Abstract
BACKGROUND: Gastrin-releasing peptide receptor (GRPR)-targeting radiopharmaceuticals are being developed for diagnostic and therapeutic applications in prostate cancer. This systematic review and meta-analysis aimed to synthesize available evidence regarding the diagnostic performance of GRPR-targeted positron-emission tomography (PET) in biochemically recurrent prostate cancer. METHODS: A comprehensive literature search was performed using appropriate keywords search strings formulated with Boolean syntax in the PubMed, Embase and Cochrane Library. Articles related to GRPR-targeted PET in biochemically recurrent prostate cancer were included, covering publications available up to May 1, 2025. A meta-analysis with a random-effects model was used to estimate overall and subgroup-specific pooled detection rate (DR). The literature quality was determined by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A sensitivity analysis using leave-one-out method was performed to evaluate the potential bias. RESULTS: Out of 469 articles, 212 underwent full-text screening and 6 articles with 278 patients were finally included. The overall DR of GRPR-targeted PET for biochemical recurrence (BCR) was 0.68 [95% confidence interval (CI): 0.6-0.75]. Four studies reported the pooled DRs stratified by serum prostate-specific antigen (PSA) levels: 0.38 (95% CI: 0.25-0.51) for PSA <0.5 ng/mL stratum, 0.69 (95% CI: 0.53-0.85) for PSA 0.5 to <1.0 ng/mL stratum, 0.61 (95% CI: 0.43-0.79) for PSA 1.0 to <2.0 ng/mL stratum, 0.75 (95% CI: 0.58-0.91) for PSA 2.0 to <5.0 ng/mL stratum, 0.72 (95% CI: 0.60-0.84) for PSA ≥5.0 ng/mL stratum, respectively. CONCLUSIONS: In the present meta-analysis, GRPR-targeted PET has comparable and promising diagnostic utility for BCR of prostate cancer compared to prostate-specific membrane antigen (PSMA) and conventional imaging. Nevertheless, the limited sample sizes of existing studies warrant large-sample prospective trials comparing GRPR-targeted PET with first-line modalities to validate its clinical diagnostic and therapeutic value.