The role of PSMA PET/CT in staging patients with intermediate-risk prostate cancer

To synthesise data evaluating the diagnostic utility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in intermediate-risk prostate cancer (PCa), as its role in intermediate-risk PCa remains uncertain.

A systematic search was conducted for studies evaluating PSMA PET/CT in primary staging of newly diagnosed European Association of Urology (EAU)/National Comprehensive Cancer Network (NCCN) intermediate-risk, or Gleason Score 7 (International Society of Urological Pathology [ISUP] Grade Group [GG] 2-3) PCa. The primary outcome was overall positive scans (lymph nodes or distant metastases). We also secondarily analysed diagnostic accuracy measuring sensitivity, specificity, positive predictive value, and negative predictive value.

In total, 16 studies reported positivity rates ranging from 2.2% to 50.0% in intermediate-risk PCa. A pooled analysis of 13 studies found a PSMA PET/CT positivity rate of 9% (95% confidence interval [CI] 6-11%). In ISUP GG 2 PCa, positivity ranged from 2.2% to 21.4%, compared to 13.6-33.3% in ISUP GG 3 PCa (across two studies). The overall nodal and metastatic sensitivity of PSMA PET/CT was low in intermediate-risk men, 33% (95% CI 14-60%). Limitations included small sample sizes, retrospective designs, and limited histopathological confirmation.

For primary staging in intermediate-risk PCa PSMA PET/CT showed a low yield. Limited data exist to guide its use in favourable vs unfavourable subgroups. Robust, prospective studies are needed to define its role in clinical decision-making, further prognostic benefits, and to inform future guidelines.