Background <p>The use of peptide receptor radionuclide therapy (PRRT) is well established in the treatment of advanced or unresectable neuroendocrine tumours (NETs) after progression on somatostatin analogues (SSA), with randomised clinical trials such as NETTER-1 and NETTER-2 showing improvement in progression free survival (PFS) as well as tumour response [12, 13]. Current landmark trials only considered patients suitable for PRRT if all known lesions displayed SSTR expression, via avidity on planar scintigraphy or Gallium-68 DOTATATE PET/CT. However, there is a select group of patients with oligodiscordant disease (3 or less lesions which are FDG avid but not DOTATATE avid) on dual DOTATATE/FDG PET imaging who may benefit from PRRT in combination with additional therapies such as liver directed therapy (LDT) or chemotherapy. There is currently no data regarding the efficacy and outcomes of PRRT in oligodiscordant disease. This study is the first to describe the treatment patterns and outcomes of patients with oligodiscordant disease receiving PRRT.</p> Methods <p>A single-centre retrospective review was performed in patients with advanced gastroenteropancreatic NETs with oligodiscordant disease who received at least one cycle of PRRT with [177Lu]Lu–DOTA-TATE from 2020 to 2024. Safety was assessed by renal and haematological parameters (CTCAE v5.0) during PRRT, and at 3 months post completion of treatment. Response to treatment was evaluated on molecular imaging with Gallium-68 DOTATATE PET/CT. Kaplan-Meier method was used to perform median progression free survival (PFS), overall survival (OS), and time to next treatment (TTNT) analyses.</p> Results <p>Thirteen patients met the inclusion criteria, the median age was 66 years, and 54% were male. Primary site: small bowel (7), pancreas (4), colorectal (2). WHO grade: none had grade 1 disease, ten grade 2 and three had grade 3 disease. Median OS was 27.3 months (95% CI 19.7 - not reached), median PFS 15.1 months (95% CI 7.1–20.1), and median TTNT 15.0 months (95% CI 6.7–39.6). One of 15 patients developed treatment related myeloid neoplasm on long term follow-up, confirmed by bone marrow biopsy. No patients developed significant renal toxicity on follow-up.</p> Conclusion <p>In patients with advanced NETs with oligodiscordant disease identified on dual PET imaging, the combination of PRRT with systemic therapy or other therapies (surgery, liver directed therapy, radiotherapy) can be effective with acceptable toxicity and should be considered as a possible option for treatment in selected patients. The sequencing of treatment modalities and exact strategy employed is best decided at an experienced NET centre with multi-disciplinary input. Keywords: Neuroendocrine tumours, FDG PET, Dotatate PET, Peptide receptor radionuclide therapy, Discordant disease, Overall survival, Progression free survival, FDG avid disease </p>