Combined quantitative-anatomical assessment of metastatic lymph nodes refines prognostic stratification in resected gastric cancer

Lymph node (LN) status is a cornerstone of gastric cancer (GC) staging. Current AJCC/UICC TNM nodal categories are primarily numerical, but whether integrating anatomical distribution with quantitative nodal burden provides additional prognostic information remains uncertain, particularly in Western cohorts.

We retrospectively analyzed 249 patients who underwent upfront curative-intent surgery for GC at a single tertiary center in Spain (2001-2019). Metastatic LNs were classified as perigastric (stations 1-6) or extraperigastric (stations 7-12). Disease-free survival (DFS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier analysis and Cox regression. Interaction between LN location and nodal burden (lymph node ratio, LNR) was evaluated, and a combined quantitative-anatomical nodal classification was explored.

LN metastases were present in 56.6% of patients; 38.3% of node-positive patients had extraperigastric metastases. In N+ patients, extraperigastric involvement was associated with worse DFS and CSS and remained independently prognostic in multivariable models. LN location showed a significant interaction with LNR for CSS (Loc×LNR HR 2.64; p < 0.001), indicating increasing adverse impact of extraperigastric metastases with higher nodal burden. The prognostic value of LN location was most evident in pN3 disease (n = 51), where it was the only independent factor for DFS (HR 3.166) and CSS (HR 3.240). A combined LNR-location classification further stratified prognosis and identified a high-risk subgroup (LNR>25% with extraperigastric metastases).

Metastatic LN location provides prognostic information beyond numerical staging, particularly in advanced nodal disease. Integrating quantitative and anatomical nodal assessment may refine prognostic stratification and identify patients with high-risk disease.