The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy.
This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN.
We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p < 0.001) were associated with worse CSM. Kaplan-Meier analyses revealed greater 5-yr rates for OS (51% vs 27%; p < 0.001) and CSS (83% vs 30%; p < 0.001) for IO +CN versus TKI + CN. This difference persisted in a subgroup analysis for patients with intermediate or poor risk, with 5-yr OS rates of 50% for IO + CN versus 30% for TKI + CN (p < 0.001). A subanalysis stratified by CN timing revealed better 5-yr rates for OS (50% vs 30%; p = 0.042) and CSS (90% vs 30%, p = 0.019) for delayed CN after IO therapy, but not after TKI therapy.
For patients who underwent CN, systemic therapy before CN was associated with better outcomes. In addition, IO therapy was associated with better survival outcomes in comparison to TKI therapy. Our findings question the applicability of clinical trial data from the TKI era to CN in the IO era for mRCC.
For patients with metastatic kidney cancer treated with surgery, better survival outcomes were observed for those who also received immunotherapy in comparison to therapy targeting specific proteins in the body (tyrosine kinase inhibitors, TKIs). Immunotherapy or TKI treatment resulted in better outcomes if it was received before rather than after surgery.
European urology open science. 2024 Mar 25*** epublish ***
Margaret F Meagher, Andrea Minervini, Maria C Mir, Clara Cerrato, Giacomo Rebez, Riccardo Autorino, Lance Hampton, Riccardo Campi, Maximilian Kriegmair, Estefania Linares, Vital Hevia, Maria Musquera, Mauricio D'Anna, Eduard Roussel, Maarten Albersen, Nicola Pavan, Francesco Claps, Alessandro Antonelli, Michele Marchioni, Nail Paksoy, Selcuk Erdem, Ithaar H Derweesh
Department of Urology, University of California-San Diego School of Medicine, La Jolla, USA., Department of Urology, University of Florence, Careggi Hospital, Florence, Italy., Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain., Department of Urology, University of Trieste, Trieste, Italy., Division of Urology, VCU Health, Richmond, VA, USA., Department of Urology, University Medical Centre Mannheim, Mannheim, Germany., Department of Urology, Hospital La Paz, Madrid, Spain., Department of Urology, Hospital Ramon y Cajal, Madrid, Spain., Department of Urology, Hospital Clinic Carrer de Villarroel, Barcelona, Spain., Department of Urology, KU Leuven, Leuven, Belgium., Department of Urology, University of Verona, Verona, Italy., Department of Urology, SS Annunziata Hospital, G. D'Annunzio University of Chieti, Chieti, Italy., Department of Urology, Faculty of Medicine, Istanbul University, Istanbul, Turkey.