Bladder Preservation Therapy in Muscle-Invasive Bladder Cancer: Current Evidence and Future Directions.

Bladder preservation has emerged as an established treatment option for selected patients with muscle-invasive bladder cancer (MIBC), offering durable oncologic control with the potential to maintain native bladder function and quality of life. Over the past several decades, prospective trials and large institutional experiences have refined trimodality therapy (TMT)-maximal transurethral resection followed by definitive radiation therapy with concurrent radiosensitizing systemic therapy-and clarified principles of patient selection, treatment delivery, surveillance, and salvage. Randomized evidence supports combined-modality therapy as the backbone of bladder preservation, and contemporary comparative analyses suggest outcomes comparable to radical cystectomy in appropriately selected populations. This review synthesizes the clinical foundations of bladder preservation, including radiobiologic considerations, advances in radiation technique, and patterns of recurrence following TMT. We discuss outcomes in higher-risk populations, including locally advanced and node-positive disease, and examine the evolving integration of systemic therapies. The emergence of immune checkpoint inhibitors and antibody-drug conjugates in urothelial carcinoma has reshaped the systemic treatment landscape and raises important questions regarding patient selection, sequencing, and the potential expansion of organ-preserving strategies. Finally, we outline future directions-including response-adaptive approaches, advances in image-guided and adaptive radiotherapy, and ctDNA-enabled risk stratification-while emphasizing the need for prospective validation and multidisciplinary collaboration to refine and optimize bladder-preserving care.