Natural history of gastro-entero-pancreatic and thoracic neuroendocrine tumors. Data from a large prospective and retrospective Italian Epidemiological study: THE NET MANAGEMENT STUDY

Background: The few epidemiological data available in literature on neuroendocrine tumors (NET)s are mainly based on Registry databases, missing therefore details on their clinical and natural history. Aim: To investigate epidemiology, clinical presentation and natural history of NETs Design & Setting: A large national retrospective survey was conducted in 13 Italian referral centers. Among 1203 NETs, 820 originating in the thorax (T-NET), in the gastro-enteropancreatic tract (GEP-NET) or metastatic NET of unknown primary origin (U-NET) were enrolled in the study. Results: 93% had a sporadic and 7% a MEN1 associated tumor. 63% were GEP-NET, 33% T-NET, 4% U-NET. Pancreas and lung were the commonest primary sites. Poorly differentiated carcinomas were <10%, all sporadic. The incidence of NET had a linear increase from 1990 to 2007 in all the centers. The mean age at diagnosis was 60.0±16.4 yrs, significantly anticipated in MEN1 patients (47.7±16.5 yrs). Association with Cigarette smoking and other non-NET cancer were more prevalent than in the general Italian population. The first symptoms of the disease were related to tumor burden in 46%, endocrine syndrome in 23%, while the diagnosis was fortuity in 29%. Insulin (37%) and serotonin (35%) were the most common hormonal hypersecretions. An advanced tumor stage was found in 42%, more frequently in the gut and thymus. No differences in the overall survival was observed between TNET and GEP-NET and between sporadic and MEN-1 associated tumors at ten years from diagnosis, while survival probability was dramatically reduced in U-NET. Conclusions: The data obtained from this study furnish relevant information on epidemiology, natural history and clinico-pathological features of NET, not available from the few published Register studies.