Revisiting Neoadjuvant Chemotherapy in Cisplatin-eligible Muscle-invasive Bladder Cancer

Management of muscle-invasive bladder cancer (MIBC) is evolving rapidly due to advances in systemic therapies and molecular understanding. Neoadjuvant cisplatin-based chemotherapy remains the cornerstone of cisplatin-eligible patients, supported by strong evidence of improved overall survival and pathological complete response. Phase 3 trials such as VESPER and NIAGARA have refined the standard of care by demonstrating the benefits of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin combination and chemoimmunotherapy, respectively. This review aims to summarize current and emerging neoadjuvant strategies and outline future directions toward a more individualized approach.

We reviewed the recent literature and pivotal clinical trial data evaluating neoadjuvant therapies for MIBC, with a focus on systemic chemotherapy, immunotherapy, combination regimens, novel agents, and biomarker-driven approaches. Emerging bladder-preserving strategies were also examined.

Neoadjuvant cisplatin-based chemotherapy remains the established benchmark; however, the NIAGARA trial has provided the first phase 3 evidence supporting neoadj chemo and perioperative IO as a new therapeutic option. The addition of durvalumab to cisplatin-based chemotherapy resulted in a significant improvement in survival and response endpoints. Antibody-drug conjugates and biomarkers such as circulating tumor DNA and DNA damage response mutations are shaping a more personalized treatment paradigm. However, optimal regimen selection, sequencing of therapies, and robust methods for response assessment remain unresolved.

Recent therapeutic advances, particularly the integration of immunotherapy, novel agents, and biomarker-driven strategies, are redefining the neoadjuvant landscape in MIBC. Neoadjuvant treatment for MIBC is moving toward a biomarker-informed risk-adapted approach, integrating novel agents and multidisciplinary decision-making. Refinement of patient selection and treatment sequencing will be critical to improving outcomes and advancing personalized, precision-based care.