A PSMA-11 PET/CT scan with gallium Ga-68 led to the identification of more aggressive prostate cancer cells in men with equivocal or nonsuspicious findings on multiparametric MRI than a standard biopsy, according to first results from the phase III PRIMARY2 trial presented at the 2026 Annual Congress of the European Association of Urology (Abstract GC26-006).
The PSMA PET/CT scan resulted in half as many men requiring a biopsy than standard processes and reduced the diagnosis of insignificant prostate cancers without missing any clinically significant cancers.
“Getting told you have a risk of prostate cancer is a huge cause of anxiety and concern. Our findings show that PSMA PET/CT after MRI offers a 'belt and braces' approach that can determine which people have a clinically significant cancer, and which people are at low risk and don’t need a biopsy or further testing," said co-lead study author Louise Emmett, BSc(Hons), MBChB, FRACP, FAANMS, MD, Director of Theranostics and Nuclear Medicine at St Vincent's Hospital, Sydney. "PRIMARY2 is the largest of a series of studies undertaken by this group, exploring whether PSMA PET/CT scanning could improve prostate cancer diagnosis and reduce unnecessary biopsies for patients.”
Background and Study Methods
The investigator-initiated, multicenter, randomized, controlled phase III PRIMARY2 trial enrolled 660 men from across seven Australian hospitals who had a prostate-specific antigen level below 20 ng/mL and PI-RADS 2 with high clinical risk or PI-RADS 3 who had not yet undergone a biopsy. Patients were randomly assigned 1:1 to either pelvic-only Ga-68-PSMA-11 PET/CT scan or systemic transperineal prostate biopsy. In the investigational arm, if results of the PSMA PET/CT scan were positive, patients underwent a targeted biopsy, and if results were negative patients could avoid a biopsy.
“PSMA PET/CT scanning makes prostate cancer cells light up in a remarkable way, particularly in more aggressive cancers. It’s rare to see such strong imaging that could be so powerful in the clinic. Incorporating this testing into clinical care could help to address the major challenge of prostate cancer overdiagnosis, which leads to at best unnecessary and at worst harmful treatment for cancers that would never cause any harm,” said presenting author James Buteau, MD, FRACP, FRCPC, Nuclear Medicine Physician at Peter MacCallum Cancer Centre.
The coprimary endpoints were the proportion of patients with clinically significant prostate cancer and proportion of patients in the PSMA PET/CT arm who could avoid biopsy. A key secondary endpoint was the proportion of patients with clinically insignificant prostate cancer.
Key Findings
In the PSMA PET/CT arm, 49% of patients were able to avoid biopsy (95% confidence interval [CI] = 44%–55%; P < .0001).
In the control arm, 16% of patients had significant prostate cancer, which was considered a Gleason score of seven or higher, compared with 12% in the investigational arm, for a difference of –3.7% (95% CI = –8.0% to 1.5%; P = .0093). The proportion of patients with a Gleason score of 4 + 3 or higher was 4.8% in the control arm and 4.2% in the investigational arm. The rate of insignificant prostate cancer was 32% in the biopsy arm and 14% in the PSMA PET/CT arm, for a difference of –18% (97.5% CI = –25% to –11%; P < .0001).
“This well-conducted trial shows that incorporating PSMA PET/CT in men with low or intermediate risk lesions—defined by MRI as PI-RADS 2 or 3—significantly reduced the number of unnecessary biopsies and the diagnosis of clinically insignificant prostate cancer. Importantly, this didn’t compromise the detection of clinically significant disease," stated Derya Tilki, MD, Member of the EAU Scientific Congress Office and a Senior Consultant Urologist at Martini-Klinik Prostate Cancer Center, Germany. "These results support consideration of PSMA PET/CT in the diagnostic work-up of appropriately selected patients. I congratulate the investigators on their study.”
DISCLOSURES: The PRIMARY2 trial is sponsored by the Peter MacCallum Cancer Centre, co-led with St Vincent’s Hospital, Sydney. The study is funded by the U.S. Prostate Cancer Foundation, supporting both the Prostate Cancer Theranostics Imaging Centre of Excellence and Louise Emmett, St Vincent’s Hospital Curran Foundation, Peter MacCallum Cancer Foundation, National Health and Medical Research Council, and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. For full disclosures of the study authors, visit urosource.uroweb.org.
