Colorectal neuroendocrine tumors are a rare malignancy, yet their incidence appears to be increasing. The optimal treatment for the high-grade subset of these tumors remains unclear. We aimed to examine the relationship between different treatment modalities and outcomes for patients with high-grade neuroendocrine carcinomas (HGNECs) of the colon and rectum.

The National Cancer Database (2004-2015) was used to identify patients diagnosed with colorectal HGNECs. The primary outcome was overall survival. A Cox Proportional hazard model was used to identify risk factors for survival.

Overall, 1208 patients had HGNECs; 452 (37.4%) patients had primary tumors of the rectum, and 756 (62.5%) patients had primary tumors of the colon. A total of 564 (46.7%) patients presented with stage IV disease. The median survival was 9.0 months [95% confidence interval (CI) 8.2-9.8]. In multivariable analysis, surgical resection [hazard ratio (HR) 0.54, 95% CI 0.44-0.66; p < 0.001], chemotherapy (HR 0.74, 95% CI 0.69-0.79; p < 0.001), and rectum as the primary site of tumor (HR 0.62, 95% CI 0.51-0.76; p < 0.001) were associated with better overall survival, while older age (HR 1.01, 95% CI 1.00-1.01; p = 0.02) and the presence of metastatic disease (HR 3.34, 95% CI 2.69-4.15; p < 0.001) were associated with worse survival.

Patients with colorectal HGNECs selected for chemotherapy and surgical resection of the primary tumor demonstrated better overall survival than those managed without resection. Patients who were able to undergo systemic chemotherapy may benefit from potentially curative resection of the primary tumor.