Cytoreductive nephrectomy for synchronous metastatic renal cell carcinoma. Is there enough evidence?

Objective: To assess the role of Cytoreductive Nephrectomy for synchronous metastatic Renal Cell Carcinoma patients in the Systemic Therapy era and beyond regarding the Overall Survival, the optimal sequence between Systemic Therapy and Cytoreductive Nephrectomy and prognostic factors. Methods: The systematic review was conducted in accordance with the PRISMA guidelines. Bibliographic search was performed in Medline (PubMed), ClinicalTrials.gov, and Cochrane Library-Cochrane Central Register of Controlled Trials (CENTRAL). Studies included were those indexed from 2005 in an attempt to limit those conducted in the cytokine era. Risk of bias assessment was performed by two authors (K.S and T.L) using the Cochrane Collaborative Risk of Bias tool for randomized trials, the Cochrane Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for nonrandomized studies. Results: Cytoreductive nephrectomy was associated with improved overall survival in all but one of the observational studies. While in all of these studies the unvariable analysis showed improved overall survival in favor of the cytoreductive nephrectomy group in some studies the subgroup analysis showed no benefit. Regarding the optimal sequence, deferred cytoreductive nephrectomy demonstrated better results in more studies than upfront cytoreductive nephrectomy but a advantage was not clearly certain. In the analysis of possible prognostic factors for overall survival with cytoreductive nephrectomy, most common prognostic factors found were age (in 8 studies), tumor histology (in 7 studies), number of metastasis (in 6 studies), and T stage. Conclusions: Cytoreductive nephrectomy can still play an important role in wisely selected patients, although the role of cytoreductive nephrectomy in the new immunotherapy era needs to be defined.