How to cite: Slovin SF. “The Evolving Role of Adjuvant Immunotherapy in RCC.” Grand Rounds in Urology. November 2025. Accessed Jan 2026. https://grandroundsinurology.com/the-evolving-role-of-adjuvant-immunotherapy-in-rcc/
Summary
Susan F. Slovin, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York, reviews the evolving role of systemic therapy in patients with high-risk localized or regionally advanced renal cell carcinoma (RCC) following nephrectomy. She begins by noting that approximately 15 to 20 percent of patients present with disease at high risk for relapse, and that recurrence rates have risen substantially over recent years, with 38 percent of such patients experiencing relapse within 18 months of follow-up.
Dr. Slovin discusses three pivotal TKI-based adjuvant trials (ASSURE, S-TRAC, and PROTECT), highlighting their divergent results and the controversy surrounding their interpretation. The ASSURE trial (sunitinib versus placebo) failed to demonstrate a disease-free or overall survival benefit. The S-TRAC trial showed a modest improvement in disease-free survival but no difference in overall survival, while PROTECT, evaluating pazopanib, demonstrated poor tolerability and no benefit. Collectively, these findings underscore the limitations of earlier vascular endothelial growth factor (VEGF)-targeted adjuvant strategies.
She transitions to the EVEREST trial, the first to evaluate everolimus, an mTOR inhibitor, as adjuvant therapy. The study, encompassing 1,500 patients, showed no improvement in recurrence-free or overall survival, with significant adverse events (46 percent grade 3 or higher) leading to poor tolerability.
Dr. Slovin highlights the landmark KEYNOTE-564 trial, which evaluated pembrolizumab versus placebo for one year in patients with intermediate- or high-risk clear cell RCC after surgery. The study demonstrated a statistically significant improvement in both disease-free and overall survival, leading to FDA approval of adjuvant pembrolizumab. However, she stresses that grade 3 or higher adverse events occurred in approximately 32 percent of treated patients, underscoring the need for individualized decision-making and long-term toxicity management.
She argues that the future of adjuvant therapy lies in improved risk stratification using tissue- and blood-based biomarkers, such as circulating tumor DNA and immune profiling, to identify patients most likely to benefit from immunotherapy while minimizing toxicity.
ABOUT THE AUTHOR
Susan F. Slovin, MD, PhD is a Genitourinary Medical Oncologist and Cellular Therapist, and the Associate Vice Chair of Academic Affairs for the Department of Medicine for the Memorial Sloan Kettering Cancer Institute in New York City, New York. Dr. Slovin specializes in prostate cancer, genitourinary cancers, cellular therapy, and clinical trials. Her clinical expertise is in clinical immunology, other genitourinary malignancies, internal medicine, and medical oncology.
Dr. Slovin earned her medical degree from Jefferson Medical College in Philadelphia, Pennsylvania. She completed a residency in Internal Medicine at Mount Sinai Hospital in New York, New York. Dr. Slovin then completed a fellowship in Clinical Immunology at Scripps Clinic & Research Foundation in La Jolla, California. She completed a fellowship in Medical Oncology/Hematology at Memorial Sloan Kettering Cancer Center in New York, New York. Dr. Slovin then completed a fellowship in Medicine at Weill Cornell Medical College in [New York, New York.
Dr. Slovin has won numerous awards in recognition for her contributions to the field, including America’s Top Doctor (2025, 2024, 2023), Exceptional Women in Medicine (2024, 2023), and the Top Doctor New York Metro Area (2023). She has published 222 articles and book chapters in her field and has been featured in theJournal of Clinical Oncology, European Urology Oncology,and theJournal of Immunotherapy and Precision Oncology.
