Effects of Lymphatic and Venous Invasion Status on Postoperative Prognosis and Metastasis Pattern in Patients With Esophageal Squamous Cell Carcinoma: A Retrospective Cohort Study.

Abstract

Background: Lymphovascular invasion (LVI) is a recognized predictor of poor postoperative outcomes in patients with esophageal squamous cell carcinoma (ESCC). However, only a few studies have evaluated lymphatic invasion (LI) and venous invasion (VI) separately across contemporary perioperative strategies. This study was conducted to evaluate the clinicopathological associations, survival outcomes, and recurrence patterns of LI and VI in patients with ESCC who underwent upfront surgery or neoadjuvant therapy followed by esophagectomy.

Methods: We retrospectively analyzed 446 consecutive patients who underwent esophagectomy between January 2003 and March 2022. The patients were categorized into four pathological groups based on their LI and LV status: LI(-)/VI(-), LI(+)/VI(-), LI(-)/VI(+), and LI(+)/VI(+). Overall survival (OS), recurrence-free survival (RFS), and recurrence patterns were evaluated according to LI and VI status in patients who underwent upfront surgery, neoadjuvant chemotherapy (NAC), or neoadjuvant chemoradiotherapy (NACRT) followed by esophagectomy.

Results: Of the 446 patients, 121, 197, and 128 underwent NAC, NACRT, and upfront surgery, respectively. Patients in the LI(+)/VI(+) group had the poorest OS and RFS among all the LI/VI groups. Multivariable analysis showed that isolated LI positivity was associated with inferior RFS compared with LI(-)/VI(-) (hazard ratio [HR] 1.55; p = 0.04). Unadjusted Kaplan-Meier comparisons showed no significant difference between isolated LI positivity and isolated VI positivity. Regarding distant metastasis, multiorgan metastasis occurred more frequently in the LI(+)/VI(+) group than in the other LI/VI groups.

Conclusions: LI and VI provide distinct and complementary prognostic information for patients with ESCC. VI positivity, especially when it coexists with LI, is associated with worse postoperative survival and a higher risk of distant metastasis. These findings support the use of risk-adapted postoperative strategies for improved clinical outcomes.