C. Mosquera1, N. J. Koutlas1, N. A. Vohra1, T. L. Fitzgerald1 1East Carolina University Brody School Of Medicine,Surgical Oncology,Greenville, NC, USA
Introduction: Because of limited sample size in existing case series, the natural history and optimal management for patients with high-grade gastroenteropancreatic neuroendocrine tumors (GEP-NET) is poorly understood. In order to better grasp the implications of this diagnosis, a large cohort study was undertaken.
Methods: Patients diagnosed with high-grade GEP-NET from 1988-2010 were identified in the SEER registry. Primary sites with 5 or fewer patients, unknown surgery, or stage IV (n=171) were excluded.
Results:A total of 335 patients met inclusion criteria. Median age was 65 years, a majority were female (52.2%), white (84.5%), and had surgery (89.0%). The most common primary site was colorectal (38.2%) followed by appendix (19.7%), small bowel (15.8%), pancreas (14.9%), and gastric (11.3%). Median tumor size was 3.5 cm. The most frequent T classification was T3 (33.7%) followed by T4 (21.5%), T1 (16.4%), and T2 (9.0%). Surgical resection was performed in 89% of patients and varied by site, more commonly for appendix (97.0%), colorectal (94.5%), and small bowel (88.7%) and less commonly for pancreatic (78.0%) and gastric (71.1%) (p< 0.0001) primaries. Nodal involvement was frequent (41.2%) and varied by site; pancreas (57.8%), colorectal (55.1%), small bowel (44.0%), appendix (27.4%), and gastric (24.2%) (p= 0.0002). Pancreatic (57.5%) and colorectal (52.4%) neoplasms were more likely to be > 4 cm in size (p< 0.0001). The 5-year disease-specific survival (5-y DSS) was 63.3%, longest for small bowel (81.1%), followed by gastric (76.9%), appendix (75.5%), colorectal (54.2%), and pancreas (45.4%) (p= 0.0003). 5-y DSS was also associated with age (< 65 years 70.7% vs. ≥ 65 years 56.1%; p= 0.0034), node status (N0 73.6% vs. N1 54.2%; p= 0.0012) and surgery (Yes 64.6% vs. No 51.5%; p= 0.058). On multivariate analysis, node status (OR 1.91; p= 0.0091), surgery (5.25; p= 0.0010), and primary site continued to be associated with survival while age was not (1.50; p= 0.089). More specifically, small bowel (5.41; p= 0.0003) and gastric (3.90; p=0.0075) primaries had better survival compared to appendix (1.89; p= 0.16), colorectal (1.16; p= 0.79), and pancreas (referent). The incidence of high-grade GEP-NET increased from 0.03 to 0.19 per 100,000 over the study period, (R2= 0.79, p< 0.0001).
Conclusion: High-grade GEP-NET is a rare neoplasm that is increasing in incidence. Primary site and nodal status are useful predictors of survival. In contrast to current literature for this disease, a benefit was demonstrated for patients with localized disease undergoing surgical resection.