Background: Neuroendocrine tumors (NETs) are comprised of a group of biologically and clinically heterogenous malignancies arising from a variety of anatomic sites, the majority of which lie within the gastrointestinal tract. Prior literature has reported on the association between NETs and other primary malignancies (OPM), most of which also end up being within the gastrointestinal tract, but these studies are limited by small sample sizes. We aim to further analyze the association of NETs and OPM on a larger scale using a population-based cancer registry. Methods: Malignant primary cancer with NET features were identified from the Surveillance Epidemiology and Ends Results (SEER) registry between 1975 and 2017. The histology/behavior of NET included carcinoid tumor, neuroendocrine carcinoma, pancreatic endocrine tumor, atypical carcinoid tumor, and other including insulinoma, glucagonoma, gastrinoma, VIPoma, somatostatinoma and enterochromaffin cell carcinoid. First NET observation from each patient was examined. Patients with NET were grouped into three categories: only one primary cancer with NET, first primary cancer with NET and first primary cancer without NET based on sequence number of primary cancer recorded in SEER. Distribution of NET between gastrointestinal (GI) and non-GI sites was described. Demographics were compared by NET sequence group and between GI and non-GI sites. Results: 45,896 patients with NET were analyzed (77.9% Caucasian, 47.0% male, median age 62.0 years). More than half (65.7%) of the NETs were observed in GI sites. Within the GI tract, 31.3% were in the small intestine, 25.1% in the rectum, 16.6% in pancreatobiliary, and < 11% in other GI locations. Age at NET diagnosis was younger in those with GI NETs (median 60.0 vs 65.0, p < 0.001 ). 71.2% of NET found in only cancer diagnosis, 10.4% of NET in first followed by a second primary malignancy, and 18.4% in a non-NET primary followed by NET. Mean age was 58.9 for NET primary only, 61.0 for NET primary first and 68.3 for non-NET primary first (p < 0.0001). More Caucasian patients had non-NET primary first (82.3%) compared to NET primary only (76.9%) and NET primary first (75.5%). No gender differences were observed amongst the three groups. Carcinoid tumor histology was more prevalent in NET primary first (78.6%) compared to NET primary only (67.3%) and non-NET primary first (66.6%), while neuroendocrine carcinoma histology was more prevalent in NET only (27.4%) and non-NET first (29.3%) compared to NET first. Conclusions: 28.8% of patients with NETs were found to have OPM, either preceding or following their NET diagnosis. It is imperative that patients with NET undergo age-appropriate cancer screening to help identify any concurrent malignancies. Further research is warranted to identify the location of such additional malignancies and the timeframe in which they occur in relation to the NET.

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