Abstract
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Prostate-specific membrane antigen (PSMA) PET/CT has transformed prostate cancer (PCa) management by improving lesion detection and guiding treatment decisions across disease stages. Following the first paper of the Italian PSMA Survey focused on technical aspects and primary staging, this second analysis explores its clinical use in PSA persistence after radical prostatectomy, biochemical recurrence (BCR), hormone-sensitive metastatic (mHSPC), and castration-resistant metastatic (mCRPC) settings.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A national cross-sectional survey was conducted jointly by five Italian scientific societies involving nuclear medicine physicians, medical oncologists, radiation oncologists, and urologists (AIMN, AIOM, AIRO, SIU, SIUrO) and the Meet-URO cooperative group. Dedicated sections addressed the adoption, timing, and perceived clinical impact of PSMA PET/CT in PSA persistence after radical prostatectomy, BCR, mHSPC, and mCRPC. Responses were analysed descriptively and stratified by medical competences (clinicians versus nuclear medicine physicians).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> PSMA PET/CT emerged as the preferred imaging modality in all clinical scenarios. In PSA persistence and BCR, 87–95% of respondents selected PSMA PET as first-line imaging, most often performed at PSA levels of 0.2–0.5 ng/mL. When negative, more than two-thirds recommended repeating PSMA PET/CT after PSA further rise. In mHSPC, over 80% of clinicians applied the CHAARTED criteria directly to PSMA PET findings, while PSMA PET/CT was also widely used for restaging and therapy monitoring. In mCRPC, PSMA PET/CT was routinely used for baseline and follow-up imaging. Most clinicians considered the low-dose CT component sufficient for radioligand therapy (RLT) eligibility, while [ <jats:sup>18</jats:sup> F]Fluorodeoxyglucose (FDG) PET was reserved for selected high-risk or discordant cases. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>PSMA PET/CT has become the central imaging modality in the management of advanced PCa in Italy. Its adoption has progressed faster than supporting evidence, underscoring the need for prospective validation, implementation of harmonised interpretation criteria, and unified national recommendations.</jats:p> </jats:sec>