Adjuvant Systemic Treatment for Renal Cancer After Surgery: A Network Meta-Analysis

Background Approximately 15% to 20% of patients will experience disease recurrence following surgical removal of renal cell carcinoma. A range of pharmacological agents is prescribed for metastatic renal cell carcinoma, but there are trials testing whether these have an earlier role in the adjuvant setting. We aim to assess the efficacy of adjuvant systemic treatment following surgery in patients with renal cell carcinoma and to determine the most effective treatment. Methods The protocol for this review was published in PROSPERO (CRD42021281588). We searched multiple databases up to August 2021. We included only randomized trials of patients with renal cell carcinoma that had been completely resected. We included patients with locoregional nodal disease if it was surgically removed, and excluded all cases of metastatic disease. We included all adjuvant systemic therapies that were commenced within 90 days of renal surgery. A network meta-analysis was performed using a frequentist approach. Results A total of 13 studies with 8103 patients were included for analysis. Only pembrolizumab (HR 0.74; 95%CI 0.57 to 0.96) and pazopanib (HR 0.80; 95%CI 0.68 to 0.95) improved disease-free survival compared with observation. These 2 treatments were the 2 highest ranked comparisons with a P-score of 0.87 and 0.80. No agent improved overall survival. All agents increased the risk of severe adverse events compared with observation. Conclusions Pembrolizumab and pazopanib were the only 2 adjuvant agents that improved time to disease recurrence compared with observation, with the former likely being the more efficacious. None of the treatments improved overall survival and almost all increased severe adverse events. Introduction