Cytoreductive nephrectomy in the age of immunotherapy-based combination treatment

Abstract

Renal cell carcinoma (RCC) displays a wide spectrum of oncological prognosis and clinical behavior, and is noted for its generally poor outcome in metastatic settings. However, the introduction of immunotherapy after the cytokine era has changed the landscape of treatment for metastatic RCC, outperforming previous targeted therapy and providing new hope for patients with advanced disease. Cytoreductive nephrectomy (CN) has been the center of controversy, with questionable survival benefit when compared to systemic therapy. Despite discouraging results from the two randomized clinical trials (CARMENA & SURTIME), interest into the role of CN is being rekindled, and contemporary real-world studies provide supporting evidence to suggest that CN may still have a role in well-selected patients treated or expecting treatment with immunotherapy, not only for symptomatic control but also for oncological benefit. In this review article, we attempt to review the modern insight into the role of CN for metastatic RCC in contemporary medicine, with a focus on treatment with immune checkpoint inhibitor combination-based immunotherapy.

Keywords: Immunotherapy; Nephrectomy; Renal cell carcinoma.

Fig. 1. (A) HR range of key clinical prognostic factors for CN and (B) median OS of CN vs. no CN from previous literature. CN, cytoreductive nephrectomy; HR, hazard ratio; IMDC, International Metastatic RCC Database Consortium; KPS, Karnofsky Performance Scale; OS, overall survival.

Fig. 2. Study designs of awaited clinical trials. CN, cytoreductive nephrectomy; CR, complete response; FDA, U.S. Food and Drug Administration; ICI, immune checkpoint inhibitor; IO, immuno-oncology; mRCC, metastatic renal cell carcinoma; OS, overall survival.