Introduction: Despite surgical resection, many patients with high-risk renal cell carcinoma (RCC) experience recurrence. Following approvals in metastatic RCC, there has been interest in using immune checkpoint inhibition (ICI) in the adjuvant setting. The objective of this study is to synthesize available data regarding the disease-free survival (DFS) benefit of adjuvant ICIs for patients with RCC and evaluate the overall safety profile of ICIs in this setting. Methods: PubMed, Embase, and relevant conference proceedings were searched from inception up to September 18, 2022. Phase III randomized controlled trials (RCTs) comparing adjuvant ICI versus placebo/observation were included. Study screening and selection, along with data extraction was performed in duplicate according to a predefined registered protocol. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline and the Cochrane Collaboration’s tool for assessing risk of bias were used. All outcomes were analyzed using random-effects meta-analysis owing to interstudy heterogeneity. Sensitivity and subgroup analyses were performed to identify potential sources of heterogeneity. The primary outcome of interest was DFS. Variables for subgroup analyses were PD-L1 expression, sarcomatoid features, nephrectomy type, and disease-risk category. Secondary outcomes included grade =3 adverse events (AEs), immune-related AEs, and treatment discontinuation due to AEs. Results: Among the four included studies, one demonstrated a significant DFS benefit. There was considerable clinical and statistical heterogeneity (I2=64%) due to differences in inclusion criteria and interventions. While pooled results across the four studies did not demonstrate a significant benefit in DFS overall (HR 0.85, 95% CI 0.69-1.04), there was significant benefit among patients with positive PD-L1 expression (HR 0.72, 95% CI 0.55-0.94) or sarcomatoid features (HR 0.59, 95% CI 0.38-0.91). Conclusions: The evidence base to date regarding ICI as adjuvant therapy in RCC is mixed – conclusions are limited by considerable heterogeneity between studies. However, pooled analyses suggest that patients with positive PD-L1 expression or sarcomatoid features are most likely to benefit from adjuvant immunotherapy. SOURCE OF Funding: None
