Identification and Validation of Lymphovascular Invasion as a Prognostic and Staging Factor in Node-Negative Esophageal Squamous Cell Carcinoma.

INTRODUCTION Lymphovascular invasion (LVI) is a histopathological feature that is associated with an increased risk for micrometastasis. The aim of this study was to determine the prognostic and staging value of LVI among patients with esophageal squamous cell carcinoma (ESCC) undergoing esophagectomy. METHODS A prospective database of patients with ESCC was used to retrospectively analyze 666 cases to identify the relationship between LVI and survival, and to evaluate predictive accuracy of prognosis after combining LVI and the tumor, node, and metastasis (TNM) system. Pathological slides were reassessed by gastrointestinal pathologists according to the strict criteria; 1000-bootstrap resampling was used for internal validation, and 222 cases from an independent multicenter database were used for external validation. RESULTS LVI was present in 33.8% of patients, and the proportion increased with advancing T and N classification. LVI was an independent predictor of unfavorable disease-specific survival (DSS) (hazard ratio = 1.59, 95% confidence interval: 1.30-1.94) and disease-free survival (DFS) (hazard ratio = 1.62, 95% confidence interval: 1.32-1.98) after T classification. Among node-negative patients, LVI and T classification were two independent predictors of DSS and DFS (p < 0.001). The risk score model combing LVI and T classification improved the predictive accuracy of the TNM system for DSS and DFS by 3.5% and 4.8%, respectively (p < 0.001). The external validation showed congruent results. The DSS of TxN0MO disease with LVI was similar to the DSS of TxN1M0 (both p > 0.05). In contrast, LVI was not associated with DSS or DFS among node-positive patients. CONCLUSIONS The independent prognostic significance of LVI existed only in node-negative patients with ESCC, and the combination of LVI and the TNM system enhanced the predictive accuracy of prognosis. After confirmation, node-negative patients with LVI might be considered for upstaging in pathological staging.