Typical carcinoids, goblet cell carcinoids, mixed adenoneuroendocrine carcinomas, neuroendocrine carcinomas and adenocarcinomas of the appendix: a comparative analysis of survival profile and predictors

Background: Goblet cell carcinoids (GCC) and other atypical neuroendocrine tumors (NET) of the appendix as well as appendiceal adenocarcinoma are usually managed with the same algorithm as colon cancers. This study investigates clinicopathological features that are predictive of survival outcomes for appendiceal NET and adenocarcinoma. Survival profiles for the histologic subtypes of appendiceal NET and adenocarcinoma were compared. Methods: A retrospective review of appendiceal NET and adenocarcinoma for patients who are 18 years and above in the SEER database from 2010 to 2014. Results: Females outnumbered males in a 1.3 to 1 ratio in the NET subgroup and 1.1 to 1 ratio in the adenocarcinoma group. The mean age at diagnosis for all NET was 50.3 +/- 17 years while that of adenocarcinomas was 60.8 +/- 14.1 years. Within the NET subgroups, the mean ages for typical carcinoids (TC), GCC, NEC and MANEC were 42.9 +/- 17.3, 56.7 +/- 13.7, 45.6 +/- 17.4 and 59.7 +/- 12.8 years, respectively. Overall survival for adenocarcinoma was 86.3%, 73.5%, 65.7%, and 57.6% for 1-, 2-, 3-and 4-year OS, respectively. For NET, TC showed better survival profile with 1-and 4-year overall survival of 97.4% and 95.7%, respectively while MANEC had the worst survival outcome with 1- and 4-year OS of 88.6% and 62.2%, respectively. GCC had a better 1-year OS compared to NEC (95.5% versus 92.9%) but showed slightly worse 4-year OS (82% versus 84.8%). Age at diagnosis (HR 1.03), African-American race (HR 1.47) and stage IV disease (HR 9.58) were independent predictors of survival for appendiceal adenocarcinoma. For NET, advanced age at diagnosis, advanced disease stage and the African-American race were identified as negative independent predictors of survival. Conclusions: While prior studies have suggested that atypical NET (GCC, NEC and MANEC) are more likely to present at more advanced stages, this study showed that most cases of GCC, MANEC and NEC were diagnosed at stages I and II. Appendiceal adenocarcinoma, on the other hand, presented mostly at stage IV. With respect to OS, atypical histologic subtypes of NET have worse outcome compared to TC. Although better OS was noted for GCC, NEC and MANEC when compared to adenocarcinoma, this benefit was lost in stage IV disease where adenocarcinoma recorded better 1-and 4-year OS. Prospective and randomized studies which provide granular details of treatment are needed to better define treatment algorithm for appendiceal NET.