Prostate-specific membrane antigen (PSMA) radioguided surgery in prostate cancer: An overview of current application and future perspectives

Radical prostatectomy (RP) with or without pelvic lymph node dissection (PLND) is the most frequent approach to treat men affected by prostate cancer (PCa), together with primary radiotherapy. Generally, patients performed computed tomography (CT) and bone scintigraphy to stage the disease prior to surgery. However, specific inhibitors directed to the prostate-specific membrane antigen (PSMA) have been recently proposed as radiopharmaceutical for positron emission tomography (PET) imaging. PSMA-PET proved higher diagnostic accuracy to stage high-risk PCa compared to conventional imaging, even if its impact on overall survival is yet to be confirmed. One of the main limitations for PSMA-PET in staging PCa is represented by the low sensitivity in identifying metastatic lymph node, namely in case of nodes smaller than 4–5 mm. Radioguided surgery (RGS) is based on the intraoperative detection of radiation emitted by the specific radiopharmaceutical. Recently, the possibility of performing RGS using cancer-specific radiotracer with high diagnostic accuracy (e.g. PSMA inhibitors) gained attention. In this review, we aimed to explore the value of PSMA-RGS in PCa, aimed at improving the surgery accuracy to remove nodal metastasis. Furthermore, we evaluated different radiation detectors (gamma rays probes vs. beta positron probes) and the diagnostic accuracy of these probes compared to PSMA-PET. A comprehensive literature review was performed in December 2022 with a non-systematic approach. After the first literature screening, a total of 16 studies have been selected and a comprehensive qualitative narrative synthesis of the articles has been performed. First studies showed promising results for PSMA-RGS, and prospective trials demonstrated good concordance of in vivo PSMA-positive detected nodes with histopathology analysis of the specimens. High sensitivity and specificity of the RGS approach were found. Whilst gamma probes have been more broadly explored, the clinical use of beta probes has been tested in feasibility studies only. Finally, Cerenkov luminescence imaging, micro-image guidance and augmented reality/virtual reality approaches in surgery are currently rising attention and are generating future perspectives for PSMA-guided surgery in PCa.