The effect of primary site, functional status and treatment modality on survival in gastroenteropancreatic neuroendocrine neoplasms with synchronous liver metastasis: a US population-based study

BACKGROUND: The incidence of indolent gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has increased dramatically. GEP-NENs often present late with concomitant liver metastasis, which is associated with poorer outcomes. METHODS: This is a retrospective cohort study of 3,188 patients with liver metastatic GEP-NENs from the national scale Surveillance, Epidemiology, and End Results (SEER) database in the USA between 2010 and 2016. The population-based sample of GEP-NENs with liver metastasis was stratified by primary site (intestinal, pancreatic or gastric), surgical intervention and functional status. RESULTS: Of the 3,188 patients with liver metastatic GEP-NENs in this study, intestinal NENs (iNENs) were the most common and displayed the best 5-year survival of 42.6% compared to 25.8% in pancreatic NENs (pNENs) and 12.0% in gastric NENs (gNENs). Surgical intervention [hazard ratio (HR): 0.46, 95% CI: (0.40–0.53), P<0.001] and carcinoid subtype showed robust survival advantages across all groups. pNENs with liver metastasis were associated with the greatest benefit of surgery [HR: 0.55, 95% CI: (0.41–0.75), P<0.001] while iNENs were the most commonly treated by surgery. After risk adjustment, primary site was not associated with outcome in the non-surgical group. CONCLUSIONS: Taken collectively, when diagnosed with liver metastasis, iNENs conferred a better overall prognosis than both pNENs and gNENs. Primary surgical resection, especially of carcinoid type tumors, emerged as a robust prognostic indicator of better outcomes irrespective of primary site. This finding was most pronounced in liver metastatic pNENs. When possible, we recommend surgical intervention in GEP-NENs with liver metastasis.