Clinical outcomes of deferred cytoreductive nephrectomy after initial systemic therapy in metastatic renal cell carcinoma: A multicenter retrospective study

Rioja P.; Passarella C.; Angel M.; Valderrama W.; Ainaud F.B.; Anguera G.; Gómez V.; Ruiz-Granados Á.; Plata D.; Zapata M.I.; Orta-Ruiz A.; Quiroga M.N.G.; Bourlon M.T.; Grande E.; Ray Manneh Kopp; Molina-Cerrillo J.; Maroto P.; Sade J.P.; Castellano D. · Urologic Oncology: Seminars and Original Investigations (2026) · DOI: 10.1016/j.urolonc.2026.04.008

Resumen

Introduction Deferred cytoreductive nephrectomy (dCN) is a selective strategy for managing metastatic renal cell carcinoma (mRCC), in the era of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI), particularly for patients who achieve favorable responses to initial systemic therapy. This study aims to describe the clinical outcomes of dCN following first-line systemic treatment within a sequential management approach. Methods This multi-institutional retrospective study included 50 patients with clear cell mRCC who underwent dCN after first-line therapy. Patients were categorized according to treatment regimen (TKI monotherapy or ICI-based combinations). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Prognostic factors were evaluated with Cox proportional hazards regression. A P -value ' 0.05 was considered statistically significant. Results Median follow-up was 19 months (range 1–174 months). First-line therapy included ICI + ICI in 24%, ICI + TKI in 46%, and TKI alone in 30% of patients. The overall response rate was 64%, and the disease control rate was 84%. Median time from systemic therapy initiation to cytoreductive nephrectomy was 5.6 months. Median PFS was 36 months, 12-, 36-, and 60-month PFS rates of 77%, 49%, and 40%, respectively. Longer PFS occurred in patients with a Karnofsky performance status (KPS) '80% (51 vs. 14 months; P = 0.037) and complete response (P = 0.0021). Median OS reached 91 months. Limitations included a retrospective design and a modest sample size. Conclusions dCN may offer durable benefit in well-selected patients achieving disease control and good performance status after systemic therapy. The optimal timing remains uncertain and warrants validation in larger prospective trials.

Instituciones: Universidad San Ignacio de Loyola