategies, with emphasis on biologic intravesical platforms, device-assisted drug-delivery systems, systemic immunotherapy, and pragmatic intravesical chemotherapy alternatives. These approaches should not be viewed as interchangeable. Biologic platforms seek to restore or intensify local antitumor immunity, whereas device-assisted strategies aim to overcome the pharmacokinetic limitations of conventional intravesical therapy by improving residence time, exposure, or tissue penetration. Across platforms, clinically meaningful activity has been reported, but current evidence remains constrained by single-arm study designs, heterogeneous eligibility criteria, non-equivalent endpoints, and variable follow-up maturity. As a result, available data support expansion of bladder-preserving options but do not establish a definitive treatment hierarchy. In clinical practice, differences in durability, toxicity, treatment burden, BCG dependence, device requirements, access, and biomarker eligibility may be as important as initial response rates. The central challenge is therefore shifting from whether bladder preservation is possible to how available options should be selected, sequenced, and integrated for individual patients. More harmonized comparative evidence, mature post-failure data, and clinically deployable biomarker frameworks will be needed to guide future treatment allocation.