Position of cytoreductive nephrectomy in the setting of metastatic renal cell carcinoma patients: does the CARMENA trial lead to a paradigm shift?

Introduction > The role of cytoreductive nephrectomy (CN) in combination with targeted therapy has been debated after the results of the CARMENA trial. We decided to reassess the available evidence on the setting of CN in metastatic renal cell carcinoma (mRCC) patients. Methods > Critical review of the literature focusing on CN in mRCC patients. Results > Previous trials demonstrated a survival benefit of CN during the cytokine-era. In the targeted therapies-era, retrospective studies has confirmed the survival benefit of CN but presented inherent selection biases. Recently, the CARMENA trial showed that sunitinib alone was not inferior to CN plus sunitinib, and could be followed by subsequent CN in good-responders patients. CN is found to be a morbid surgery (perioperative mortality rate of 0-13% and major postoperative complications rate of 3-36%) and should be avoided in patients with primary refractory disease, using targeted therapy as a selection tool. Some parameters have been associated with shorter overall survival, leading to propose up-front CN only to patients with good performance status, a high-volume renal tumor and a low metastatic burden. Conclusions > While previous studies demonstrated a survival benefit of CN, the CARMENA trial showed that immediate CN was not necessary in some patients with mRCC, leading to a paradigm shift. Targeted therapy should be proposed as first line treatment, and the response to pre-surgical therapy could be used as a selection tool for subsequent decision of CN in good-responders patients.