Adjuvant therapy in pStage IA1–IIA lung adenocarcinoma (pN0): A multicenter study focusing on EGFR mutations and recurrence patterns (CReGYT-01 EGFR study)

Abstract

Background

Adjuvant treatment strategies based on EGFR mutation status remain unestablished in stage I–II lung adenocarcinoma. Although UFT is an established adjuvant therapy in Japan for resected pathological N0 (pN0) lung adenocarcinoma, its clinical utility according to EGFR mutation status remains unclear. This study aimed to evaluate the efficacy of UFT and recurrence patterns in pStage IA1–IIA disease, with a primary focus on pStage IA3–IIA and the influence of EGFR mutation status.

Methods

This multicenter retrospective study included 2,462 patients with pStage IA1–IIA lung adenocarcinoma (TNM 8th edition) who underwent complete resection at 21 institutions in Japan (2015–2018). Propensity score matching was employed to adjust for baseline differences between treatment groups. We evaluated the survival benefit of UFT by EGFR mutation status and analyzed recurrence patterns based on EGFR status and other clinicopathological variables.

Results

In the post-PSM cohort (N = 600), UFT significantly improved overall survival (OS) (p = 0.007, HR = 0.546), particularly in EGFR wild-type patients (p < 0.001, HR = 0.403). UFT also prolonged recurrence-free survival (RFS) in EGFR wild-type cases (p = 0.004, HR = 0.604). No OS or RFS benefit was observed in EGFR mutation-positive patients. Subgroup analysis showed that UFT provided significant OS benefit in patients with high-malignancy histological subtypes such as solid/micropapillary (HR = 0.32, 95 % CI: 0.13–0.80). EGFR mutation and lymphovascular invasion were independent predictors of recurrence, with EGFR mutations associated specifically with distant and CNS recurrence.

Conclusions

Adjuvant UFT improves OS and RFS in EGFR wild-type pStage IA3–IIA lung adenocarcinoma, particularly in patients with high-risk pathological features. In contrast, UFT is ineffective in EGFR mutation-positive cases, highlighting the need for refined adjuvant treatment strategies tailored to EGFR status and tumor biology in early-stage lung adenocarcinoma with pathological N0 (pN0).