To systematically review the prospective literature on the role of 68Ga and 18F PSMA PET/CT and PET/MRI as a tool for functional imaging in prostate cancer biochemical recurrence (BCR), particularly with respect to detection efficacy and impact on management.

We performed a systematic literature search using PubMed in July 2021, focusing on original prospective studies looking at PSMA PET/CT and PET/MRI in BCR.

We included 20 prospective studies reporting on 68Ga and 18F PSMA PET/CT and PET/MRI. Pooled PSMA PET positivity was 66.6% out of 2110 patients. The only factor consistently reported as associated with PSMA PET positivity was PSA level at the time of the study. Analysis of PSMA PET positivity rates in differing PSA ranges confirmed increasing positivity with increasing PSA levels. No significant adverse reactions were reported in the 20 studies, but only 6 studies mentioned safety or adverse reactions. A major change of management occurred in 42.7% of all patients scanned with PSMA PET/CT and more specifically 63.2% of those patients positive on PSMA PET/CT. There are no long-term studies that prove a survival benefit from these changes in management.

There is prospective evidence for efficacy of PSMA PET/CT and PET/MRI in localizing disease recurrence in BCR, which increases with increasing PSA level at the time of scanning. There are no reported significant adverse effects related to the PSMA PET ligands. There is evidence of major change in management but no evidence for whether this achieves any improvement in outcome.