In an Australian phase III noninferiority trial reported in The Lancet Oncology, Buteau et al found that use of gallium-68–labeled PSMA-11 (Ga-68–PSMA-11) positron-emission tomography/computed tomography (PET/CT) could improve the pathway of diagnosis of prostate cancer in men with clinical high-risk but nonsuspicious or equivocal prostate MRI findings.
Study Details
In the multicenter trial, 660 men were randomly assigned between March 2022 and August 2025 to undergo Ga-68–PSMA-11 PET/CT (n = 331) or systematic transperineal prostate biopsy (n = 329). Patients were biopsy-naive with clinical suspicion of significant prostate cancer, equivocal (Prostate Imaging–Reporting and Data System [PI-RADS] 3) or nonsuspicious (PI-RADS 2) magnetic resonance imaging (MRI) but high clinical risk (eg, prostate-specific antigen [PSA] density > 0.1 ng/mL/mL, strong family history of prostate cancer, abnormal digital rectal examination, BRCA mutation, PSA > 10 ng/mL, PSA doubling time < 36 months, or PSA velocity > 0.75 ng/mL per year), PSA of 20 ng/mL or less, and clinical T2 disease or less. Patients with positive Ga-68–PSMA-11 PET/CT (PRIMARY score 3–5) underwent PSMA-PET–targeted transperineal prostate biopsy; those with negative findings (PRIMARY score 1–2) did not undergo biopsy. The co-primary outcomes were the proportion of patients with clinically significant prostate cancer (Gleason score of 3 + 4 [≥ 10% pattern 4] or higher) and the proportion of patients in the Ga-68–PSMA-11 PET/CT group who avoided biopsy within 6 months of random assignment.
Key Findings
The proportion of patients with clinically significant prostate cancer was 12% (39/331) in the Ga-68–PSMA-11 PET/CT group vs 16% (51/329) in the control group, with noninferiority being established (difference = –3.7%, 95% confidence interval [CI] = –8.9% to 1.5%, P = .0093 for noninferiority).
Use of Ga-68–PSMA-11 PET/CT avoided biopsy in 163 patients (49%) in the Ga-68–PSMA-11 PET/CT group (95% CI = 44%–55%, P < .0001 compared with 20% threshold).
After prostate biopsy, pain was reported by 21% of the Ga-68–PSMA-11 PET/CT group vs 21% of the control group, hematuria by 38% vs 43%, and hematospermia by 48% vs 45%.
The investigators concluded: “[Ga-68–PSMA-11 PET/CT] could have the potential to improve the diagnostic pathway of patients with a high clinical risk but nonsuspicious or equivocal prostate MRI. Further research, including health-economic analyses and validation with other PSMA radiopharmaceuticals, [is] needed to confirm the clinical implementation and generalisability of this approach.”
Michael S. Hofman, MBBS, of Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by the Prostate Cancer Foundation, National Health and Medical Research Council, St Vincent’s Curran Foundation, and Peter MacCallum Cancer Foundation. For full disclosures of the study authors, visit thelancet.com.
