[177Lu]Lu-DOTA-TATE PRRT extends survival in oligodiscordant GEP-NETs, achieving median OS of 27.3 months.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are often treated with peptide receptor radionuclide therapy (PRRT) using somatostatin analogues (SSA) like [177Lu]Lu-DOTA-TATE after progression. Landmark trials like NETTER-1 and NETTER-2 established PRRT for lesions with uniform SSTR expression. However, a critical gap exists for patients with oligodiscordant disease, characterized by up to three lesions that are FDG avid but lack DOTATATE avidity on dual PET imaging. This subgroup currently lacks data on PRRT efficacy, leaving treatment decisions uncertain and potentially limiting access to this effective therapy.

This single-center retrospective review analyzed 13 patients with advanced GEP-NETs and oligodiscordant disease who received at least one cycle of PRRT with [177Lu]Lu-DOTA-TATE between 2020 and 2024. Safety was evaluated using CTCAE v5.0 for renal and hematological parameters during and 3 months post-treatment. Treatment response was assessed via molecular imaging with Gallium-68 DOTATATE PET/CT. The Kaplan-Meier method was employed to determine median progression-free survival (PFS), overall survival (OS), and time to next treatment (TTNT).

Among the 13 patients (median age 66 years, 54% male), primary tumor sites included small bowel (7), pancreas (4), and colorectal (2), with 10 cases of WHO grade 2 and 3 cases of grade 3 disease. No patients had grade 1 disease.

The median overall survival (OS) for this cohort was 27.3 months (95% CI 19.7 - not reached), demonstrating significant longevity in a challenging patient population. Median progression-free survival (PFS) was 15.1 months (95% CI 7.1-20.1). These outcomes suggest that PRRT with [177Lu]Lu-DOTA-TATE can confer substantial clinical benefit even in patients with oligodiscordant GEP-NETs, a group previously excluded from standard PRRT protocols due to mixed imaging characteristics.