Recommendations for selection, treatment, and follow‑up in peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors: a Delphi consensus from the Galician Multidisciplinary Group on Neuroendocrine and Endocrine Tumors (GGNET)

Abstract

Background: Peptide receptor radionuclide therapy (PRRT) is an established treatment for patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors (SSTR). Despite robust trial and real-world data, heterogeneity persists regarding patient selection, therapeutic sequencing, and follow-up strategies.

Methods: A Delphi consensus was conducted by the Galician Multidisciplinary Group on Neuroendocrine and Endocrine Tumors (GGNET). Ten experts in oncology, endocrinology, nuclear medicine, and radiology participated. 29 clinical statements were developed after a systematic review and rated using a 4-point Likert scale. Consensus was defined as ≥ 70% agreement.

Results: Consensus (defined a priori as ≥ 70% agreement) was achieved for all statements although the level of agreement varied across domains. PRRT was endorsed for patients with unresectable or metastatic, progressive, well-differentiated GEP-NETs (grades 1-3, Ki-67 ≤ 55%) with confirmed SSTR expression. SSTR-targeted imaging (PET or scintigraphy) was considered mandatory for eligibility, with PET identified as the preferred modality. [18F]-FDG-PET was recommended selectively as a complementary prognostic tool in higher-grade tumors, rapid progression, or discordant imaging. Multidisciplinary tumor board review was universally supported. Guidance was provided on treatment administration, including standard dosing, renal protection, hematologic monitoring, and individualized risk assessment. Routine interim imaging was not recommended. Structured follow-up with CT/MRI was endorsed, with indication-driven use of SSTR or FDG-PET and limited routine value of non-specific biomarkers. Functional biomarkers, such as 5-HIAA and peptide hormones, retained utility in functioning tumors.

Conclusions: This Delphi consensus provides pragmatic, multidisciplinary, and evidence-informed guidance to harmonize routine clinical practice in the use of PRRT for well-differentiated, SSTR-positive NETs. The proposed statements and the algorithm aim to harmonize practice across centers, reduce variability in care, enhance safety, and ultimately improve patient outcomes.

Keywords: Delphi consensus; Follow-up; Neuroendocrine tumors; PET SSTR; PRRT; Somatostatin receptors; [177Lu]Lu-DOTA-TATE.