Neoadjuvant Therapy in Muscle-Invasive Bladder Cancer: Current Evidence, Evolving Strategies, and Future Directions.

Neoadjuvant therapy is now a cornerstone of muscle-invasive bladder cancer management, evolving from traditional cisplatin-based chemotherapy to novel immunotherapy and antibody-drug conjugate combinations. While dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin remains the cytotoxic standard, the phase III NIAGARA and KEYNOTE 905 trials have established new benchmarks for cisplatin-eligible and ineligible populations, respectively. Furthermore, the integration of molecular subtyping, DNA damage repair biomarkers, and liquid biopsies (circulating tumor DNA) is facilitating a shift toward precision medicine. These advancements aim to optimize pathologic response, improve overall survival, and identify candidates for bladder-sparing approaches.