Prognostic impact of epidermal growth factor receptor mutation in grade 3 stage IA lung adenocarcinomas

Stage IA adenocarcinomas (LUAD) with high-risk features exhibited an increased recurrence rate, and the role of adjuvant therapy in this population remains controversial. Our study aimed to evaluate the prognostic impact of epidermal growth factor receptor (EGFR) mutation in grade 3 stage IA LUAD.

Between 2016 and 2020, 483 consecutive patients undergoing operation, with grade 3 pathologic stage IA LUAD were evaluated. The Kaplan-Meier analysis was performed to assess recurrence-free survival (RFS) and overall survival (OS). Prognostic factors were evaluated using the Cox proportional hazards model.

An EGFR mutation was identified in 238 patients (49.3%), including 122 (51.3%) with an exon 19 deletion (Ex 19), 100 (42.0%) with an exon 21 L858R (Ex 21), and 16 (6.7%) with other EGFR mutations. The adjuvant chemotherapy was performed in 23 (4.8%) cases. EGFR mutant showed worse RFS than EGFR wild type (5-year RFS, 88.8% vs. 94.4%, p = 0.016). Subgroup analysis stratified by tumor size indicated that, among patients with pT1c tumors, EGFR mutant had a statistically lower 5-year RFS compared with EGFR wild type (n = 117; 83.1% vs. 96.2%; p = 0.036). Multivariable Cox regression analysis revealed that perineural invasion and EGFR mutation (HR = 2.095, 95%CI, 1.118 to 3.924) were independent predictors of worse RFS.

In grade 3 stage IA3 LUAD, the presence of an EGFR mutation was associated with a poorer prognosis compared with EGFR wild type. These findings underscore the potential need to explore tailored adjuvant treatment strategies in this subgroup.