The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in the targeted therapy and immunological therapy era: a systematic review and meta-analysis

Background:The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) remains controversial. In addition, several unanswered questions regarding the use of CN remain: Can CN provide survival benefits for patients with mRCC? Where do we place CN in the treatment sequence paradigm among patients with mRCC? How do we best stratify patients with mRCC for CN therapy? Materials and Methods:A search strategy was conducted in the PubMed, Embase, and Web of Science databases. Studies were included only in the English language. The risk of bias assessment was made by using ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) and RoB 2 (Risk of Bias 2) tools. The expected outcomes were analyzed by meta-analyses with the fixed-effects model or random effects model, including overall survival (OS) and progression-free survival (PFS). The measure of effect was the hazard ratio (HR) with a 95% CI, and sensitivity analysis was conducted to assess the reliability of the final results. Results:A total of 30 studies were included in the qualitative analysis. The HR for OS was 0.55 (95% CI, 0.50-0.61), and PFS was 0.72 (95% CI, 0.66-0.80), favoring CN compared with no CN. The upfront CN plus targeted therapy (TT) group had superior OS (HR, 0.57; 95% CI, 0.51-0.64) compared with the TT alone group. Furthermore, upfront CN plus systemic therapy (ST) was associated with numerically inferior OS compared with ST plus deferred CN in patients with mRCC (HR, 1.31; 95% CI, 0.98-1.74). Finally, the leave-one-out test of sensitivity analysis indicated that the results of this meta-analysis were stable and reliable in the overall HR estimates for these survival outcomes. Conclusions:First, CN was associated with better survival than no CN in patients with mRCC. Second, the combination of upfront CN and TT may lead to superior survival outcomes compared to TT alone in patients with mRCC. Survival outcomes were similar between the upfront CN+ST group and the ST+deferred CN group in patients with mRCC. Exact patient selection based on baseline prognostic factors is needed to promise maximal survival for patients with mRCC.