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.