PRIMARY2: A phase III, multi-centre, randomised controlled trial investigating the additive diagnostic value of [68Ga]Ga-PSMA-11 PET/CT in men with negative/equivocal MRI in the diagnosis of clinically significant prostate cancer

TPS397 Background: Multi-parametric magnetic resonance imaging (MRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa), with superior diagnostic accuracy compared with transrectal ultrasound guided prostate biopsy alone. PRIMARY demonstrated significant improvement in sensitivity (97% vs 83%) and negative predictive value (91% vs 72%) with the addition of [68Ga]Ga-PSMA-11 PET/CT (PSMA PET/CT) vs MRI alone. Furthermore, 38% of patients with PI-RADS 2 or 3 were true negative on PSMA PET/CT, a population which may potentially benefit from avoiding transperineal prostate biopsy (TPPB). We hypothesize that the addition of PSMA PET/CT is non-inferior to MRI for the detection of sPCa in men with PI-RADS 2-3 disease, while providing the advantages of reducing unnecessary biopsies and limiting to targeted-only TPPB. Methods: This multi-centre, two-arm, randomized controlled, phase III trial will recruit 660 men with high clinical suspicion of sPC. Participants will be randomized in a 1:1 ratio in permuted blocks, stratified by center. In the experimental arm, participants will undergo a pelvic PSMA PET/CT. Local and central reviewers will interpret independently, based on the PRIMARY Score. Participants with a positive result will undergo targeted-TPPB, whereas those with negative PSMA PET/CT will avoid biopsy. In the control arm, all participants undergo template-TPPB. Patients will continue follow-up for subsequent clinical care for up to two years post-randomization. Key eligibility criteria include an MRI result of PI-RADS 2 with at least one red flag [PSA density >0.1, abnormal digital rectal examination (DRE), strong family history, BRCA mutation, PSA >10, PSA doubling time 0.75/year], or PI-RADS 3, having never undergone a prostate biopsy