Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis of Individual Patient Data

Background and objective: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors (ICIs) is controversial. We aimed to investigate the survival benefit of CN in patients with mRCC treated with ICIs.

Methods: We searched the EMBASE, MEDLINE, and Web of Science databases up to August 26, 2023 to identify studies comparing overall survival (OS) for patients with mRCC treated with ICIs with or without CN. We reconstructed individual patient data using published Kaplan-Meier curves and performed one- and two-stage meta-analyses using 6-mo and 12-mo landmarks to control for immortal time bias. We also performed subgroup analyses for patients treated with first-line ICI or upfront CN.

Key findings and limitations: We identified eight eligible studies involving a total of 2319 patients. There were statistically significant differences in baseline characteristics (age, clear cell histology, International mRCC Database Consortium scores) between the ICI + CN and ICI-alone groups. Combined CN + ICI therapy was associated with superior OS in the primary analysis (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.37-0.54) and secondary analyses, and in subgroup analyses for patients receiving first-line ICI therapy (HR 0.39, 95% CI 0.30-0.48) and upfront CN (HR 0.52, 95% CI 0.40-0.69).

Conclusions and clinical implications: CN combined with ICI therapy in mRCC may be associated with superior OS. Further studies are needed to confirm this finding and identify the patients most likely to benefit from CN in this setting.

Patient summary: We compared outcomes after immune checkpoint inhibitor (ICI) therapy, which boosts the immune system to fight cancer, with or without nephrectomy (surgical removal of the kidney) in patients with metastatic kidney cancer. We found that the combination of nephrectomy and ICI therapy was associated with better survival than just ICI therapy.