PSMA PET/CT in contemporary prostate cancer management: From initial staging to biochemical recurrence

Prostate-Specific Membrane Antigen (PSMA) PET/CT has rapidly become the preferred first-line imaging modality for primary staging of unfavourable intermediate-risk, high-risk, and very high-risk prostate cancer, and for restaging at biochemical recurrence. The objective of this review is to provide nuclear medicine physicians with a comprehensive and practical framework for PSMA PET/CT interpretation, structured reporting, and clinical decision integration, with emphasis on primary staging evidence, biochemical recurrence (BCR) detection rates, imaging pitfalls, and the PSMA-RADS reporting system.

A narrative review of published evidence was performed, encompassing landmark randomised controlled trials and guideline documents from the EAU, EANM, and NCCN. Key trials reviewed included proPSMA, OSPREY, PRIMARY, CONDOR, and VISION.

PSMA PET/CT demonstrated diagnostic accuracy (AUC) of 0.92 versus 0.38 for conventional imaging in primary staging (proPSMA). Detection rates in BCR ranged from 38% at PSA <0.2ng/mL to 97% at PSA >2ng/mL. In a phase 3 RCT, ¹⁸F-PSMA-1007 demonstrated superiority over ¹⁸F-Choline (84% vs 69%, OR 2.53, p<0.001).

PSMA PET/CT provides superior staging accuracy, enables detection of recurrence at low PSA levels, guides oligometastasis-directed therapy, and serves as the mandatory gatekeeper for ¹⁷⁷Lu-PSMA-617 theranostic eligibility. Structured reporting using PSMA-RADS and rigorous CT correlation - particularly to exclude unspecific bone uptakes (UBUs) with ¹⁸F-PSMA-1007 - are core professional competencies of the nuclear medicine physician.