Renin–angiotensin system inhibitor use and survival outcomes in lung cancer: a systematic review and meta-analysis

Background Renin-angiotensin system inhibitors (RASi) have been associated with favorable survival outcomes across various cancers, but their association with survival in lung cancer remains uncertain. We conducted a systematic review and meta-analysis to evaluate the association between RASi use and survival outcomes in patients with lung cancer. Methods PubMed and Embase were searched from inception to 6 July 2026. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup and sensitivity analyses, including large-study restricted analysis and precision-effect test and precision-effect estimate with standard error (PET-PEESE) regression, were performed to explore heterogeneity and assess the potential influence of small-study effects. Results Twenty-six studies involving 403,423 patients were included. RASi use was associated with longer overall survival (OS; HR = 0.76, 95% CI: 0.70–0.83; I 2 = 82.9%) and progression-free survival (PFS; HR = 0.79, 95% CI: 0.70–0.89; I 2 = 40.9%) in conventional random-effects meta-analyses. Subgroup analyses generally showed consistent associations across treatment modalities and geographic regions, although substantial heterogeneity remained in several subgroups. Egger’s test indicated small-study effects for OS. Although the large-study restricted analysis remained significant (HR = 0.82, 95% CI: 0.74–0.90), PET-PEESE adjustment attenuated the estimate to the null (HR = 1.00, 95% CI: 0.95–1.05). No significant evidence of small-study effects was observed for PFS. Conclusion Conventional meta-analysis showed an association between RASi use and longer OS and PFS. However, the OS association was attenuated to the null after adjustment for small-study effects, indicating that the magnitude and robustness of the observed OS association remain uncertain. These findings should therefore be interpreted cautiously and require confirmation in well-designed prospective studies. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251053671 , identifier: CRD420251053671.