R. L. Guyton Jr1, M. W. McMullen2, C. S. Lea2, J. Brinkley2,3, C. Mosquera1, T. L. Fitzgerald1 1East Carolina University Brody School Of Medicine,Division Of Surgical Oncology,Greenville, NC, USA 2East Carolina University Brody School Of Medicine,Department Of Public Health,Greenville, NC, USA 3American Institutes For Research,Chapel Hill, NC, USA
Introduction: The incidence of high-grade gastroenteropancreatic neuroendocrine tumors (HG GEP-NET) is increasing, but a lack of consensus remains regarding optimal treatment regimens. This study examines whether surgical resection and adjuvant chemotherapy provide a survival advantage for patients with HG GEP-NET.
Methods: Incident cases of HG GEP-NET from 2004-2013 were obtained from the National Cancer Data Base. Data examined included clinical and pathologic characteristics at diagnosis, treatment strategies, and survival outcomes. Univariate and Cox regression analyses were performed to examine survival outcomes.
Results: In total, 4,630 HG GEP-NET patients were identified. The median age of diagnosis was 66 years. A majority of patients were male (55%), white (84%), and had a colorectal primary (41%). Surgical resection was associated (p < .0001) with survival on univariate analysis. On Cox regression analysis, surgical resection remained a significant predictor of survival (HR = 0.43, 95% CI 0.37–0.49) after adjusting for age, primary site, tumor size, and regional lymph node (RLN) involvement. A total of 1,903 HG GEP-NET underwent surgical resection of the primary site. On Cox regression analysis, primary site (colorectal, referent; appendix, HR = 0.51, 95% CI 0.36–0.71; small intestine, HR = 0.63, 95% CI 0.50–0.77; pancreas, HR = 0.80, 95% CI 0.66–0.96) were associated with improved survival after adjusting for age, tumor size, and RLN involvement, however, adjuvant chemotherapy (HR = 0.90, 95% CI 0.79–1.02) was not. Multiple models were constructed to define the benefit of chemotherapy based on the primary site: Model 1 – colorectal primaries; Model 2, primaries of the ampulla of Vater, esophagus, hepatobiliary, and stomach; and Model 3 – primaries of the appendix, pancreas, and small intestine. On Cox regression analysis, adjuvant chemotherapy conferred a survival benefit in Model 1 (HR = 0.68, 95% CI 0.58 – 0.81), indicated no significant difference in survival in Model 2 (HR = 0.90, 95% CI 0.68 – 1.20), and a survival detriment in Model 3 (HR = 1.66, 95% CI 1.30 – 2.13).
Conclusion: Surgical resection was associated with a survival advantage over all primary sites for HG GEP-NETs. Adjuvant chemotherapy may be beneficial for colorectal HG GEP-NET compared to surgery alone; however, the role of adjuvant chemotherapy for other primary sites is unclear.
