BACKGROUND: Neuroendocrine tumors (NETs) of the esophagus and stomach are rare neoplasms with variable behavior. We aim to describe their epidemiology and response to treatment.

METHODS: NETs of the stomach and the esophagus were selected from the National Cancer Database (2004-2013) and classified by location. Survival analyses were performed with respect to tumor characteristics and treatment variables.

RESULTS: NETs of the stomach (n = 2700; 92.8%) and esophagus (n = 210, 7.2%) were identified. Gastric cardia NETs had demographics and behavior similar to esophageal tumors and were associated with worse overall survival than NETs of the noncardia stomach independent of grade (p < 0.001). Poorly differentiated histology [hazard ratio (HR) 4.14, 95% confidence interval (CI) 2.26-7.57; p < 0.001] and distant metastases (HR 3.28, 95% CI 1.94-5.56; p < 0.001) were the greatest independent predictors of survival. For patients with poorly differentiated NETs, surgery was the only treatment to have benefit on overall survival (HR 0.38, 95% CI 0.27-0.54; p < 0.001) regardless of extent of disease. There was no additional benefit to adjuvant chemotherapy or radiation in patients undergoing resection (p = 0.39), even for patients with lymph node metastases (surgery alone versus surgery plus adjuvant therapy, p = 0.46), distant metastases (p = 0.19), or positive margins (p = 0.33).

CONCLUSIONS: Esophageal and gastric cardia NETs have worse survival than those of the noncardia stomach. Surgery offers the only survival benefit for poorly differentiated tumors, with no additional survival advantage to adjuvant chemotherapy or radiation.