An Analysis of Clinical Features With 18 Biliary Neuroendocrine Tumor Cases

Abstract

Background: Small intestinal carcinoids (SIC) are the most common small bowel malignancies. No population-based study has examined the risk for, and prognosis of, metachronous cancers and SICs. Aims: To determine: 1) the risk of developing SIC before and after other primary malignancies (PM); 2) the prognosis of patients with SIC, with and without another PM. Methods: We used the Surveillance, Epidemiology, and End-Results (SEER) database to identify pts diagnosed with SICs between 1973-2007. Multiple Primary-Standardized Incidence Ratios were calculated as an approximation of relative risk (RR) to explore the association of SICs with metachronous malignancies. Kaplan-Meier (K-M) methods and Cox Proportional-Hazard (CPH) models were used to test survival differences among SIC patients with and without another PM. Multivariate logistic regression was used to predict the factors associated with risk of a future (non-SIC) malignancy. Results: We identified 8,331 patients with SICs. Of these, 2,424 (29%) had an additional PM at some time. The most common sites were prostate (26.2%), breast (14.3%), colon (9.1%), lung/bronchus (6.3%), and bladder (5.3%). 67% had a PM diagnosed before the SIC (pre-SIC), 33% after (post-SIC); 8% had a PM both before and after SIC. Among the pre-SIC group, the risk of future SIC was increased after cancers of the small bowel (RR 11.86 [95%CI 6.13-20.72]), esophagus (RR 4.05 [1.10-10.36]), colon (RR 1.39 [1.05-1.81]), kidney (RR 1.93 [1.12-3.09]), prostate (RR 1.38 [1.17-1.62]), and leukemia (RR 2.15 [CI 1.18-3.61]). Among the post-SIC group, there was an increased risk of future PM of the small bowel (RR 8.78 [4.54-15.34]), liver (RR 2.49 [1.08-4.91]), prostate (RR 1.25 [1.0-1.53]), and thyroid (RR 2.73 [1.10-5.62]). SIC patients had a decreased risk of future lung cancer (RR 0.60 [0.41-0.83]). Compared to patients with only SIC, those in the pre-SIC group had a worse mean survival (57.9 vs 40.9 mos), both by K-M methods (p<0.001) and CPH models (HR 1.546 [1.420-1.683], p<0.001), controlling for age, year of diagnosis, race, sex, marital status, and stage. Compared to patients with only SIC, patients with an additional PM before and after the SIC had worse survival by K-M methods (p<0.001), but not when controlling for other variables (p=0.229). Patients in the post-SIC group did not have significantly different survival. In this post-SIC group, factors predictive of the future, non-SIC, primary were lower-stage SIC, increasing age, male sex, and earlier year of SIC diagnosis (all p<0.05). Conclusions: Almost one-third of patients with SIC have an associated metachronous primary tumor. When these primaries occur prior to (but not after) the SIC diagnosis, the prognosis is worse than with an initial SIC. The type of malignancies associated with SICs may guide future screening and surveillance efforts.