{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:45:43Z","timestamp":1792449943387,"version":"4.5.0"},"reference-count":87,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Grade 3 neuroendocrine tumours (NET G3) represent approximately 20% of high\u2010grade neuroendocrine neoplasms, and the recent identification of this entity has given rise to many unanswered questions relating to clinical management. The prognosis for these patients is worse than for those with Grade 1\u20132 well\u2010differentiated NET, but better than for those with Grade 3 poorly differentiated neuroendocrine carcinoma. This consensus statement aims to address some uncertainties and explore unmet needs in the management of patients with NET G3. Firstly, the role of surgery in localised disease will be discussed as well as the dilemma in relation to the use of neo\u2010adjuvant and\/or adjuvant treatment in this setting. Treatment of oligometastatic digestive NET G3 will also be examined, including the positioning of surgery and ablative therapy. In the advanced setting, traditionally, chemotherapy in the form of temozolomide\/capecitabine or 5\u2010fluorouracil\u2010based therapies, rather than platinum\/etoposide, is considered a first\u2010line treatment option, with second\u2010line therapy dependent on what was used first\u2010line. More recently, following the results of the NETTER\u20102 trial, Peptide Receptor Radionuclide Therapy with\n                    <jats:sup>177<\/jats:sup>\n                    Lu\u2010DOTATATE may be an option for selected patients with somatostatin receptor positive NET G3. There is limited data on the use of immunotherapy and targeted therapy in this disease group to date, and some available evidence will be presented. The role for re\u2010biopsy to guide treatment decision\u2010making in patients with digestive NET G3 and whether NET G3 outside of the digestive tract should be treated similarly will also be scrutinised. Prospective studies with translational end\u2010points are required to enable a better understanding of this diagnosis and to facilitate more optimal treatment discoveries.\n                  <\/jats:p>","DOI":"10.1111\/jne.70080","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T10:45:14Z","timestamp":1754736314000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Controversies in\n                    <scp>NEN<\/scp>\n                    : An\n                    <scp>ENETS<\/scp>\n                    position statement on the treatment of patients with Grade 3 well\u2010differentiated neuroendocrine tumours of the gastro\u2010enteropancreatic tract"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-3678","authenticated-orcid":false,"given":"Mair\u00e9ad G.","family":"McNamara","sequence":"first","affiliation":[{"name":"Division of Cancer Sciences University of Manchester  Manchester UK"},{"name":"Department of Medical Oncology The Christie NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7132-6214","authenticated-orcid":false,"given":"Halfdan","family":"Sorbye","sequence":"additional","affiliation":[{"name":"Cancer Clinic Haukeland University Hospital  Bergen Norway"},{"name":"Department of Clinical Science University of Bergen  Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehara","family":"Begum","sequence":"additional","affiliation":[{"name":"Department for General\u2010, Visceral\u2010, Thoracic\u2010 and Endocrine Surgery, ENETS\u2010Center of Excellence, Johannes\u2010Wesling\u2010Klinikum Minden University Hospital of the Ruhr\u2010University Bochum  Minden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuel","family":"Christ","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetology and Metabolism University Hospital of Basel  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6869-0704","authenticated-orcid":false,"given":"Nicola","family":"Fazio","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors IEO IRCCS, European Institute of Oncology  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynnette","family":"Fernandez\u2010Cuesta","sequence":"additional","affiliation":[{"name":"Computational Cancer Genomics Team, Genomic Epidemiology Branch International Agency for Research on Cancer (IARC\u2010WHO)  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocio","family":"Garcia\u2010Carbonero","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Universitario 12 de Octubre, IIS Imas12, Facultad de Medicina Universidad Complutense de Madrid (UCM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Kaltsas","sequence":"additional","affiliation":[{"name":"1st Propaedeutic Department of Internal Medicine National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Kasajima","sequence":"additional","affiliation":[{"name":"Department of Pathology, TUM School of Medicine and Health Technical University Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Salazar","sequence":"additional","affiliation":[{"name":"Medical Oncology Department Institut Catal\u00e0 d'Oncologia. 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