Survival after Cytoreductive Nephrectomy in Metastatic Non-clear Cell Renal Cell Carcinoma Patients: A Population-based Study

Background: The benefit of cytoreductive nephrectomy (CNT) for cancer-specific mortality (CSM)-free survival is unclear in contemporary metastatic non-clear cell renal cell carcinoma (non-ccmRCC) patients. Objective: To assess the role of CNT in non-ccmRCC patients. Design, setting, and participants: Within Surveillance, Epidemiology, and End Results registry (2001–2014), we identified patients with non-ccmRCC. Intervention: CNT versus no CNT in non-ccmRCC patients. Outcome measurements and statistical analysis: Multivariable logistic regression, cumulative incidence, competing-risks regression models, incremental survival benefit (ISB), conditional survival, and landmark analyses were performed. Sensitivity analyses focused on histological subtypes and most contemporary patients (2010–2014). Results and limitations: Of 851 patients with non-ccmRCC, 67.6% underwent CNT. In multivariable logistic regression, year of diagnosis in contemporary (p < 0.001) and intermediate (p = 0.008) tertiles, as well as age ≥75 yr (p < 0.001) yielded lower CNT rates. Cumulative incidence showed 2-yr CSM of 52.6% versus 77.7%, respectively, after CNT versus no CNT. CSM after CNT versus no CNT was invariably lower in all histologic subtypes and in contemporary patients. Multivariable competing-risks regression models predicting CSM favored CNT (hazard ratio [HR]: 0.38, confidence interval: 0.30–0.47, p < 0.001) in all patients and in all subgroups defined by histologic subtypes (HR: 0.14–0.43, all p ≤ 0.02), as well as in contemporary patients (HR: 0.32, p < 0.001). The ISB analyses yielded statistically significant and clinically meaningful CSM-free survival benefit of +3 mo after CNT versus no CNT in individuals with observed CSM-free survival ≤24 mo. The 2-yr CSM-free survival increased from baseline of 46.1% versus 19.4% (Δ = 26.7%, p < 0.001) to 70.3% versus 54.4% (Δ = 15.9%, p = 0.005) after CNT versus no CNT, in patients that survived 12 mo, respectively. Landmark analyses rejected bias favoring CNT. Data were retrospective. Conclusions: CSM is lower after CNT for non-ccmRCC in all histologic subtypes and in contemporary patients except for unproven ISB in collecting duct patients. This observation should encourage greater CNT consideration in non-ccmRCC. Patient summary: Cytoreductive nephrectomy appears to improve survival in metastatic non-clear cell renal cell carcinoma, but it is used infrequently. © 2017 European Association of Urology Cytoreductive nephrectomy reduces cancer-specific mortality in all histologic subtypes and in contemporary metastatic non-clear cell renal cell carcinoma patients; however, it might be performed too rarely.