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Objective: To use econometric methods to assess comparative overall survival of patients with metastatic renal cell carcinoma (mRCC) managed with initial cytoreductive nephrectomy (CN) vs initial systemic therapy. Randomized data demonstrate improved survival for CN preceding cytokine-based therapy in mRCC. This benefit may be attenuated in the contemporary mRCC era given more effective systemic therapies., Methods: Patients over age 65 with mRCC from the Surveillance, Epidemiology, and End Results registries linked with Medicare claims from 2006 to 2011 were categorized by initial treatment. We applied sequential survival analysis methods to assess the association between initial CN and overall survival (OS) including Cox proportional hazards models, propensity scoring, and instrumental variable analysis to account for measured and unmeasured selection bias., Results: Of 537 patients analyzed, 190 had initial CN followed by targeted therapy and 347 had initial targeted therapy. Median OS in the initial CN group was 17.4 months (interquartile range 9.8-32.0), compared with 9.2 months (interquartile range 4.3-18.0) for initial targeted therapy. Cox proportional hazards analysis revealed initial CN was associated with improved OS (hazard ratio 0.50, 95% confidence interval [CI] 0.38-0.65). Propensity matching demonstrated a survival advantage for initial CN of 5.8 months (95% CI 1.9-9.7). Accounting for unmeasured confounding with instrumental variable analysis demonstrated a trend toward improved survival with initial CN (hazard ratio 0.29 [95% CI 0.08-1.00])., Conclusion: Initial CN is associated with improved survival compared with initial systemic therapy in a contemporary population-based mRCC cohort., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The randomized, phase 3 CheckMate 025 study of nivolumab (n=410) versus everolimus (n=411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR)., Objective: To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus., Design, Setting, and Participants: Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model., Intervention: Nivolumab 3mg/kg every 2 wk or everolimus 10mg once daily., Results and Limitations: The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age <65 and ≥65 yr; one and two or more sites of metastases; bone, liver, and lung metastases; number of prior therapies; duration of prior therapy; and prior sunitinib, pazopanib, or interleukin-2 therapy. The benefit with nivolumab versus everolimus was noteworthy for patients with poor MSKCC risk (hazard ratio 0.48, 95% confidence interval 0.32-0.70). The mortality rate at 12 mo for all subgroups was lower with nivolumab compared with everolimus. ORR also favored nivolumab. The incidence of grade 3 or 4 treatment-related adverse events across subgroups was lower with nivolumab. Limitations include the post hoc analysis and differing sample sizes between groups., Conclusion: The trend for OS and ORR benefit with nivolumab for multiple subgroups, without notable safety concerns, may help to guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC., Patient Summary: We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate population-based survival trends, compared to optimistic trial benchmarks, in metastatic renal cell carcinoma (mRCC). Advances in medical therapy for mRCC may be associated with survival improvements. Yet, targeted therapy trial results focus on patients with favorable-risk mRCC and may not be well disseminated at the population level., Methods: Surveillance, Epidemiology, and End Results identified adult mRCC patients diagnosed between 1990 and 2009. Survival was analyzed by treatment era (cytokine, 1990-2005; targeted therapy, 2006-2009) and stratified by histology. Multivariate Cox regression identified factors independently associated with overall survival., Results: We identified 14,521 eligible patients. For clear cell mRCC (N = 4149), median survival improved from 11 to 14 months before and after targeted therapy (P <.001). For RCC with sarcomatoid features (N = 608) and RCC not otherwise specified (N = 8860), survival did not change (median survival 4 months for both). For non-clear cell subtypes (N = 904), median survival improved from 7 to 9 months (P = .008). On multivariate analysis, factors associated with increased overall survival were as follows: treatment in the targeted era (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.84-0.91), clear cell histology (HR, 0.76; 95% CI, 0.73-0.80), and receipt of surgery (HR, 0.43; 95% CI, 0.41-0.46)., Conclusion: Population-based mRCC median survival improved but to a lesser degree than that reported in clinical trials. This represents opportunity for quality improvement in histologically guided care, use of cytoreductive nephrectomy, and development of strategies for trial-ineligible, poor-risk patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)