EGFR Mutations and Recurrence Outcomes in Resected Non-Small Cell Lung Cancer: An Updated 2015-2025 Systematic Review and Meta-Analysis.

Abstract

The prognostic significance of EGFR mutations in resected non-small cell lung cancer (NSCLC) remains uncertain despite their established predictive value in advanced disease. We assessed the prognostic impact of EGFR mutation status on recurrence and disease-free survival (DFS) in resected stage I-III NSCLC. In this systematic review and meta-analysis, we searched PubMed, Embase, and Cochrane Library to identify studies of resected stage I-III NSCLC reporting recurrence or DFS according to EGFR status. Pooled recurrence rates, risk ratio (RR), and hazard ratio (HR) were calculated using random-effects models. Subgroup analyses were conducted by stage, recurrence site, mutation subtype, and adjuvant treatment. A total of 20 studies (4 randomized controlled trials and 16 retrospective observational studies), comprising 12 123 patients (7203 EGFR-mutant and 4920 wild-type), were included. Four studies focused on stage I disease, five on stage II-III, and eleven across stage I-III. The pooled recurrence RR comparing EGFR-mutant and wild-type tumors was 1.04 (95% CI, 0.88-1.23), and the pooled DFS HR was 1.07 (95% CI, 0.84-1.37), indicating no significant difference. Recurrence patterns were comparable, with no differences in local or distant relapse and only a modest, non-significant increase in central nervous system recurrence. Among EGFR-mutant tumors, adjuvant EGFR-TKIs improved DFS (HR 0.45, 95% CI, 0.29-0.71) unlike chemotherapy (HR 1.05, 95% CI, 0.67-1.66). EGFR mutation status is not associated with recurrence, DFS, or recurrence patterns in resected NSCLC. Adjuvant EGFR-TKIs, but not chemotherapy, confer significant DFS benefit, supporting their use as standard postoperative therapy.