How to cite: Stewart TF. Perioperative systemic therapy: perioperative immunotherapy. Grand Rounds in Urology. November 2025. Accessed February 2026. https://grandroundsinurology.com/perioperative-systemic-therapy-perioperative-immunotherapy/
Summary
Tyler F. Stewart, MD, Associate Clinical Professor of Medicine, University of California, San Diego, San Diego, California, argues that perioperative immunotherapy should be considered the standard of care for patients with muscle-invasive bladder cancer who are candidates for cystectomy. Dr. Stewart presents a data-driven case that systemic therapy before and after surgery improves event-free survival and overall survival, and that current evidence does not reliably identify a subgroup that can safely forgo immunotherapy.
He reviews outcomes for cystectomy alone, highlighting poor event-free survival in real-world muscle-invasive bladder cancer populations. Historic data establishing neoadjuvant cisplatin-based chemotherapy as a survival-improving intervention are reviewed, including the Grossman trial and subsequent studies comparing gemcitabine cisplatin with dose-dense combination methotrexate, vinblastine, adriamycin (doxorubicin), and cisplatin (MVAC).
Dr. Stewart shifts to the immunotherapy era, summarizing mixed results from adjuvant-only trials. IMvigor010 failed to show benefit with adjuvant atezolizumab, AMBASSADOR demonstrated disease-free survival improvement without a clear overall survival advantage, and CheckMate 274 showed a significant disease-free survival benefit with nivolumab and a strong trend toward improved overall survival. These studies established adjuvant immunotherapy as an active but incomplete solution.
The core of his argument centers on the NIAGARA trial, which evaluated neoadjuvant gemcitabine cisplatin with or without preioperative durvalumab. He notes that NIAGARA demonstrated statistically significant improvements in both event-free survival and overall survival with perioperative immunotherapy. Subgroup analyses showed consistent benefit across disease stages and regardless of baseline circulating tumor DNA status, indicating that neither stage nor ctDNA reliably identifies patients who do not benefit.
Dr. Stewart then reviews KEYNOTE-905 and EV-303, evaluating perioperative enfortumab vedotin plus pembrolizumab in cisplatin-ineligible patients. This study showed dramatic improvements in event-free survival and overall survival, with pathologic complete response rates approaching 57 percent, reinforcing the role of antibody-drug conjugate plus immunotherapy combinations in the perioperative setting.
Dr. Stewart argues that perioperative immunotherapy should be strongly considered for all eligible patients with muscle-invasive bladder cancer, while ongoing trials such as EV-304 and VOLGA will further refine standards of care.
About the 32nd Annual Perspectives in Urology: Point Counterpoint conference: Presented by Program Chair and Grand Rounds in Urology Editor-in-Chief E. David Crawford, MD, this conference brought together leading experts in urology, medical oncology, and radiation oncology to discuss and debate the latest topics in genitourinary cancers, primarily prostate cancer and bladder cancer. This interactive conference offered topical lectures, pro/con debates, interesting-case presentations, interactive panel discussions, and interactive audience and faculty networking.
ABOUT THE AUTHOR
Tyler F. Stewart, MD, is a medical oncologist and Associate Clinical Professor of Medicine at the University of California, San Diego. He is part of UC San Diego Health’s Precision Immunotherapy Clinic. Dr. Stewart designs and directs clinical trials with novel therapeutics; his research focuses on personalizing cancer therapy using biomarkers.
