Efficacy and safety of PRRT for the treatment of pancreatic neuroendocrine tumors: Systematic review and meta-analysis.

[BACKGROUND] PRRT showed promising potential in the management of patients with 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 (without SSA in key comparisons) for pNETs compared to different treatments.

[METHOD] An electronic search was conducted from inception to December 2024. Comparative studies including RCTs, cohorts and case-control studies focused on using PRRT in the treatment of pNETs were included. Efficacy outcomes included DCR, CR, PR, SD, PFS, and OS. Safety outcomes were grade 3-4 hematological and renal toxicity and overall AEs.

[RESULTS] Nine studies met the inclusive criteria. Among them, only one (11.1%) study is 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 suggested potential for improved OS in some studies, though not statistically significant. When PRRT was compared to other treatments such as surgery, chemotherapy, and targeted agents, it was associated with longer PFS and potentially 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.

[CONCLUSION] PRRT is a promising therapeutic option for patients with advanced pNETs, offering a balance of efficacy and safety compared to other available treatments. 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.