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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.