Association between adjuvant EGFR-TKI therapy and survival outcomes in completely resected stage I invasive lung adenocarcinoma (≤3 cm) with sensitizing EGFR mutations and pathological high-risk features.
- 1Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
Abstract
Adjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy improves prognosis in patients with resected EGFR-mutated non-small cell lung cancer. However, evidence supporting its use in stage I disease with pathological high-risk features remains limited. We evaluated the association between adjuvant EGFR-TKI therapy and survival outcomes in patients with completely resected stage I invasive lung adenocarcinoma (LUAD) (≤3 cm), sensitizing EGFR mutations, and pathological high-risk features. This retrospective cohort study included patients who underwent complete resection for stage I invasive LUAD (≤3 cm) between January 2011 and May 2024. Eligible patients had an EGFR exon 19 deletion or exon 21 L858R mutation and at least one pathological high-risk feature, including lymphovascular invasion, visceral pleural invasion, spread through air spaces, high-grade histologic patterns (micropapillary, solid, and complex glandular patterns), or poor differentiation. The study outcomes were relapse-free survival (RFS) and overall survival (OS). The primary analysis used a 90-day landmark design, with baseline differences addressed using stabilized inverse probability of treatment weighting (IPTW). Survival distributions were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Simon-Makuch curves and time-dependent Cox regression analysis were additionally used to account for changes in treatment exposure over time. A 120-day landmark analysis was performed as a sensitivity analysis. Among 357 eligible patients, 354 remained alive and relapse-free at the 90-day landmark. Of these, 104 had initiated adjuvant EGFR-TKI therapy by the landmark, whereas 250 had not. In the unweighted landmark analysis, adjuvant EGFR-TKI therapy was associated with improved RFS (P=0.004; HR =0.27, 95% CI: 0.13-0.56). This association remained significant after IPTW adjustment (P=0.009; HR =0.28, 95% CI: 0.11-0.68). No significant difference in OS was observed in either the unweighted analysis (P=0.91; HR =0.93, 95% CI: 0.33-2.63) or the IPTW-weighted analysis (P=0.38; HR =1.34, 95% CI: 0.50-3.61). In the time-dependent analysis, EGFR-TKI exposure was associated with a lower hazard of relapse (P<0.001; HR =0.27, 95% CI: 0.14-0.52) but not with OS (P=0.49; HR =1.14, 95% CI: 0.41-3.19). The 120-day landmark sensitivity analysis yielded consistent results. In patients with completely resected stage I invasive LUAD (≤3 cm), sensitizing EGFR mutations, and pathological high-risk features, adjuvant EGFR-TKI therapy was associated with improved RFS, whereas no significant association with OS was observed.
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BibTeX
@article{cao2026association,
title = {{Association between adjuvant EGFR-TKI therapy and survival outcomes in completely resected stage I invasive lung adenocarcinoma (≤3 cm) with sensitizing EGFR mutations and pathological high-risk features.}},
author = {Jie Cao and Zhaokang Huang and Fang Qiu and Nan Chen and Zhiyu Peng and Zetao Liu and Xizhou Liao and Xiaorong Zong and Peidi Li and Chenglin Guo and Jiandong Mei and Lunxu Liu},
journal = {Translational lung cancer research},
year = {2026},
month = sep,
doi = {10.21037/tlcr-2026-0951},
url = {https://europepmc.org/article/MED/42999658},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Association between adjuvant EGFR-TKI therapy and survival outcomes in completely resected stage I invasive lung adenocarcinoma (≤3 cm) with sensitizing EGFR mutations and pathological high-risk features.
AU - Jie Cao
AU - Zhaokang Huang
AU - Fang Qiu
AU - Nan Chen
AU - Zhiyu Peng
AU - Zetao Liu
AU - Xizhou Liao
AU - Xiaorong Zong
AU - Peidi Li
AU - Chenglin Guo
AU - Jiandong Mei
AU - Lunxu Liu
PY - 2026
DA - 2026/09/24
JO - Translational lung cancer research
DO - 10.21037/tlcr-2026-0951
UR - https://europepmc.org/article/MED/42999658
AB - Adjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy improves prognosis in patients with resected EGFR-mutated non-small cell lung cancer. However, evidence supporting its use in stage I disease with pathological high-risk features remains limited. We evaluated the association between adjuvant EGFR-TKI therapy and survival outcomes in patients with completely resected stage I invasive lung adenocarcinoma (LUAD) (≤3 cm), sensitizing EGFR mutations, and pathological high-risk features. This retrospective cohort study included patients who underwent complete resection for stage I invasive LUAD (≤3 cm) between January 2011 and May 2024. Eligible patients had an EGFR exon 19 deletion or exon 21 L858R mutation and at least one pathological high-risk feature, including lymphovascular invasion, visceral pleural invasion, spread through air spaces, high-grade histologic patterns (micropapillary, solid, and complex glandular patterns), or poor differentiation. The study outcomes were relapse-free survival (RFS) and overall survival (OS). The primary analysis used a 90-day landmark design, with baseline differences addressed using stabilized inverse probability of treatment weighting (IPTW). Survival distributions were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Simon-Makuch curves and time-dependent Cox regression analysis were additionally used to account for changes in treatment exposure over time. A 120-day landmark analysis was performed as a sensitivity analysis. Among 357 eligible patients, 354 remained alive and relapse-free at the 90-day landmark. Of these, 104 had initiated adjuvant EGFR-TKI therapy by the landmark, whereas 250 had not. In the unweighted landmark analysis, adjuvant EGFR-TKI therapy was associated with improved RFS (P=0.004; HR =0.27, 95% CI: 0.13-0.56). This association remained significant after IPTW adjustment (P=0.009; HR =0.28, 95% CI: 0.11-0.68). No significant difference in OS was observed in either the unweighted analysis (P=0.91; HR =0.93, 95% CI: 0.33-2.63) or the IPTW-weighted analysis (P=0.38; HR =1.34, 95% CI: 0.50-3.61). In the time-dependent analysis, EGFR-TKI exposure was associated with a lower hazard of relapse (P<0.001; HR =0.27, 95% CI: 0.14-0.52) but not with OS (P=0.49; HR =1.14, 95% CI: 0.41-3.19). The 120-day landmark sensitivity analysis yielded consistent results. In patients with completely resected stage I invasive LUAD (≤3 cm), sensitizing EGFR mutations, and pathological high-risk features, adjuvant EGFR-TKI therapy was associated with improved RFS, whereas no significant association with OS was observed.
SN - 2218-6751
SN - 2226-4477
ER -