Increased risk of recurrence in resected EGFR-positive pN0M0 invasive lung adenocarcinoma

Abstract

Background: This study was conducted to evaluate the prognostic and recurrent impact of EGFR mutation status in resected pN0M0 lung adenocarcinoma with consideration of the histological subtype.

Methods: Following retrospective analysis of whole 474 consecutive pathological N0M0 lung adenocarcinoma patients, the prognostic significance of EGFR mutation status was evaluated in limited 394 subjects. Overall survival and recurrence-free interval (RFI) were estimated using the Kaplan-Meier method and compared using a log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazard models.

Results: The five-year RFI was 85.7% and 93.3% for EGFR positive (n = 176) and negative (n = 218) cases, respectively (hazard ratio [HR] 1.992, 95% confidence interval [CI] 1.005-3.982; P = 0.048). Following the exclusion of specific subtypes free from recurrence or EGFR mutation (adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive mucinous adenocarcinoma), the five-year RFI was obviously poorer in EGFR positive compared to negative cases (80.7% and 92.1%, respectively; HR 2.163, 95% CI 1.055-4.341; P = 0.035). Multivariate analysis excluding the specific subtypes confirmed that male sex, age, current or Ex-smoking status, pleural invasion, and EGFR-positive status were independently associated with shorter RFI. No significant differences in five-year overall survival were found between the EGFR mutation positive and negative groups (88.7% and 93.7%, respectively; HR 1.630, 95% CI 0.787-3.432; P = 0.2).

Conclusion: EGFR mutations are associated with recurrence in pN0M0 lung adenocarcinoma. EGFR mutation status and histological subtype should be considered when evaluating the risk of recurrence in resected lung adenocarcinoma patients.

Keywords: EGFR mutation; histological subtype; lung adenocarcinoma; recurrence; surgery.