Prognostic determinants in occult N1 non-small cell lung cancer after anatomical resection

Background: Clinically occult pN1 disease in non-small cell lung cancer (NSCLC) represents postoperative nodal upstaging, but prognostic factors within this subgroup remain incompletely defined. This study evaluated clinicopathological factors associated with disease-free survival (DFS) and overall survival (OS) in clinically node-negative NSCLC patients found to have pathological N1 disease after anatomical resection. Methods: Between January 2008 and November 2024, 94 patients with primary NSCLC who had been classified as clinically node-negative before surgery were retrospectively identified. All underwent anatomical lung resection and were subsequently found to have pathological N1 disease on definitive histopathological examination. DFS and OS were evaluated according to N1 nodal burden, final pathological stage, pleural invasion, nodal location, and other clinicopathological variables. Results: Of the 94 patients, 75 (79.8%) had metastatic involvement limited to a single N1 station, whereas 19 (20.2%) had multistation N1 disease. Multistation N1 was associated with poorer 5-year DFS (17.8% vs. 52.3%) and OS (27.9% vs. 59.7%). In the adjusted analysis, involvement of multiple N1 stations remained an independent adverse factor for DFS (hazard ratio [HR]: 2.84; 95% confidence interval [CI]: 1.53-5.26; p=0.001) and OS (HR: 2.41; 95% CI: 1.23-4.74; p=0.011), after accounting for pathological stage and pleural invasion. Increasing pathological stage was also associated with worse DFS (HR: 2.49, 95% CI: 1.55-4.01, p<0.001) and OS (HR: 2.36, 95% CI: 1.46-3.81, p<0.001). Conclusion: In clinically occult pN1 NSCLC, multistation N1 involvement and higher pathological stage were independently associated with worse DFS and OS. Detailed pathological assessment of N1 nodal burden may improve postoperative risk stratification.