Prognostic significance of sarcomatoid features in metastatic renal cell carcinoma treated with cytoreductive nephrectomy and targeted therapy

Introduction: The presence of sarcomatoid features in localized renal cell carcinoma (RCC) is associated with worse outcomes. We sought to use a national database to evaluate the outcomes and prognosis of metastatic RCC (mRCC) with sarcomatoid features treated with cytoreductive nephrectomy (CN) and targeted therapy (TT). Methods: The National Cancer Database (2010-2013) was used to identify patients with mRCC at diagnosis. Only patients who underwent CN followed by TT were included. Kaplan-Meier curves, log-rank test, and multivariate Cox regression analysis were used to compare overall survival (OS) between mRCC with and without sarcomatoid fea-tures. Subgroup analysis in patients with clear cell RCC (ccRCC) was performed. Results: A total of 1,427 patients with mRCC treated with CN followed by TT were included of which 364 (26%) had mRCC with sarcomatoid features. mRCC with sarcomatoid features were more likely to have Fuhrman grade 4 cancer. mRCC with sarcomatoid fea-tures had worse OS than mRCC without sarcomatoid features (24.6 vs 12.0 months, P < 0.001). For the clear cell cohort, mRCC with sarcomatoid features had worse OS than mRCC without sarcomatoid features (26.2 vs 14.0 months, P < 0.001). Multivariate Cox regression showed sarcomatoid features was significantly associated with worse OS in the overall cohort (hazard ratio [HR] =1.63, 95% confidence interval [CI] =1.38-1.91, P < 0.001) and the ccRCC subcohort (HR=1.53, 95% CI=1.23-1.90, P < 0.001). Discussion/Conclusion: mRCC with sarcomatoid features treated with CN and TT has a very poor and drastically different prognosis compared with mRCC without sarcomatoid features. With the expansion of systemic RCC therapies, investigation is needed to optimize treatment in this high-risk cohort.