669 EUS Is Not Essential Method Before Endoscopic Treatment of Small Recta NETs

BACKGROUND: SI-NETs are rare, indolent, and difficult to diagnose. As a result, patients present late with advanced surgically-incurable disease (dz) and a low 5-year survival rate. Reports of families with ≥2 affected members with multiple primary carcinoid tumors suggest the presence of a familial and possibly hereditary form, in addition to what is generally considered a sporadic dz. Recognition of a familial form of a slow growing tumor and the benefit of early detection of an otherwise treatment-resistant dz suggests that screening may improve dz outcome. AIMS: To prospectively determine whether screening families with SI-NET can detect occult tumor at an early stage and whether surgical intervention can alter the dz outcome. METHODS: A single-center prospective study was conducted from 2008 to 2014 to evaluate asx members of families with ≥2 previously diagnosed (symptomatic, sx) SI-NET cases. Families with other hereditary cancer syndromes were excluded. Asymptomatic (asx) members were screened with biochemical markers (CgA, serotonin, 5-HIAA) and imaging (18-FDOPA PET/CT, CT C/A/P with IV contrast, capsule endoscopy). Positively screened patients underwent ex lap and intraop U/S. Living previously diagnosed sx cases were similarly evaluated or if deceased, by medical records. RESULTS: 15 families with 81 sx cases (mean age 61.0 years; 53% female) and 151 asx members (mean age 52.7 years; 56% female) were evaluated. 36 (24%) asx members (mean age 57.8 years) screened positive. 32 elected for surgery, and 29 had jejunal/ileal carcinoid tumors. Compared to their sx relatives, mean tumor number was 6.5 vs. 6.7, and mean bowel resection was 72.9 vs. 60.6 cm, with the majority having well-differentiated (97% vs. 79% grade I) and multi-focal primary disease (79% vs. 68%) (all p>0.05). Asx members had smaller tumors (mean 8.7 vs. 18.6 mm), earlier disease (7% vs. 68% stage IV), and less nodal involvement (46% vs. 92%) (all p<0.001). All 29 positively screened and surgically confirmed members remain asx, and 27 (93%) have no evidence of dz with a mean follow-up of 39 months. In contrast, 39 (47%) sx deceased relatives had a mean survival of 5.4 yrs, and 42 (53%) are living with disease for 4.4 yrs. Of the 42 living sx relatives, 39 (93%) have stage IIIB (38%) or stage IV (55%) disease. CONCLUSIONS: Asx members of families with ≥2 SI-NET cases are at high risk for occult tumors. Screening detects occult tumors at an early stage. Surgery improves the natural history and may prove to be curative in most cases. Multiple primary tumors appear to be a feature of familial dz and may represent germline/hereditary origin in some families. A careful family history and possibly screening should be performed in families of patients found to have multiple primary SI-NETs.