Should CARMENA Really Change our Attitude Towards Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma? A Systematic Review and Meta-Analysis Evaluating Cytoreductive Nephrectomy in the Era of Targeted Therapy

Background: Cytoreductive nephrectomy in metastatic renal cell carcinoma (mRCC) patients has been common clinical practice due to evidence that resection of the primary tumor results in a survival benefit regardless of systemic treatment. Recently, the first large phase III randomized, non-inferiority prospective clinical trial evaluating this surgical approach demonstrated that systemic treatment alone was not inferior to primary surgery plus systemic treatment. Objective: Our aim was to evaluate if cytoreductive nephrectomy results in a survival benefit over systemic treatment alone in patients with mRCC and in specific subgroups, including patients with brain metastases, poor performance status, poor prognosis according to IMDC or MSKCC criteria, and clear cell and non-clear cell histologies. Patients and Methods: We identified 16 published studies providing complete data for the comparison between cytoreductive nephrectomy + systemic treatment versus systemic treatment alone, and selected 9 for subgroup analysis. The inverse variance technique was applied for the meta-analysis of hazard ratios (HR), and, due to the intrinsic heterogeneity of the data, we adopted a random effects model. Risk of bias among the studies was estimated by the Newcastle-Ottawa Scale (NOS). Results: Our analysis suggested a survival benefit for patients receiving cytoreductive nephrectomy (pooled HR of 0.48, 95% confidence interval of 0.42–0.56) in the overall population. Survival advantages were also observed in patients with clear cell and non-clear renal cell carcinoma, while no benefit was evident in patients with brain metastasis, poor performance status, and poor risk. Conclusion: Cytoreductive nephrectomy seems to result in a survival benefit in both clear cell and non-clear cell histology, while no survival advantage was found in patients with specific clinical features. Despite a high level of heterogeneity, our results highlight the importance of a good selection of patients to whom a primary surgical approach could be proposed.