Bladder Preservation Strategies in Muscle-Invasive Bladder Cancer

Muscle-invasive bladder cancer (MIBC) has historically been managed with neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy (RC), a strategy associated with substantial morbidity and long-term quality-of-life implications. As systemic therapies achieve increasingly deep responses, interest has intensified in bladder-preserving approaches that maintain oncologic efficacy while minimizing treatment-related burden. This review examines the evolving landscape of bladder preservation in MIBC, spanning radiation-based trimodality therapy (TMT), partial cystectomy, and emerging response-adapted strategies after neoadjuvant therapy. We summarize long-term oncologic outcomes of TMT, which, in carefully selected patients, provides disease-specific and overall survival (OS) results comparable with RC outcomes with durable bladder preservation in many long-term survivors. We review patient selection criteria, the role of maximal transurethral resection, and optimal radiosensitizing regimens, as well as ongoing efforts to integrate immunotherapy into definitive chemoradiation. Beyond radiation-based strategies, we highlight growing interest in active surveillance after clinical complete response (CR) to neoadjuvant chemotherapy or chemo-immunotherapy, an approach enabled by unprecedented pathologic CR rates achieved with modern regimens, including enfortumab vedotin plus pembrolizumab. A central challenge to response-adapted bladder preservation remains the accurate identification of patients with true eradication of local and systemic disease. We discuss limitations of conventional clinical restaging and review advances in multiparametric magnetic resonance imaging, fluorodeoxyglucose positron emission tomography/computed tomography, circulating tumor DNA, and urinary tumor DNA as complementary tools for response assessment, risk stratification, and early detection of recurrence. Finally, we outline future directions focused on integrating molecular biomarkers, advanced imaging, and multidisciplinary decision making to safely expand bladder preservation while preserving metastasis-free survival and OS.