Summary Background: The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is increasing, but population registries seldom capture detailed clinical data. The Italian Association for Neuroendocrine Tumours (Itanet) established a nationwide prospective database to describe presentation, diagnostic pathways, management, and outcomes of newly diagnosed GEP-NENs in Italy. Methods: This multicentre prospective observational study enrolled 2138 consecutive patients with newly diagnosed GEP-NENs across 38 Italian centres (2019-2024). Clinical, pathological, imaging, and treatment data were prospectively collected and centrally validated. Descriptive and survival analyses were performed; Ki-67 was modelled as a continuous variable. Findings: Median age was 60.6 years, and 55.9% (1195/2138) were male. Tumours were well-differentiated NETs in 90.8% of patients (1942/2138), mainly of pancreatic (41.4%, 886/2138) or ileal (19.7%, 422/2138) origin. Median Ki-67 was 2%. An incidental diagnosis occurred in 58.6% (1254/2138) of cases. Among symptomatic patients, the mean diagnostic delay was 197 days (224 for pancreatic vs 184 for small bowel; p = 0.039). 68Ga-DOTA-peptide PET showed higher diagnostic yield than CT or MRI in small-bowel primaries (93.7% vs 83.1% vs 67.4%), whereas performance was similar in pancreatic tumours. Data on first-line treatment were available for 2050 patients. Initial management included surgery in 36.4% (746/2050), watchful waiting in 19.7% (404/2050), endoscopic resection in 7.7% (158/2050). Overall, 30.6% (627/2050) of patients received systemic therapy, most commonly somatostatin analogues in 23.7% (487/2050). Over a median follow-up of 271 days (IQR 121-530), 62 deaths were observed (event rate 4.9%). Overall survival differed markedly according to metastatic status and tumour grade. Ki-67 was prognostic when modelled continuously (p < 0.001), and a 15% cutoff identified poorer outcomes. Interpretation: This nationwide prospective study delineates real-world diagnostic and therapeutic patterns of GEP-NENs in Italy, confirms Ki-67 as a continuous prognostic biomarker, and identifies a 15% threshold associated with worse survival, providing a benchmark for outcome assessment and future clinical research. Funding: None.
Real-world presentation and outcomes of gastroenteropancreatic neuroendocrine neoplasms in Italy: findings from the nationwide Itanet prospective database / Panzuto, F., Rinzivillo, M., Partelli, S., Pusceddu, S., Campana, D., Spada, F., Della Vittoria Scarpati, G., Cives, M., Gelsomino, F., Bertuzzi, A.F., Marcucci, S., Badalamenti, G., Bergamo, F., Marini, M., Di Odoardo, A., Fazio, N., Tafuto, S., Lauricella, E., Coppa, J., Faggiano, A., et al.. - In: THE LANCET REGIONAL HEALTH. EUROPE. - ISSN 2666-7762. - 66:(2026). [Epub ahead of print] [10.1016/j.lanepe.2026.101684]
Real-world presentation and outcomes of gastroenteropancreatic neuroendocrine neoplasms in Italy: findings from the nationwide Itanet prospective database
Partelli S.;Fermi F.;Falconi M.;Massironi S.;
2026-01-01
Abstract
Summary Background: The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) is increasing, but population registries seldom capture detailed clinical data. The Italian Association for Neuroendocrine Tumours (Itanet) established a nationwide prospective database to describe presentation, diagnostic pathways, management, and outcomes of newly diagnosed GEP-NENs in Italy. Methods: This multicentre prospective observational study enrolled 2138 consecutive patients with newly diagnosed GEP-NENs across 38 Italian centres (2019-2024). Clinical, pathological, imaging, and treatment data were prospectively collected and centrally validated. Descriptive and survival analyses were performed; Ki-67 was modelled as a continuous variable. Findings: Median age was 60.6 years, and 55.9% (1195/2138) were male. Tumours were well-differentiated NETs in 90.8% of patients (1942/2138), mainly of pancreatic (41.4%, 886/2138) or ileal (19.7%, 422/2138) origin. Median Ki-67 was 2%. An incidental diagnosis occurred in 58.6% (1254/2138) of cases. Among symptomatic patients, the mean diagnostic delay was 197 days (224 for pancreatic vs 184 for small bowel; p = 0.039). 68Ga-DOTA-peptide PET showed higher diagnostic yield than CT or MRI in small-bowel primaries (93.7% vs 83.1% vs 67.4%), whereas performance was similar in pancreatic tumours. Data on first-line treatment were available for 2050 patients. Initial management included surgery in 36.4% (746/2050), watchful waiting in 19.7% (404/2050), endoscopic resection in 7.7% (158/2050). Overall, 30.6% (627/2050) of patients received systemic therapy, most commonly somatostatin analogues in 23.7% (487/2050). Over a median follow-up of 271 days (IQR 121-530), 62 deaths were observed (event rate 4.9%). Overall survival differed markedly according to metastatic status and tumour grade. Ki-67 was prognostic when modelled continuously (p < 0.001), and a 15% cutoff identified poorer outcomes. Interpretation: This nationwide prospective study delineates real-world diagnostic and therapeutic patterns of GEP-NENs in Italy, confirms Ki-67 as a continuous prognostic biomarker, and identifies a 15% threshold associated with worse survival, providing a benchmark for outcome assessment and future clinical research. Funding: None.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
