Prognostic value of epidermal growth factor receptor gene mutation in resected lung adenocarcinoma

Background: Mutation of the EGFR gene is known as a predictor for the response to EGFR tyrosine kinase inhibitor. Although EGFR mutation status is proposed to be incorporated in the Ninth Edition of the Lung Cancer Staging system, its prognostic value for surgically resected lung adenocarcinoma remains controversial. Methods: Data on 1512 patients with completely resected lung adenocarcinoma who underwent EGFR mutation analysis between 2008 and 2015 were collected. The prognostic value of EGFR mutations was determined in patients with lung adenocarcinoma stratified by clinicopathologic and radiologic characteristics. Independent prognostic factors were identified by multivariate analysis using the Cox proportional hazards model. Competing risk model was used to estimate the cumulative incidence. Results: EGFR mutations were identified in 935 patients (61.8%). In the entire cohort, there was no difference in recurrence-free survival between the EGFRmutated group and the wild-type group (P = .266). However, Cox multivariate analyses revealed that EGFR mutation was a strong independent prognostic factor for worse recurrence-free survival in patients with radiologic solid tumors (hazard ratio, 1.485; 95% confidence interval, 1.208-1.826; P<.001), histologic acinar patternpredominant adenocarcinoma/papillary pattern-predominant adenocarcinoma/ invasive mucinous adenocarcinoma (hazard ratio, 1.684; 95% confidence interval, 1.330-2.132; P<.001), and pathologic stage II and III (hazard ratio, 1.417; 95% confidence interval, 1.115-1.801; P = .004). Patients with EGFR mutations developed significantly more brain (hazard ratio, 1.827; 95% confidence interval, 1.213-2.766; P = .004) and bone (hazard ratio, 1.724; 95% confidence interval, 1.131-2.631; P = .011) metastases compared with the wild-type cohort. Conclusions: EGFR mutation was a strong poor prognostic factor in patients with radiologic solid, histologic acinar pattern-predominant adenocarcinoma/papillary pattern-predominant adenocarcinoma/invasive mucinous adenocarcinoma, and pathologic stage II and III lung adenocarcinomas. After surgery, distinct metastatic patterns were revealed according to EGFR mutation status. These findings have implications for the upcoming new lung cancer staging system.