Outcomes of Consolidative Nephrectomy Following Primary Immunotherapy in Advanced Renal Cell Carcinoma: A Multicenter Analysis.

Primary systemic therapy in the management of advanced Renal Cell Carcinoma (RCC) has gained increasing traction. We examined immunotherapy (IO) followed by cytoreductive nephrectomy (CRN) in 56 patients with mostly favorable/intermediate IMDC risk. IO significantly reduced tumor /thrombus size, complexity, and clini-cal/pathologic stage. A quality CRN (negative margins and without complications) following IO demonstrated improved 2-year progression-free survival.Background: To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC). Methods: We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) follow-ing surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multi-variable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups. Results: A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size ( P < .001), thrombus size ( P = .02), and RENAL score ( P < .001); 38 (67.9%) patients were clinically downstaged on imaging ( P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery ( P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019). Conclusions: Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer.Clinical Genitourinary Cancer, Vol. 21, No. 6, 694-702 (c) 2023 Elsevier Inc. All rights reserved.