Lymph Node Pathologic Grading Strategy: under the backdrop of the IASLC Grading System for Invasive Lung Adenocarcinoma - a retrospective cohort study among Asian patients.

BACKGROUND: IASLC grading system has demonstrated the prognostic value of pathologic patterns in primary tumors, establishing a benchmark for survival outcomes. However, whether there is a potential grading system for metastatic lymph nodes (mLNs) to predict the outcome remains unknown. METHODS: From 2011 to 2021, a large cohort of 3150 patients with invasive lung adenocarcinoma (LUAD) was retrospectively analyzed and classified according to their N stages. Patients were further stratified according to different pathologic grades for each mLN as well as the quantity of mLNs, which we named mLN GRADE. Survival analysis was performed to reveal the association between mLN GRADE and long-term outcomes. RESULTS: The prognostic differences between N categories were highly significant in terms of both overall survival (OS) and recurrence-free survival (RFS) (n = 3150). High mLN GRADE was robustly correlated with higher pathologic grade (p < 0.001) in primary tumors, higher p-TNM stage (p = 0.008), and worse RFS in patients with different N stages. High mLN GRADE was linked to higher EGFR mutation (p = 0.021) in N1 patients, but not in N2 patients. When patients were further stratified by N stage, multivariate analysis identified high mLN GRADE as an independent prognostic factor for worse RFS in both N1 and N2 subgroups. CONCLUSIONS: High mLN GRADE is significantly associated with worse RFS in patients with different N stages. mLN GRADE may help supplement the current N descriptor.