Neoadjuvant and Adjuvant Treatment for the Management of Upper Tract Disease

How to cite: Gupta S. Neoadjuvant and Adjuvant Treatment for the Management of Upper Tract Disease. Grand Rounds in Urology. December 2025. Accessed Apr 2026. https://grandroundsinurology.com/neoadjuvant-and-adjuvant-treatment-for-the-management-of-upper-tract-disease/

Summary

Shilpa Gupta, MD, Director of Genitourinary Medical Oncology and Co-Leader of the Genitourinary Oncology Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, reviews the evolving role of neoadjuvant and adjuvant systemic therapy in upper tract urothelial carcinoma, highlighting evidence supporting platinum-based chemotherapy and the limited role of immunotherapy in this setting.

Meta-analyses in muscle-invasive bladder cancer demonstrate overall survival benefit with neoadjuvant cisplatin-based chemotherapy, and similar principles inform upper tract management. However, approximately half of patients are ineligible for cisplatin, and many decline therapy.

In the adjuvant setting for urothelial carcinoma, platinum-based chemotherapy improves disease-free survival, with meta-analyses showing modest absolute overall survival benefit at five years. Adjuvant immunotherapy trials in high-risk muscle-invasive urothelial carcinoma demonstrate disease-free survival benefit in some studies but have not consistently shown overall survival improvement. Subgroup analyses of upper tract populations within these trials do not demonstrate a clear benefit with adjuvant immunotherapy.

For upper tract disease specifically, the POUT trial established adjuvant platinum-based chemotherapy as the standard of care for high-risk patients after nephroureterectomy, demonstrating improved disease-free survival compared with surveillance.

Neoadjuvant therapy in upper tract disease remains less widely adopted but is biologically appealing. After nephroureterectomy, renal function often declines, precluding cisplatin eligibility. A phase II study evaluating four cycles of split-dose gemcitabine and cisplatin before surgery demonstrated substantial pathologic downstaging and favorable progression-free survival, though staging challenges persist due to limited biopsy sampling.

Dr. Gupta emphasizes that neoadjuvant cisplatin-based chemotherapy is preferred when renal function allows. If neoadjuvant therapy is not given, adjuvant platinum-based chemotherapy is standard. Adjuvant immunotherapy has not demonstrated consistent benefit in upper tract disease. Future directions include antibody-drug conjugate combinations, molecular selection including FGFR-targeted strategies, and response-adapted organ-preserving approaches.