The Role of Radioligand Therapy in Gastroenteropancreatic Neuroendocrine Tumors: An Italian Expert Opinion

Salvatore Tafuto, Secondo Lastoria, Francesco Panzuto, Lorenzo Antonuzzo, Davide Campana, Sara Cingarlini, Mauro Cives, Diego Ferone, Angelina Filice, Dario Giuffrida, Marco Maccauro, Stefano Partelli, Nicola Fazio (2025) The Role of Radioligand Therapy in Gastroenteropancreatic Neuroendocrine Tumors: An Italian Expert Opinion Adv Ther (IF: 4) 42(12) 5931-5949

Abstract

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) comprise a heterogeneous group of clinically diverse tumors; their management is based on clinical characteristics. International guidelines recommend standard-dose somatostatin analogues (SSAs) as first-line treatment for advanced, low-grade G1 and "low" G2 NETs. No standard-of-care treatment is determined for "high" G2 and G3 NETs. Radioligand therapy (RLT) with [177Lu]Lu-DOTA-TATE was authorized to treat well-differentiated (G1 and G2) unresectable or metastatic, somatostatin receptor (SSTR)-positive GEP-NETs, in progression after SSA. Recently published NETTER-2 is the first randomized clinical trial to demonstrate the efficacy and safety of [177Lu]Lu-DOTA-TATE as first-line treatment in patients with newly diagnosed, advanced "high" G2 and G3 GEP-NETs. In February 2024, 13 scientific board members discussed RLT guidelines and treatment perspectives in patients with GEP-NETs based on NETTER-2 outcomes. In their opinion, NETTER-2 will impact first-line treatment choice in patients with G2 SSTR-positive GEP-NETs. RLT as first-line treatment could reduce tumor burden rather than maintain stable disease, except in patients who are highly symptomatic where chemotherapy should be considered. In patients with G3 SSTR-positive GEP-NETs, NETTER-2 strongly supports RLT as potential first-line treatment. RLT could also have a significant role in a perioperative setting for those cases with borderline resectable disease or advanced oligometastatic disease. The results of NETTER-2 confirm that therapy selection should be guided by symptoms, syndrome, and functional expression of SSTR within the tumor site(s) rather than GEP-NET histology and grading. Thus, the scientific board agreed that RLT should always be considered in SSTR-positive GEP-NETs. Graphical Abstract available for this article.© 2025. The Author(s).

Links

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12618337
http://www.ncbi.nlm.nih.gov/pubmed/41082075
http://dx.doi.org/10.1007/s12325-025-03383-5

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