Prognostic impact of extracapsular extension of lymph nodes in resected lung cancer: analysis by new N subcategories and histologic types.

Abstract

Objectives: Despite being an R1 descriptor, the effects of extracapsular extension (ECE) on survival are inconsistent and remains invalidated under N2 subcategorization (pN2a and pN2b). This study aimed to validate the survival effect of ECE across N subcategories and histologic types.

Materials and methods: Patients who underwent lobectomy or pneumonectomy for NSCLC between 2010 and 2022, with proven pN-positive status and Union for International Cancer Control R0 designation, were retrospectively included. Effect of ECE on overall survival (OS) and recurrence-free survival (RFS) was assessed using multivariable Cox proportional hazard models, while that on recurrence patterns (locoregional vs. distant) was assessed using Fine-Gray subdistribution hazard models.

Results: Among 1713 patients included, the prevalence of ECE increased with the pN category: 11.6 % in pN1 (87/751), 17.6 % in pN2a (104/581), and 44.6 % in pN2b (170/381). ECE was an independent risk factor for poor OS and RFS in all pN-positive patients, after covariate adjustment (all p < 0.05). Patients with ECE consistently exhibited higher risks of mortality and RFS events compared to their ECE-negative counterparts across pN1, pN2a, and pN2b (all p < 0.05). Upon stratification by histologic type, ECE exhibited negative effects exclusively in adenocarcinoma (all p < 0.05), not in non-adenocarcinoma (all p > 0.05). ECE was an independent risk factor for locoregional recurrence (p = 0.002) but not for distant recurrence (p = 0.090).

Conclusion: ECE demonstrated a negative effect across pN1, pN2a, and pN2b, validating its role as an R1 descriptor. The negative effect of ECE exclusively in adenocarcinoma highlights the need to interpret ECE status with respect to histology.