Prostate cancer (PCa) was estimated to account for 28% of all cancer cases in men in Australia last year. In primary staging, PSMA PET/CT has emerged as a highly sensitive imaging modality compared to conventional imaging. While its utility in high-risk prostate cancer is well-established, its role in intermediate-risk patients is less clear. Importantly, the Australian Federal Government has recently announced the MBS will fund a whole body PSMA PET/CT for primary staging in men with both intermediate or high-risk PCa. However, as per the European Association of Urology guidelines, there is insufficient evidence regarding the utility of this imaging modality in men with intermediate-risk PCa. This discrepancy highlights the need to further assess the clinical utility of PSMA PET/CT in this patient subgroup. Patients with high-risk PCa will likely receive treatment; however, guideline management of intermediate-risk PCa is less structured and the possibility of overtreatment exists. Precise imaging techniques in staging can also assist in intermediate-risk PCa where patients can be offered active surveillance, minimising harm.

A systematic search of electronic databases, including CINAHL, EMBASE and MEDLINE, was conducted in March 2025 looking for relevant studies evaluating the utility of PSMA PET/CT in the primary staging of newly diagnosed Gleason 7, intermediate-risk or ISUP Grade 2 or 3 PCa. Studies were only included if data was stratified to accurately determine positive PSMA PET/CT on primary staging in intermediate-risk, Gleason 7, or ISUP Grade 2 or 3 PCa.

Overall, we found 14 studies that detected positive metastases by PSMA PET/CT in this patient subgroup. PSMA PET/CT positivity for extra-prostatic disease in this subgroup ranged from 2.2%-38.9%. Further, in ISUP Grade 2 PCa this ranged from 2.2-21.4% compared to 13.6-33.3% in ISUP Grade 3 PCa across 2 studies (Figure 1), suggesting the use of PSMA PET/CT for primary staging may provide more utility in unfavourable-intermediate risk PCa. However, this evidence is limited by many factors including low statistical power, retrospective analyses and lack of histopathological confirmation.

The key findings of this review are as follows: 1) PSMA PET/CT has low yield for primary staging in favourable intermediate-risk PCa, and 2) insufficient evidence exists to support the use of PSMA PET/CT for primary staging in both favourable and unfavourable intermediate-risk PCa. It is clear from the literature that we need prospective data to validate the findings of retrospective studies, which suggest that the yield of PSMA PET/CT in ISUP Grade 2 PCa is low, compared to ISUP Grade 3.