Spatial metrics of lymph node metastasis refine prognostic stratification of T1-T2 esophageal squamous cell carcinoma.

Abstract

To determine whether the spatial extent of lymph node metastases (LNM) predicts survival in early esophageal squamous cell carcinoma (ESCC). A retrospective cohort of 185 patients with T1-T2 ESCC and pathologically confirmed LNM who underwent radical esophagectomy were enrolled in this study. We defined maximal LNM distance as the linear distance from the tumor to the farthest metastatic lymph node and cross-zonal dissemination (Δ) as the number of anatomical zonal boundaries between the tumor and the farthest node. Survival outcomes were assessed by Kaplan-Meier and multivariable Cox regression. X-tile analysis identified 45 mm as the optimal cutoff for LNM distance, above which overall survival was significantly reduced (log-rank P < .001). On multivariable analysis, both N2 stage (hazard ratios [HR], 5.13; 95% confidence interval [CI], 1.47-17.91; P = .010) and LNM distance >45 mm (HR, 2.06; 95% CI, 1.07-3.96; P = .030) were independent predictors of mortality. Cross-zonal dissemination was observed in 51.9% of patients. Moreover, patients with Δ1+Δ2 involvement exhibited significantly worse overall and disease-free survival compared with those with Δ0 (overall survival P = .004; disease-free survival P = .034). Multivariable analysis confirmed Δ1+Δ2 as an independent prognostic factor (HR, 1.93; 95% CI, 1.01-3.67; P = .045). In T1-T2 ESCC, both metastatic distance and cross-zonal dissemination provide independent prognostic information beyond simple lymph node counts. Therefore, incorporating spatial metrics into staging may improve risk stratification and guide treatment decisions.