Perioperative treatment for muscle invasive bladder cancer in the era of immunotherapy.

Muscle-invasive bladder cancer (MIBC) remains associated with high recurrence and mortality despite radical cystectomy and cisplatin-based neoadjuvant chemotherapy (NAC). For decades, perioperative therapy was defined by platinum-based regimens, which improve survival but are limited to fewer than half of patients due to comorbidities. Recent advances in the past year have redefined this landscape. Multiple pivotal phase III trials have demonstrated the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings. The phase III trials, KEYNOTE-905/EV-303 and KEYNOTE-B15/EV-304 have established perioperative enfortumab vedotin plus pembrolizumab as a new standard of care for neoadjuvant therapy. Parallel translational research has identified biomarkers that may refine patient selection and optimize therapy. PD-L1 expression, DNA damage repair gene alterations, molecular subtyping, and circulating tumor DNA (ctDNA) have all emerged as predictive and prognostic tools. Liquid biopsy approaches may guide adjuvant therapy decisions and facilitate real-time monitoring of minimal residual disease. This review synthesizes the evolving role of perioperative therapies in MIBC, from the historical reliance on cisplatin-based chemotherapy to the transformative integration of immunotherapy, ADCs, and biomarker-guided approaches. Together, these advances represent a significant progress in perioperative bladder cancer care, heralding a shift toward individualized, biomarker-driven strategies that promise improved survival and broader treatment applicability.