What We Have Learnt from CARMENA and SURTIME and What Should Be Done Differently in Future Trials on Cytoreductive Nephrectomy

Abstract

Upfront cytoreductive nephrectomy (CN) was the standard treatment for selected patients with metastatic Renal Cell Carcinoma (RCC) in the cytokine era for many years. In the recent ‘targeted therapy era’ it has been re-challenged by both the CARMENA and SURTIME trials. As first-line therapy for treatment-naive metastatic clear-cell RCC has now changed to immune checkpoint inhibitor combination therapy (ICI), and previous studies concerning CN were built in the targeted therapy era, the role and sequence of CN needs to be revisited. Here we address what we learned from both trials and how future trials should be designed to investigate CN.

Cytoreductive nephrectomy in the age of immunotherapy-based combination treatment

“…In a post-hoc analysis of the sunitinib-alone arm, 40 patients who underwent deferred CN showed improved OS compared to those not receiving surgery, with a median 48.5 vs. 15.7 months, respectively [ 25 ]. Subgroup analyses of the intermediate risk groups in the CARMENA trial with 2 IMDC risk factors as well as 89% of the SURTIME participants indicated a favorable prognosis in the deferred CN or sunitinib alone arms compared to upfront nephrectomy (31.2 vs. 17.6 mo in the CARMENA trial and 34.2 vs. 15.0 mo in the SURTIME trial, respectively) [ 26 ]. Singla et al [ 23 ] found similar results, with patients receiving deferred CN having lower pathologic stage, grade, tumor size, and lymphovascular invasion in comparison to those undergoing upfront CN in a subgroup analysis in IO+CN patients from a national registry.…”