Renin-angiotensin system inhibitors and survival in patients with renal cell carcinoma: Evidence from a meta-analysis

Urol Oncol. 2025 Jun 20:S1078-1439(25)00212-1. doi: 10.1016/j.urolonc.2025.05.015. Online ahead of print.

Abstract

Background: The therapeutic potential of renin-angiotensin system inhibitors (RASi) in renal cell carcinoma (RCC) remains controversial. This meta-analysis synthesizes existing evidence to elucidate the association between RASi use and survival outcomes in RCC patients.

Methods: We conducted a systematic search of PubMed, Scopus, and Embase up to November 12, 2024, to identify studies that compared survival outcomes between users and non-users of RASi. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) were calculated using random-effects models. Subgroup analyses stratified by disease stage, treatment modality, and the type of RASi were performed.

Results: A total of 1,263 records were initially screened. Twelve retrospective studies, encompassing 22 cohorts and a combined total of 22,630 patients, were included in the final analysis. The pooled analysis revealed that RASi use was significantly associated with improved OS (HR, 0.74; 95% CI, 0.62-0.88) and PFS (HR, 0.74; 95% CI, 0.62-0.89). Notably, in patients with metastatic disease, the use of RASi was linked to an even greater enhancement in OS (HR, 0.71; 0.58-0.87) and PFS (HR, 0.72; 95%CI, 0.60-0.87). Subgroup analyses stratified by treatment modality indicated concurrent use of RASi with targeted therapy (HR, 0.69; 95% CI, 0.55-0.88) and immunotherapy (HR 0.55; 95% CI, 0.35-0.88) was associated with significantly improved OS.

Conclusion: This meta-analysis suggests RASi as a potential adjunctive therapy in RCC management, particularly in patients with metastatic disease, and those who receive targeted therapy or immunotherapy. These findings highlight the potential therapeutic benefit of RASi in the management of RCC and warrant further investigation to establish its role in clinical practice guidelines.

Keywords: Evidence; Meta-analysis; Renal cell carcinoma; Renin-angiotensin system inhibitors; prognosis.