Prognosis of epidermal growth factor receptor-mutated stage I lung adenocarcinoma with radiologically solid features

OBJECTIVES The prognostic role of the epidermal growth factor receptor (EGFR) mutation remains controversial, especially in early-stage lung adenocarcinoma with a solid appearance. We evaluated the oncological outcomes of clinical stage I (c-stage I) radiologically invasive lung adenocarcinoma by EGFR mutation status. METHODS Between 2008 and 2013, the data from 463 surgically resected c-stage I radiologically invasive, i.e. solid-dominant lung adenocarcinomas subjected to EGFR mutant analysis, were evaluated. Oncological outcomes were assessed using multivariable Cox regression analysis. Recurrence-free survival (RFS) was estimated using Kaplan-Meier analysis and the log-rank test. RESULTS A total of 229 (49%) samples harboured the EGFR-mutant adenocarcinoma. Overall, the 5-year RFS did not differ significantly between the EGFR-mutant and EGFR wild-type groups (67.3% vs 64.9%; P = 0.639). However, among the clinical T1c/T2a tumour subset (n = 177), a multivariable Cox hazard model revealed that radiologically pure-solid tumour (P = 0.024), EGFR-mutant (P = 0.027) and pathological stage II/III (P < 0.001) were significant predictors of a poor RFS. Furthermore, in the c-T1c/T2a radiologically pure-solid lung adenocarcinoma subset, the EGFR-mutant group showed marginally lower 5-year RFS compared to that with the EGFR wild-type group (n = 134; 34.9% vs 53.0%; P = 0.062). Among them, multivariable Cox regression analysis revealed that EGFR mutant (P = 0.037) and pathological stage II/III (P = 0.011) were independently and significantly prognostic for worse RFS. CONCLUSIONS Among the c-stage I radiologically invasive lung adenocarcinomas, the EGFR mutation-positive type was correlated with an increased risk of recurrence in the c-T1c/T2a radiologically pure-solid tumour subset. When considering the prognostic value of EGFR mutations in early-stage lung adenocarcinoma, it is necessary to stratify them based on the presence of a ground-glass opacity component. Since the discovery of the epidermal growth factor receptor (EGFR) gene mutation [1, 2], it is well known that the EGFR gene mutation is one of the most frequent driver-oncogene alternations in non-small-cell lung cancer that leads to constitutive activation of the growth pathways driving tumourigenesis.

Automated summary

The study evaluated the prognostic role of EGFR mutation in early-stage invasive lung adenocarcinoma, finding that tumor subtype and pathological staging were predictive factors for recurrence-free survival. In the subset of clinical T1c/T2a lung adenocarcinomas, EGFR mutation and advanced pathological staging independently predicted worse RFS.