Rare epidermal growth factor receptor (EGFR) mutations in completely resected stage I lung adenocarcinoma: a real-world study of mutation spectrum, clinicopathological features, and prognosis.
- 1Department of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan University, Chengdu, China.
Abstract
Rare epidermal growth factor receptor (EGFR) mutations are heterogeneous, and their significance after complete resection of stage I lung adenocarcinoma (LUAD) remains unclear. We evaluated the mutation spectrum, clinicopathological correlates, postoperative recurrence patterns, and survival outcomes of a study-defined primary rare EGFR mutation cohort after predefined exclusion of isolated T790M, exon 20 insertion-only disease, and major driver co-alterations. Consecutive patients who underwent R0 resection for pathological stage I LUAD with postoperative EGFR testing at West China Hospital between 2011 and 2024 were retrospectively identified. Rare mutation subtypes, compound mutation patterns, recurrence-free survival (RFS), and overall survival (OS) were assessed. Prognostic factors were evaluated using Cox regression, and outcomes were compared with classical EGFR mutations using 1:2 propensity score matching (PSM). Among 1,357 EGFR-positive stage I LUADs, 176 patients formed the primary rare-mutation cohort. The most frequent rare mutation groups were G719X (n=104), L861Q (n=71), and S768I (n=24), with distinct compound mutation patterns. Five-year OS and RFS were 95.8% and 93.5%, respectively. A micropapillary component was associated with shorter RFS in the primary multivariable model [hazard ratio (HR) =4.062, 95% confidence interval (CI): 1.134-14.544; P=0.03]. The unweighted number of pathological high-risk features was associated with RFS (global log-rank P=0.039), whereas adjuvant systemic therapy among stage IB patients and compound rare mutation status were not significantly associated with RFS. After PSM under comparable observed postoperative management, the rare-mutation group had similar OS and a lower recurrence risk than the classical-mutation group. After exclusion of isolated T790M and exon 20 insertion-only disease, completely resected stage I LUAD with rare EGFR mutations showed favorable long-term outcomes. Compared with classical mutations, rare mutations were associated with lower recurrence risk and similar OS after treatment-balanced matching. Pathological features, particularly a micropapillary component, may help identify patients at higher risk of recurrence.
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BibTeX
@article{man2026rare,
title = {{Rare epidermal growth factor receptor (EGFR) mutations in completely resected stage I lung adenocarcinoma: a real-world study of mutation spectrum, clinicopathological features, and prognosis.}},
author = {Lajie Man and Liang Xia and Chuan Li and Xiaohu Hao and Xiaolong Zhang and Ruichen Cui and Chenglin Guo and Yafei Xie and Jiahan Cheng and Chengwu Liu and Lunxu Liu},
journal = {Translational lung cancer research},
year = {2026},
month = oct,
doi = {10.21037/tlcr-2026-0953},
url = {https://europepmc.org/article/MED/42999644},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Rare epidermal growth factor receptor (EGFR) mutations in completely resected stage I lung adenocarcinoma: a real-world study of mutation spectrum, clinicopathological features, and prognosis.
AU - Lajie Man
AU - Liang Xia
AU - Chuan Li
AU - Xiaohu Hao
AU - Xiaolong Zhang
AU - Ruichen Cui
AU - Chenglin Guo
AU - Yafei Xie
AU - Jiahan Cheng
AU - Chengwu Liu
AU - Lunxu Liu
PY - 2026
DA - 2026/10/15
JO - Translational lung cancer research
DO - 10.21037/tlcr-2026-0953
UR - https://europepmc.org/article/MED/42999644
AB - Rare epidermal growth factor receptor (EGFR) mutations are heterogeneous, and their significance after complete resection of stage I lung adenocarcinoma (LUAD) remains unclear. We evaluated the mutation spectrum, clinicopathological correlates, postoperative recurrence patterns, and survival outcomes of a study-defined primary rare EGFR mutation cohort after predefined exclusion of isolated T790M, exon 20 insertion-only disease, and major driver co-alterations. Consecutive patients who underwent R0 resection for pathological stage I LUAD with postoperative EGFR testing at West China Hospital between 2011 and 2024 were retrospectively identified. Rare mutation subtypes, compound mutation patterns, recurrence-free survival (RFS), and overall survival (OS) were assessed. Prognostic factors were evaluated using Cox regression, and outcomes were compared with classical EGFR mutations using 1:2 propensity score matching (PSM). Among 1,357 EGFR-positive stage I LUADs, 176 patients formed the primary rare-mutation cohort. The most frequent rare mutation groups were G719X (n=104), L861Q (n=71), and S768I (n=24), with distinct compound mutation patterns. Five-year OS and RFS were 95.8% and 93.5%, respectively. A micropapillary component was associated with shorter RFS in the primary multivariable model [hazard ratio (HR) =4.062, 95% confidence interval (CI): 1.134-14.544; P=0.03]. The unweighted number of pathological high-risk features was associated with RFS (global log-rank P=0.039), whereas adjuvant systemic therapy among stage IB patients and compound rare mutation status were not significantly associated with RFS. After PSM under comparable observed postoperative management, the rare-mutation group had similar OS and a lower recurrence risk than the classical-mutation group. After exclusion of isolated T790M and exon 20 insertion-only disease, completely resected stage I LUAD with rare EGFR mutations showed favorable long-term outcomes. Compared with classical mutations, rare mutations were associated with lower recurrence risk and similar OS after treatment-balanced matching. Pathological features, particularly a micropapillary component, may help identify patients at higher risk of recurrence.
SN - 2218-6751
SN - 2226-4477
ER -