Nodal Zone Count Versus ypN Stage for Predicting First Distant Metastasis After Neoadjuvant Therapy and Esophagectomy in Esophageal Squamous Cell Carcinoma.

BACKGROUND

After neoadjuvant therapy, nodal zone count summarizes the spatial distribution of residual nodal disease, whereas the postoperative pathological nodal category (ypN) is based on the number of metastatic lymph nodes. We aimed to compare nodal zone count with ypN for 3-year prediction of first distant metastasis.

METHODS

In a retrospective single-center cohort (2015-2023) of 557 patients with esophageal squamous cell carcinoma undergoing neoadjuvant therapy and McKeown esophagectomy with three-field lymph node dissection, we compared Fine-Gray competing risks models differing only in ypN (0-3) versus nodal zone count (0-4, with 4 indicating ≥4); fivefold cross-validation generated out-of-fold 3-year cumulative incidence predictions evaluated by time-dependent area under the curve (AUC) and Brier score with paired bootstrap 95% confidence intervals (CIs). Calibration was assessed and decision curve analysis performed at 3 years.

RESULTS

During median follow-up of 3.52 years, 115 first distant metastasis events occurred. Three-year cumulative incidence increased from 13% (0 zones) to 42.5% (≥3 zones). In multivariable analysis, each additional involved zone was associated with higher risk (subdistribution hazard ratio 1.480, 95% confidence interval [CI] 1.273-1.722). At 3 years, nodal zone count showed slightly higher AUC (difference 0.0165, 95% CI 0.0055-0.0275) and lower Brier score versus ypN. Net benefit was similar overall, modestly favoring nodal zone count at moderate thresholds.

CONCLUSIONS

Nodal zone count showed a clear absolute-risk gradient and modestly better 3-year predictive performance than ypN, with broadly similar net benefit. External validation is needed before clinical implementation or use in surveillance planning.