Efficacy and Safety of Peptide Receptor Radionuclide Therapy for the Treatment of Pancreatic Neuroendocrine Tumors: A Systematic Review and Meta-Analysis of Comparative Studies.

Abstract

Peptide receptor radionuclide therapy (PRRT) showed promising potential in the management of patients with pancreatic neuroendocrine tumors (pNETs). However, there is still a lack of evidence on its relative efficacy and safety compared with other treatment options. This review aims to synthesize the existing evidence on the efficacy and safety of PRRT for pNETs compared to different treatments. An electronic search was conducted from inception to May 2024. Comparative studies, including randomized controlled trials (RCTs), cohort studies, and case-control studies, that focused on the use of PRRT for treating pNETs were included. Efficacy outcomes included disease control rate (DCR), complete response (CR), partial response (PR), stable disease (SD), progression-free survival (PFS), and overall survival (OS). Safety outcomes were grade 3-4 hematological and renal toxicity and adverse events (AEs). Nine studies met the inclusive criteria. Among them, only one (11.1%) study was an RCT. Meta-analysis between full and reduced dosages of 177Lu-DOTATATE for G1-G2 pNETs revealed no significant differences in DCR, CR, PR, SD, and PFS between the groups. However, the full dosage group showed superior efficacy in some outcomes (DCR, CR, and PR). When PRRT was compared to other treatments such as surgery, chemotherapy, and targeted agents, it was associated with longer PFS and OS. Additionally, PRRT combined with capecitabine and salvage PRRT also showed efficacy in advanced cases. Safety analysis indicated that PRRT is well-tolerated, with minimal severe toxicity reported. PRRT is a promising therapeutic option for patients with advanced pNETs, offering a balance of efficacy and safety compared to other available treatments based on the low quality of evidence. Full-dosage PRRT may provide better outcomes than reduced dosages, and salvage PRRT remains effective for progressive disease. However, further high-quality RCTs are needed to confirm these findings and optimize PRRT usage in pNETs.