Surgery is still the primary treatment for patients with early-stage, EGFR mutation-positive (EGFR-M+), non-small cell lung cancer (NSCLC), although tailored adjuvant medicines are increasingly being used to improve survival. Researchers’ goal was to determine prognostic markers for recurrence-free survival (RFS) in early-stage EGFR-M+ NSCLC patients to provide individualized adjuvant therapies. There were 2,340 patients diagnosed with non-squamous NSCLC at pathologic stage (pStage) IB-IIIA who underwent successful curative surgery between January 2008 and August 2020. About 1,181 patients with pStage IB-IIIA, common EGFR-M+ NSCLC who had surgical resection were examined for clinicopathologic risk variables. Genomic analysis was performed on a large sample size (56 patients and matched controls) to discover potential molecular risk factors (pStage II and IIIA and type of EGFR mutation). The Median follow-up duration was 38.8 months (0.5–156.2). Among 1,181 patients, pStage IB, II, and IIIA comprised 577 (48.9%), 331 (28.0%), and 273 (23.1%) subjects, respectively. The median RFS for pStage IB, II, and IIIA was 73.5 months (95% CI: 62.1-84.9), 48.7 months (95% CI: 41.2-56.3), and 22.7 months (95% CI: 19.4-26.0), respectively (P<0.001). Clinicopathologic characteristics related with RFS included pathologic cell of origin (type II pneumocyte-like tumor cell vs. bronchial surface epithelial cell-like tumor cell), micropapillary subtype, vascular invasion, and pleural invasion. Without regard to pStage II or IIIA, the RNA subtype with a non-terminal respiratory unit (non-TRU) was linked with a poor RFS (HR, 3.49; 95% CI, 1.72-7.09; P <0.01), as was a TP53 mutation (HR, 2.50; 95% CI, 1.24-5.04; P=0.01). Patients with a mutant signature for Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) had shorter progression-free survival after treatment with an EGFR-tyrosine kinase inhibitor (TKI) than those without the signature (8.6 vs. 28.8 months; HR, 4.16; 95% CI, 1.28-13.46; P = 0.02).
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