Risk stratification for lymph node metastasis using Epstein-Barr virus status in submucosal invasive (pT1) gastric cancer without lymphovascular invasion: a multicenter observational study.

Background: Lymphovascular invasion (LVI) is a strong predictive factor for lymph node metastasis (LNM) in early gastric cancer (GC). This study investigated the risk for LNM in pT1b GC without LVI based on Epstein-Barr virus (EBV) status in addition to conventional clinicopathological parameters.

Methods: In total, 847 consecutive patients of pT1b GC without LVI who underwent surgery at three high-volume centers between 2005 and 2014 were retrospectively analyzed. Clinicopathological parameters and EBV status were evaluated, and univariate and multivariate analyses were performed to estimate LNM risk. With regard to the presence of those three parameters, risk stratification for LNM was performed and compared with a previously proposed risk classification that included low-risk (LNM < 3.0%), intermediate-risk (LNM ≥ 3.0 and < 19.6%), and high-risk (LNM ≥ 19.6%) groups.

Results: EBV-positive GC (EBVGC) accounted for 11.3% (96 of 847) of cases; LNM was lower in EBVGC than in non-EBVGC (1 of 96, 1.0% vs. 71/751, 9.5%). In the multivariate analysis, non-EBVGC [odds ratio (OR) 10.8, 95% confidence interval (CI) 1.48-78.9], age < 65 years (OR 2.13, 95% CI 1.30-3.48), and tumor diameter > 3 cm (OR 2.26, 95% CI 1.36-3.74) were independent risk factors for LNM. Patients with EBVGC were at low risk for LNM whereas those with all of three independent risk factors were at high risk (36 of 168, 21.4%, 95% CI 15.5-28.4).

Conclusion: LNM risk stratification that includes EBV status is useful for clinical decision-making in pT1b GC cases without LVI.