PRIMARY2 trial supports PSMA PET-CT in equivocal prostate MRI work-up

Adding prostate-specific membrane antigen (PSMA) PET-CT to the diagnostic pathway for men with normal or equivocal MRI findings safely halved the number of prostate biopsies performed while maintaining equivalent detection of clinically significant prostate cancer, according to results from PRIMARY2 (NCT05154162), a multicenter, phase 3 randomized controlled trial presented at the 41st Annual Congress of the European Association of Urology in London, United Kingdom.¹

The trial enrolled 660 biopsy-naive men with clinical suspicion of significant prostate cancer (sPCa), PI-RADS 2 or 3 findings on multiparametric MRI, and at least one risk factor such as PSA density greater than 0.1 or strong family history. Participants were randomly assigned 1:1 to systematic transperineal biopsy or to pelvic PSMA PET-CT, with subsequent biopsy decisions guided by imaging results. Those with a positive PET scan (PRIMARY score 3–5) underwent targeted transperineal biopsy; those with a negative scan (PRIMARY score 1–2) proceeded to PSA monitoring without biopsy.

"We took 660 patients who had a normal or an equivocal MRI, but a persisting suspicion—a red flag—and we randomized them," said Declan Murphy, MB, BCH, BaO, FRACS, FRCS, Urol, a study investigator. "Half of the patients got what we presumed to be the standard of care, which is a systematic biopsy. The other half got a PET scan, and depending on the results of the PET scan, we either did not do a biopsy or we did a targeted biopsy."

The trial met both co-primary end points. In the PSMA PET-CT arm, biopsy was avoided in 163 of 331 participants (49%; 95% CI, 44–55%; P < .001). sPCa was diagnosed in 39 of 331 patients (12%) in the experimental arm compared with 51 of 329 (16%) in the control arm, meeting the prespecified non-inferiority margin (difference −3.7%; 95% CI, −8.9% to 1.5%; P = .009).

"If you follow a paradigm where in men with a normal or an equivocal MRI, but a bit of a red flag for clinical suspicion, you do a PET scan instead of just systematically biopsying the prostate—half the men avoid a biopsy," Murphy said. "And of those who have a biopsy, the pick-up rate for significant cancer is the same."

A key secondary end point further strengthened the case for the PSMA-guided approach. Detection of insignificant prostate cancer fell from 32% in the control arm to 14% in the experimental arm (difference −18%; 97.5% CI, −25% to −11%; P < .001).

"We dramatically reduced the pick-up rate of insignificant cancer," Murphy said. "We don't want to be finding these insignificant cancers, and that's unfortunately what happens if you've got normal or equivocal MRI scans and you do systematic biopsies."

Murphy noted that the findings build on the original PRIMARY trial, which established PSMA PET-CT as a tool with improved negative predictive value for sPCa compared to MRI alone, and argued that the results now support a formal shift in practice.

"PSMA PET-CT should be incorporated in the diagnostic pathway of patients with a PI-RADS 3 or high clinical-suspicion PI-RADS 2 MRI," he said.

REFERENCE

1. Buteau JP, Moon D, Fahey MT, et al. Impact of [68Ga]Ga-PSMA-11 PET/CT in the diagnosis of prostate cancer in men with equivocal or non-suspicious findings on multi-parametric MRI (PRIMARY2): a multi-centre, phase III, randomised trial. Presented at: 41st Annual Congress of the European Association of Urology. London, UK. March 13-16, 2026