Background: Little is known about the specific risks of metastasis in esophageal adenocarcinoma in relation to invasion depth or other pathologic factors. Methods: We conducted a multicenter retrospective study in 13 high-volume centers in Japan from January 2000 to October 2014 to elucidate the risk of metastasis of esophageal adenocarcinoma. A total of 458 patients (217 surgically resected and 241 endoscopically resected) with esophageal adenocarcinoma or esophagogastric adenocarcinoma involving the esophagus were included. Metastasis was considered positive if there was histologically confirmed metastasis in the surgical specimen or clinically confirmed metastasis during follow-up. Metastasis was considered negative if no metastasis was identified in resected specimens and during follow-up in patients treated surgically or no metastasis during follow-up for >5 years in patients treated by endoscopic resection. Results: Metastasis was identified in 72 patients. Multivariate analysis confirmed lymphovascular involvement [odds ratio (OR) 6.20; 95 % confidence interval (CI) 3.12–12.32; p < 0.001], a poorly differentiated component (OR 3.69; 95 % CI 1.92–7.10; p < 0.001), and lesion size >30 mm (OR 3.12; 95 % CI 1.63–5.97; p = 0.001) as independent risk factors for metastasis. No metastasis was detected in patients with mucosal cancer without lymphovascular involvement and a poorly differentiated component (0/186 lesions) or in patients with cancer invading the submucosa (1–500 µm) without lymphovascular involvement, a poorly differentiated component, and ≤30 mm (0/32 lesions). Conclusions: Mucosal and submucosal cancers (1–500 µm invasion) without risk factors have a low incidence of metastasis and may thus be good candidates for endoscopic resection.
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