Clinical Implications of Metastatic Nodal Burden: Stratifying Risk in Resected N1 and N2 NSCLC

Current anatomical N staging often fails to reflect prognostic heterogeneity within N1 and N2 non-small cell lung cancer (NSCLC). We evaluated whether metastatic nodal burden, defined as the tumor deposit size, provides additional prognostic information beyond conventional staging.

We retrospectively analyzed 1495 patients with pN1 (n = 633) or pN2 (n = 862) NSCLC who underwent curative surgical resection between 2010 and 2019. Metastatic tumor deposit size was categorized as ≤ 5 mm, 5-9 mm, and ≥ 10 mm. Linearity between tumor size and overall survival (OS) or recurrence-free survival (RFS) was assessed using restricted cubic splines. Kaplan-Meier and multivariable Cox regression analyses were performed.

Median metastatic deposit size was 5 mm (interquartile range [IQR] 3-9) in pN1 and 10 mm (IQR 5.1-16) in pN2. In pN1, high-burden patients (≥ 10 mm) had significantly worse 5-year outcomes than low-burden group (OS: 60.0% versus 75.5%, hazard ratio [HR] 1.66; RFS: 42.2% versus 50.9%, HR 1.83). In pN2, burden independently predicted RFS (5-year rate: 26.2% for ≥ 10 mm versus 42.4% for < 5 mm; HR 1.72, p < 0.001). Notably, radiologically occult low-burden metastasis (< 5 mm) was prevalent (41% in pN1, 19% in pN2) and associated with favorable survival, yet frequently undetectable on standard preoperative imaging.

Metastatic nodal burden reflects meaningful prognostic variation within pN1 and pN2 disease. These findings suggest that considering metastatic burden may help refine postoperative risk assessment and support more individualized management in surgically treated NSCLC.