Diagnostic accuracy of PSMA-targeted radioguided surgery in prostate cancer at multiple anatomical levels: a systematic review and meta-analysis

Background: Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (PSMA-RGS) is a promising intraoperative technique for improving lesion localization and surgical accuracy in prostate cancer (PCa), particularly in high-risk or recurrent cases. Objective: To systematically evaluate the diagnostic performance of PSMA-RGS in PCa using multilevel meta-analysis. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, and Web of Science for clinical studies published between January 2016 and May 2025, with the final search performed on May 1, 2025, and identified 28 eligible studies. Diagnostic accuracy was assessed at the patient, lesion, region, and lymph node levels, using pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios (DOR). Random-effects meta-analyses were conducted and risk of bias was evaluated with the ROBINS-I tool. Results: Ex vivo PSMA-RGS demonstrated the highest specificity (up to 100%), while in vivo PSMA-RGS showed excellent sensitivity (90–97%) and specificity (90–99%), particularly at the lymph node level. Across all evaluated anatomical levels, PSMA-RGS consistently outperformed preoperative imaging (log DOR: 5.77 vs. 2.99; p < 0.0001). All diagnostic results were confirmed by histopathology as the reference standard. Meta-regression identified in vivo PSMA-RGS, lymph node–based analysis, and γ-probes combined with high-purity germanium detectors—used for post-resection confirmation—as independent predictors of improved diagnostic performance. Conclusion: PSMA-RGS demonstrates robust diagnostic accuracy across multiple analytical levels, including per-patient, per-lesion, and per-node assessments. Initial evidence suggests that intraoperative γ-probes guidance may enable real-time localization of otherwise undetected nodal metastases. In high-risk prostate cancer surgery, this approach may help refine intraoperative decision-making, improve resection completeness, and reduce recurrence.