Prognostic comparison of lymph node metastasis subtypes in lung adenocarcinoma: clinical implications of intranodal
Jia-Yong Wu1, Guo-Zhong Liang1, Tian-Qing Chen1
1Xiaolan Clinical Institute of Shantou University Medical College, No. 65 Jucheng Rd., Xiaolan Dist., Zhongshan 528415 Guangdong Province, PR China; Department of Cardiothoracic Surgery, Xiaolan People's Hospital of Zhongshan (The Fifth People's Hospital of Zhongshan), No. 65 Jucheng Rd., Xiaolan Dist., Zhongshan 528415 Guangdong Province, PR China.
Background:
Lung adenocarcinoma (LUAD) prognosis is strongly influenced by lymph node (LN) status. While extranodal extension (ENE) is a recognized negative prognostic factor, the International Association for the Study of Lung Cancer (IASLC) has proposed reclassifying ENE from R0 (complete resection) to R1 (incomplete resection). The prognostic significance of intranodal metastasis (INM) remains less defined. This study aims to compare the prognosis of LUAD patients with INM versus ENE to inform potential refinements to the R classification system.
Methods:
This retrospective study enrolled 357 patients with pT1-3N0-1M0 LUAD who underwent lobectomy with systematic lymph node dissection between 2015 and 2021. Patients were stratified into three groups based on postoperative pathology: no LN metastasis (N0, n = 180), INM (n = 124), and ENE (n = 53). Overall survival (OS) and disease-free survival (DFS) were compared using Kaplan-Meier and Cox regression analyses.
Results:
Among 177N1-stage patients, no significant difference in OS or DFS was observed between the INM and ENE groups (p > 0.05). However, both the INM and ENE groups showed significantly worse OS and DFS compared to the N0 group (p < 0.05). Multivariate analysis confirmed LN metastasis as an independent adverse prognostic factor for both DFS (HR = 2.95, 95 % CI: 1.32-6.61, P = 0.008) and OS (HR = 3.11, 95 % CI: 1.52-6.38, P = 0.002). Patients with nodal metastasis also had a significantly higher risk of recurrence.
Conclusion:
In N1-stage LUAD, the prognosis of patients with INM is comparable to that of patients with ENE, with both groups exhibiting significantly poorer outcomes than node-negative patients. These findings suggest that the presence of nodal metastasis, regardless of extracapsular extension, may represent occult residual disease. We propose that INM, alongside ENE, should be considered for classification as incomplete resection (R1) to better guide adjuvant therapy strategies.
