Pattern and risk factors for distant metastases in gastrointestinal neuroendocrine neoplasms: a population-based study

An increased incidence of gastrointestinal neuroendocrine neoplasms (GI-NENs) has been reported worldwide, and metastasis is the leading cause of GI-NEN-related death. Studies of different metastatic patterns in patients with different primary sites are limited. A population-based retrospective cohort study was conducted with the Surveillance, Epidemiology, and End Results (SEER) database. Patients with a GI-NEN diagnosis between 2010 and 2014 were included. All statistical analyses were performed using Intercooled Stata 12.0 software. There were 12,501 patients eligible for analysis. The metastatic status, primary sites, and histology types affected the patients' overall survival. The liver was the most common metastasis site (65.21% of patients with metastases). Esophageal NENs had the highest risk of metastasis (49.35%), whereas appendiceal NENs had the lowest risk of metastasis (2.79%). Neuroendocrine carcinomas (NECs) were more likely to develop metastatic disease than were neuroendocrine tumors (NETs); 7.12% of patients with NET and 30.20% of patients with NEC developed metastatic disease. The metastatic patterns varied according to the different primary sites and histology types. NECs had a higher potential to develop extrahepatic metastasis at all primary sites than did NETs. Regarding the choice of treatment, surgical resection of primary lesions lowered the risk of tumor-specific death (HR = 0.37, CI: 0.30-0.46, P < 0.01), but surgical resection of metastatic sites did not confer an extra survival benefit (HR = 0.82, CI: 0.63-1.06, P = 0.14). Different primary sites and histology types of GI-NENs have different metastatic patterns and survival. This knowledge could help clinicians to identify patients who require extra surveillance, provide insight for future studies on the mechanisms of metastasis, and establish a prognostic prediction model.