Overall survival (OS) in gastrointestinal (GI) neuroendocrine tumors (NETs) based on primary site, stage, and surgery.

643 Background: There are limited data on the impact of primary site and surgical intervention on long-term outcomes in GI-NETs. We hypothesized that primary site would be associated with differences in stage-specific OS. Methods: In the National Cancer DataBase, using histology codes, we identified 124,081 GI-NETs diagnosed between 2004-2019 in individuals 18 years or older. OS was estimated by the Kaplan-Meier method. Differences in survival based on primary site, stage, and surgical intervention were assessed using a Cox proportional hazards model, accounting for multiple comorbidities, e.g. Charlson-Deyo Comorbidity Index. Results: The most common primary site for GI-NETs was small intestine (33.6%), followed by colon, rectum, pancreas, and stomach comprising 19.8%, 17.5%, 15.5%, and 9.2%, respectively. Patients with stage I-III NETs undergoing surgery had significantly better median OS compared to those without surgery (mOS 197 vs 115 mo., p<0.0001 by log rank test). Patients with stage IV NETs undergoing primary resection also had improved mOS vs those with no surgery (125 vs 54 mo., p<0.0001). For stage I-III patients without surgery, 2-yr and 5-yr survival rates were highest in the rectum and lowest in small intestine ( p<0.0001). Among those with stage I-III with surgery, 2-yr and 5-yr survival rates were also highest in the rectum, and lowest in the biliary system at 89% and 82% ( p<0.0001). In contrast, for stage IV patients without primary resection, 2-yr and 5-yr survival rates were highest among small intestine and lowest in the rectum ( p<0.0001). Among those who had primary tumor resection, 2-yr and 5-yr survival rates were highest in pancreas and lowest in colon at 2 yrs and rectum at 5 yrs ( p<0.0001). Conclusions: Surgical intervention for GI-NETs is associated with improved OS in both localized and stage IV disease, with consistent trends across different primary sites. Primary tumor resection was associated with the largest increase in 5-yr survival for stage IV NETs arising from pancreas and stomach. Patient selection for surgery undoubtedly contributed to the improved OS, but resection of primary tumors in stage IV GI-NETs may have a disease modifying effect. Further study is warranted with more granular data to identify patients with stage IV GI-NETs who may benefit from primary tumor resection.[Table: see text]