Perioperative Systemic Therapy Adjuvant IO: Integrating Systemic Treatments with Surgical Management

How to cite: Palaskas NJ. “Perioperative Systemic Therapy – Adjuvant IO: Integrating Systemic Treatments with Surgical Management.” November 13, 2025. Accessed Apr 2026. https://grandroundsinurology.com/perioperative-systemic-therapy-adjuvant-io-integrating-systemic-treatments-with-surgical-management/

Summary

Nicolaos J. Palaskas, MD, PhD, Assistant Professor and member of the Jonsson Comprehensive Cancer Center’s Cancer and Stem Cell Biology Program, University of California, Los Angeles, Los Angeles, California, examines the role of adjuvant immunotherapy following radical cystectomy, arguing that while perioperative immunotherapy improves outcomes, current evidence does not definitively establish superiority over a carefully selected adjuvant-only approach. Dr. Palaskas reviews trial data and emphasizes that adjuvant immunotherapy may offer theoretical and practical advantages when guided by postoperative pathologic and biomarker risk stratification.

The presentation opens with a review of National Comprehensive Cancer Network (NCCN) recommendations for stage II and III bladder cancer in patients not pursuing bladder preservation. Standard pathways include neoadjuvant cisplatin-based chemotherapy followed by adjuvant therapy in the presence of residual high-risk disease, or cystectomy alone with adjuvant treatment reserved for patients with adverse pathologic features.

Dr. Palaskas reviews key adjuvant immunotherapy trials. CheckMate 274 demonstrated a meaningful improvement in disease-free survival with adjuvant nivolumab, along with a modest overall survival benefit. The AMBASSADOR trial also showed an improvement in disease-free survival with pembrolizumab, though an overall survival benefit was not observed, likely due to crossover and subsequent immunotherapy exposure. IMvigor010 failed to meet its primary endpoint, underscoring the limitations of unselected adjuvant therapy.

He contrasts these results with perioperative data from the NIAGARA trial. While perioperative durvalumab improved event-free and overall survival, Dr. Palaskas notes that the magnitude of benefit closely mirrors that seen in adjuvant-only trials, raising the question of whether perioperative exposure is required for all patients.

Dr. Palaskas focuses on postoperative circulating tumor DNA (ctDNA). Data from NIAGARA demonstrate that ctDNA positivity after cystectomy portends poor prognosis, yet immunotherapy provides benefit regardless of ctDNA status at a single time point. In contrast, IMvigor011 suggests that serial ctDNA monitoring may better identify patients who benefit from adjuvant immunotherapy.

Dr. Palaskas highlights the MODERN trial, which aims to clarify optimal timing and escalation of adjuvant immunotherapy based on minimal residual disease status. His presentation provides a balanced perspective on integrating systemic therapy with surgical management.

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.