How to cite: Dreicer R. “Management of Muscle-Invasive Bladder Cancer: Paradigm Shift?.” Grand Rounds in Urology. November 2025. Accessed Jan 2026. https://grandroundsinurology.com/management-of-muscle-invasive-bladder-cancer-paradigm-shift/
Summary
Robert Dreicer, MD, MS, MACP, FASCO, Professor of Medicine and Urology, University of Virginia School of Medicine, Charlottesville, Virginia, reviews the historical and current developments that continue to shape the management of muscle-invasive bladder cancer (MIBC). He begins with the origins of the cisplatin era, recalling the impact of early methotrexate, vinblastine, Adriamycin (doxorubicin), and cisplatin (MVAC) and cisplatin, methotrexate, and vinblastine (CMV) regimens, which first demonstrated the curative potential of chemotherapy for metastatic urothelial carcinoma. About 10 to 15 percent of patients with node-only or node-predominant disease could achieve long-term survival, leading to the adoption of perioperative cisplatin-based therapy as standard care.
For decades, this approach remained largely unchanged. Despite randomized data supporting its modest benefit, real-world adoption has lagged due to treatment complexity, patient comorbidities, and limited eligibility for patients with renal function issues.
Dr. Dreicer transitions to recent data from ESMO, where the combination of platinum chemotherapy with durvalumab showed improved event-free and overall survival compared to chemotherapy alone. The ongoing EV-304 trial, which tests enfortumab vedotin plus pembrolizumab (EVP) in the perioperative setting, has generated strong anticipation after its success in metastatic disease. EVP’s efficacy independent of renal function could fundamentally alter treatment selection for MIBC.
He also discusses the growing role of circulating tumor DNA (ctDNA) as a tool to guide decisions on adjuvant therapy. While ctDNA positivity appears predictive of recurrence, he notes that its clinical use remains investigational. Active cooperative-group studies are evaluating whether ctDNA-negative patients can safely avoid adjuvant therapy.
Dr. Dreicer argues that within a few years, platinum-based chemotherapy may no longer be the default perioperative regimen. Although EVP offers significant promise, its administration requires experience to manage neuropathy and dermatologic toxicity. The ongoing evolution toward ctDNA-informed, renal-function-agnostic therapy represents a true paradigm shift for MIBC.
ABOUT THE AUTHOR
Robert Dreicer, MD, MS, MACP, FASCO, is the Deputy Director and Associate Director of Clinical Research for the Cancer Center, Section Head of Solid Tumor Oncology within the School of Medicine’s Division of Hematology and Oncology, a Professor of Medicine and Urology, and the Co-Director of the Mellon Institute at the University of Virginia in Charlottesville, Virginia. Dr. Dreicer specializes in the management of genitourinary malignancies, as well as the design and conduct of clinical trials in urologic oncology. Dr. Dreicer’s research interests are in novel therapeutic approaches for urologic cancers including prostate, urothelial and kidney cancers.
