Efficacy and safety of [¹⁷⁷Lu]Lu-DOTA-TATE versus standard systemic therapies in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors: a retrospective cohort study

Advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) present a therapeutic challenge due to their heterogeneity and variable response to systemic therapies. This study aimed to evaluate the real-world efficacy and safety of peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTA-TATE in patients with advanced well-differentiated GEP-NETs. This retrospective cohort study included 129 patients diagnosed with advanced well-differentiated GEP-NETs between January 2022 and December 2025. Patients were classified into two groups according to treatment strategy: the [¹⁷⁷Lu]Lu-DOTA-TATE group ( n = 65) and the control group ( n = 64), who received standard systemic therapies without PRRT. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. Prognostic factors for OS and PFS were evaluated using Cox regression analyses. The median duration of follow-up was 34.6 months (1.3–45.7) in the [¹⁷⁷Lu]Lu-DOTA-TATE group and 25.8 months (0.9–45.6) in the control group. The [¹⁷⁷Lu]Lu-DOTA-TATE group demonstrated significantly longer median OS (34.6 vs. 25.8 months; P = 0.046) and median PFS (22.0 vs. 16.7 months; P = 0.008) compared with the control group. ORR showed a trend toward improvement ( P = 0.118), while DCR was significantly higher in the [¹⁷⁷Lu]Lu-DOTA-TATE group ( P = 0.026). The overall incidence of adverse events and the rates of grade ≥ 3 adverse events were comparable between groups ( P > 0.05). Multivariable analysis identified [¹⁷⁷Lu]Lu-DOTA-TATE treatment, younger age, lower Ki-67 index, and lower tumor grade as independent predictors of improved OS or PFS. [¹⁷⁷Lu]Lu-DOTA-TATE provides meaningful survival benefits with acceptable safety in patients with advanced well-differentiated GEP-NETs, supporting its integration into real-world treatment strategies and warranting further prospective validation.