Nodal Skip Metastasis in Esophageal Squamous Cell Carcinoma Patients Undergoing Three-Field Lymphadenectomy

The clinical and prognostic implications of nodal skip metastasis (NSM) remain unclear in patients with esophageal squamous cell carcinoma (ESCC).

Patients with pathologically confirmed node metastasis who underwent three-field lymphadenectomy from January 1999 to December 2008 were retrospectively enrolled. The node station is determined based on the classification of the Japanese Society for Esophageal Diseases. NSM is defined as the occurrence of metastases in nodes distant from the primary tumor (station 2 or 3) without the involvement of the adjacent nodes (station 1). To balance the baseline characteristics, a matched cohort was generated by propensity score matching analysis with covariates of age, sex, pathologic status, and treatment. The prognostic implication of NSM was assessed using log-rank tests and Cox regression analyses.

In the entire cohort, the NSM rate was 64.0% (657 of 1026); NSM was substantially associated with clinicopathologic variables, including an increased likelihood of middle thoracic tumor location and limited nodal status. Univariate analysis showed similar outcomes between patients with and without NSM (unadjusted hazard ratio [HR] 1.018, 95% confidence interval [CI]: 0.855 to 1.213, p = 0.838). A similar result was obtained in the matched cohort (unadjusted HR 1.057, 95% CI: 0.870 to 1.285, p = 0.578). Although in patients with solitary node metastasis, patients with NSM presented a worse prognosis than patients without (p = 0.043 in log-rank test).

NSM is a common phenomenon in ESCC. Among ESCC patients who underwent three-field lymphadenectomy, NSM is associated with a relatively poor prognosis in individuals with solitary node metastasis.