Abstract： Background:The metastatic renal cell carcinoma (mRCC) patients treated with upfront cytoreductive nephrectomy combined with α-interferon yields additional overall survival (OS) benefits.It is unclear whether mRCC patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) will benefit from such cytoreductive nephrectomy either.The aim of the study was to identify variables for selection of patients who would benefit from upfront cytoreductive nephrectomy for mRCC treated with VEGFR-TKI.Methods:Clinical data on 74 patients enrolled in 5 clinical trials conducted in Cancer Hospital (Institute),Chinese Academy of Medical Sciences from January 2006 to January 2014 were reviewed retrospectively.The survival analysis was performed by the Kaplan-Meier method.Comparisons between patient groups were performed by Chi-square test.A Cox regression model was adopted for analysis of multiple factors affecting survival,with a significance level of α =0.05.Results:Fifty-one patients underwent cytoreductive nephrectomy followed by targeted therapy (cytoreductive nephrectomy group) and 23 patients were treated with targeted therapy alone (noncytoreductive nephrectomy group).The median OS was 32.2 months and 23.0 months in cytoreductive nephrectomy and noncytoreductive nephrectomy groups,respectively (P =0.041).Age ≤45 years (P =0.002),a low or high body mass index (BMI ＜19 or ＞30 kg/m2) (P =0.008),a serum lactate dehydrogenase (LDH) concentration ＞ 1.5 × upper limit of normal (P =0.025),a serum calcium concentration ＞1 0 mg/ml (P =0.034),and 3 or more metastatic sites (P =0.023) were independent preoperative risk factors for survival.The patients only with 0-2 risk factors benefited from upfront cytoreductive nephrectomy in terms of OS when compared with the patients treated with targeted therapy alone (40.0 months vs.23.2 months,P =0.042),while those with more than 2 risk factors did not.Conclusions:Five risk factors (age,BMI,LDH,serum calcium,and number of metastatic sites) seemed to be helpful for selecting patients who would benefit from undergoing upfront cytoreductive nephrectomy.