Differential Prognostic Value of Vascular Invasion in Resected Lung Adenocarcinomas According to Epidermal Growth Factor Receptor Mutational Status

It is unclear whether all patients with stage IB to IIIA epidermal growth factor receptor (EGFR)-mutant adenocarcinoma should receive adjuvant osimertinib. We investigated the prognostic value of vascular invasion for risk stratification according to EGFR mutational status. This retrospective study evaluated patients with stage IB to IIIA lung adenocarcinoma resected between 2011 and 2016 at a tertiary care center. The study outcome was overall survival (OS). The prognostic value of vascular invasion was analyzed using the adjusted log-rank test and multivariable Cox regression with clinico-pathological factors as covariates. A sensitivity analysis, which included the presence of ground-glass opacity on CT scans as an additional covariate, and subgroup analyses according to the pathological stage were performed. In total, 272 patients were included (146 women; median age, 66 years [interquartile range: 58, 72 years]; 128 EGFR-mutant adenocarcinomas). The 5-year OS rate was 90.8% (95% CI: 84.0%, 98.1%) in EGFR-mutant, vascular invasion-absent lung adenocarcinomas, which was higher than in other subgroups (P < .05). Vascular invasion was an independent, negative prognostic factor in EGFR-mutant lung adenocarcinomas (adjusted log-rank test, P = .02; adjusted hazard ratio, 3.01; 95% CI: 1.30, 7.02; P = .01). However, the prognosis of EGFR wild-type adenocarcinomas was not associated with the presence of vascular invasion (adjusted log-rank test, P = .95; adjusted hazard ratio, 1.32; 95% CI: 0.74, 2.34; P = .35). Similar results were observed in the sensitivity analysis and subgroup analyses. Vascular invasion-absent, EGFR-mutant, resected lung adenocarcinomas showed a very good prognosis, and vascular invasion had a differential prognostic value according to EGFR mutational status. Risk stratification in early-stage, EGFR-mutant lung adenocarcinomas would enable fine-tuning of the adjuvant osimertinib candidates. We identified vascular invasion as a negative prognostic factor that can stratify overall survival (OS) in stage IB to IIIA, EGFR-mutant lung adenocarcinomas. The prognostic association of vascular invasion with OS, observed in EGFR-mutant adenocarcinomas, was not found in EGFR wild-type adenocarcinomas.