Longitudinal Analysis of Recurrence and Risk Factors of Early-Stage Resected Adenocarcinoma With Common EGFR Mutations: A Multicenter Retrospective Cohort Study in South Korea

Abstract

Introduction: Despite curative surgery for lung cancer, 30% to 55% of patients experience recurrence or death, which highlights the importance of adjuvant treatment. Adjuvant osimertinib therapy effectively prolongs disease-free and overall survival in patients with lung cancer harboring common epidermal growth factor receptor (EGFR) mutations. To identify potential candidates for adjuvant osimertinib, it is crucial to understand the rates and identify risk factors of recurrence. Methods: This multicenter, retrospective cohort study was conducted in the Republic of Korea and enrolled patients who, between 2010 and 2017, underwent resection of stages I-III adenocarcinomas, with common EGFR mutations. The primary outcomes comprised the rate and risk factors of postoperative recurrence. Results: Among the 759 participants, the overall recurrence rate and median recurrence-free survival were 39.1% and 59.8 (interquartile range [IQR], 26.3-84.2) months, respectively, during a median follow-up of 73.0 (IQR, 55.4-95.0) months. The recurrence rates for stages IA, IB, IIA, IIB, IIIA, and IIIB were 14.7%, 45.5%, 53.8%, 72.5%, 80.3%, and 93.3%, respectively. Multivariate analysis revealed that age ≥ 65 years, body mass index < 18.5 kg/m², the Del19 subtype of EGFR mutation, tumor size ≥ 2.3 cm, N1 involvement, N2 involvement, predominantly micropapillary or solid pattern, and the presence of visceral pleural invasion were independently associated with recurrence. Conclusion: This multicenter cohort study demonstrated that stages I-III EGFR-mutated adenocarcinoma has a postoperative recurrence rate of 39.1%, and identified 7 independent risk factors for recurrence. © 2025 The Author(s)