Individual risk calculator to predict lymph node metastases in patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study

<b>Background and study aims:</b> There is a risk for lymph node metastases (LNM) after endoscopic resection of early esophageal adenocarcinoma (EAC). The aim of this study was to develop and internally validate a prediction model that estimates the individual metastases risk in patients with pT1b EAC. <b>Patients and methods:</b> This is a nationwide, retrospective, multicenter cohort study. Patients with pT1b EAC and treated with endoscopic resection and/or surgery between 1989 and 2016 were included. Primary endpoint was the presence of LNM in surgical resection specimen or the detection of metastases during follow-up. All resection specimens were histologically reassessed by specialized gastrointestinal pathologists. Subdistribution hazard regression analysis was used to develop a prediction model. The discriminative ability of this model was assessed using the c-statistic. <b>Results:</b> 248 patients with pT1b EAC were included. Metastases were seen in 78 patients, and the 5-year cumulative incidence was 30.9% (95% CI 25.1%-36.8%). The risk for metastases increased with submucosal invasion depth (subdistribution hazard ratio [SHR] 1.08, 95% CI 1.02-1.14, for every increase of 500 μm), for tumors with lymphovascular invasion (SHR 2.95, 95% CI 1.95-4.45) and for larger tumors (SHR 1.23, 95% CI 1.10-1.37, for every increase of 10 mm). The model demonstrated a good discriminative ability (c-statistic 0.81, 95% CI 0.75-0.86). <b>Conclusions:</b> One third of patients with pT1b EAC experienced metastases within 5 years. The probability for developing post resection metastases can be estimated with a personalized predicted risk score incorporating tumor invasion depth, tumor size and lymphovascular invasion. This model needs to be externally validated before implementation into clinical practice.