Peptide receptor radionuclide therapy (PRRT) in high grade neuroendocrine neoplasms: a systematic review and meta-analysis

Purpose: We performed a systematic review and meta-analysis to investigate the efficacy of peptide receptor radionuclide therapy (PRRT) by using radiolabeled somatostatin analogues in high grade gastro-entero-pancreatic neoplasms (GEP-NEN). Methods: All clinical studies published up to March 2025, including patients with grade 3 (G3) GEP-NEN treated with [177Lu] Lu-DOTA-TATE and/or [90Y] Y-SSA, were identified based on systematic searches in the PubMed and Embase databases. Eligible studies had to report at least one of the following outcomes: 1) response to therapy evaluated according to RECIST (version 1.1 as complete response, partial response, stable disease, progressive disease; 2) median progression free survival (PFS) with 95% confidence intervals (CI); 3) median overall survival (OS) with 95% CI. Objective response rate (ORR) and disease control rate (DCR) were considered as primary outcomes. Results: The final analysis included 7 studies accounting for a total of 317 patients with G3 disease (ranging from 18 to 112). Six studies evaluated response to therapy according to RECIST in 288 patients, and in 4 of them patients were also stratified according to ki67 values. The pooled ORR and DCR were 34% (95% CI: 22-46) and 64% (95% CI: 52-76), respectively. The funnel plot indicated no publication bias among these studies. Five studies reported in 239 patients median PFS with 95% CI, with a pooled estimate of 13.88 (95% CI: 10.33-18.64) months. Three studies fully reported in 174 patients median OS with 95% CI, with a pooled estimate of 29.95 (95% CI: 19.80-45.30) months. Conclusions: In patients with G3 GEP-NEN, PRRT may provide substantial disease control and response rates, and it seems able to delay the progression of the disease.