Impact of smoking on resected lung cancer depends on epidermal growth factor receptor mutation.

Objectives: Smokers comprise the majority of surgical patients with primary lung cancer. Epidermal growth factor receptor (EGFR) mutation-negative status impacts the treatment of recurrence. However, the prognostic impact of cigarette smoking stratified by EGFR mutation status has not been reported. Therefore, we assessed its impact on patients with resected lung cancer.

Methods: We retrospectively analysed 362 consecutive patients who underwent complete resection for stage 1 primary lung cancer at our institution between 2012 and 2021. The EGFR mutation status was evaluated using the real-time polymerase chain reaction. We compared the overall survival (OS) and disease-free survival (DFS) between patients with and without a history of smoking.

Results: The EGFR mutation-negative group included 194 patients, of whom 160 (83%) had a history of smoking. Male sex (P < 0.01), forced expiratory volume in 1 s (P < 0.01) and adenocarcinoma (P < 0.01) showed significant differences between the groups. In the EGFR mutation-positive group, the 5-year OS and DFS were similar regardless of smoking status (OS: 86% vs 75%; DFS: 73% vs 73%). In the EGFR mutation-negative group, the 5-year OS and DFS were significantly poorer in the smoking group (OS: 87% vs 65%, P = 0.05; DFS: 84% vs 54%, P = 0.01). Deaths from other diseases were relatively high (n = 19, 53%).

Conclusions: Cigarette smoking may be associated with a poor prognosis in EGFR mutation-negative lung cancer but had no impact on the prognosis of the EGFR mutation-positive group. This finding underscores the potential influence of smoking on the treatment of lung cancer recurrence but also highlights its significance in contributing to death from other diseases.