Pathological high-risk feature count and survival outcomes in patients with stage I invasive lung adenocarcinoma (≤3 cm): a retrospective cohort study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Pathological high-risk features in early-stage lung adenocarcinoma (LUAD) are associated with prognosis, but whether the number of coexisting features is associated with progressively worse prognosis remains uncertain. This study aimed to evaluate the prognostic impact of pathological high-risk feature count in patients with stage I invasive LUAD (≤3 cm). Methods: This retrospective cohort study included patients with stage I invasive LUAD (≤3 cm) who underwent complete resection between January 2018 and April 2025. Patients were stratified by the number of pathological high-risk features [lymphovascular invasion, visceral pleural invasion, spread through air spaces, high-grade histologic patterns (micropapillary, solid, and complex glandular patterns), and poor differentiation]. Relapse-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariable Cox regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among 4,030 patients, 2,791, 690, 296, and 253 had 0, 1, 2, and ≥3 pathological high-risk features, respectively. The median follow-up duration was 38 months for RFS and 39 months for OS. In the primary analysis, RFS was significantly worse for 1 versus 0 feature (log-rank P<0.001; HR =2.871; 95% CI: 1.720-4.794) and for ≥3 versus 2 features (log-rank P<0.001; HR =2.997; 95% CI: 1.655-5.429), but not for 2 versus 1 feature (log-rank P=0.37; HR =1.264; 95% CI: 0.674-2.370). For OS, the difference between the 1-feature and 0-feature groups remained significant (log-rank P=0.002; HR =2.309; 95% CI: 1.190-4.480), whereas the comparisons of 2 versus 1 feature (log-rank P=0.06; HR =1.885; 95% CI: 0.883-4.023) and ≥3 versus 2 features (log-rank P=0.15; HR =1.542; 95% CI: 0.756-3.144) were not significant. In the sensitivity analysis combining high-grade histologic patterns and poor differentiation, RFS was significantly worse across all adjacent groups: 1 versus 0 feature (log-rank P<0.001; HR =2.908; 95% CI: 1.769-4.781), 2 versus 1 feature (log-rank P=0.003; HR =1.985; 95% CI: 1.200-3.285), and ≥3 versus 2 features (log-rank P<0.001; HR =2.438; 95% CI: 1.404-4.234). For OS, significant differences were observed for 1 versus 0 feature (log-rank P<0.001; HR =2.548; 95% CI: 1.363-4.762) and 2 versus 1 feature (log-rank P=0.03; HR =1.950; 95% CI: 1.018-3.738), but not for ≥3 versus 2 features (log-rank P=0.09; HR =1.499; 95% CI: 0.716-3.137). Conclusions: A higher pathological high-risk feature count was associated with progressively worse prognosis in patients with stage I invasive LUAD (≤3 cm).
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223871571