Clinical and pathological outcomes of deferred nephrectomy in patients with metastatic and locally advanced RCC after immune checkpoint inhibitors.

Abstract

Background and objective: Cytoreductive nephrectomy following immune checkpoint blockade (ICB) in metastatic renal cell carcinoma remains controversial, with limited data on its clinical and pathological outcomes. This study evaluated the outcomes of patients undergoing deferred cytoreductive nephrectomy (dCN) after ICB-based treatment, focusing on the radiologic and pathological responses, and postoperative clinical outcomes.

Methods: We retrospectively reviewed 24 patients with metastatic or locally advanced RCC who underwent dCN after ICB at a single institution between April 2018 and May 2024. We assessed the radiological response to ICB, pathological findings (presence and extent of necrosis) in resected primary tumors, and postoperative clinical outcomes, including the rate of patients without measurable disease and those who discontinued systemic therapy.

Results: Median ICB exposure prior to surgery was 11.3 months. Radiologically, 67% of patients had partial response, 29% had stable disease, and 4% had a complete response. Pathology showed 96% of specimens with necrosis, 21% of specimens showing no residual disease (pT0), and 21% exhibiting ≥95% necrosis. Postoperatively, 50% of patients had nonmeasurable disease of first follow-up scans, and 54% discontinued systemic therapy, with 9 patients remaining on surveillance at last follow-up. Limitations include the small sample size and retrospective design.

Conclusion: Deferred CN following ICB therapy is feasible. Extensive necrosis in the resected surgical specimen after ICB-based therapy requires further investigation as a prognostic marker for durable responses off systemic therapy.