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.

Abstract

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 <36 months, PSA velocity >0.75/year], or PI-RADS 3, having never undergone a prostate biopsy, <cT3 on DRE, and PSA ≤20 ng/mL. The co-primary objectives are to estimate the percentage difference in sPCa between the experimental and control arms, and the percentage of participants who avoid TPPB in the experimental arm. The primary endpoints will be analyzed on the intention-to-treat principle. The main secondary objectives are the percentage difference between arms in insignificant prostate cancer, in complications following biopsy, in health-related quality of life, generalized anxiety, cancer worry, as well as the health economics impact. Patient enrolment began in March 2022, with recruitment expected to take 36 months. Clinical trial information: NCT05154162 .

Beyond Prostate Imaging Reporting and Data System: Combining Magnetic Resonance Imaging Prostate Imaging Reporting and Data System and Prostate-Specific Membrane Antigen–Positron Emission Tomography/Computed Tomography PRIMARY Score in a Composite (P) Score for More Accurate Diagnosis of Clinically Significant Prostate Cancer

“…3 This hypothesis is being tested in the phase 3 randomized PRIMARY2 trial, where patients with PIRADS 2/3 are randomized to standard of care or a PSMA-guided approach (PSMA negative—no biopsy, PSMA positive—targeted biopsy only; NCT05154162). 12 Cost effectiveness is an important component of the PRIMARY2 trial and will be integral to any broader use of PSMA-PET prior to prostate diagnosis.…”

The Current Landscape of Prostate-Specific Membrane Antigen (PSMA) Imaging Biomarkers for Aggressive Prostate Cancer

“…An ongoing multicentre, two-arm, randomised controlled Phase III trial currently recruiting patients, the PRIMARY 2 trial (NCT05154162), will test the additive value of PSMA PET/CT for PCa diagnoses in men with negative or equivocal MRI [ 41 ]. The authors hypothesise that the trial findings may provide the advantage of reducing unnecessary biopsies in patients with PIRADS 2–3 [ 41 ].…”

Key learnings from concordant systematic biopsies in prostate‐specific membrane antigen positron emission tomography/computed tomography‐guided prostate biopsies: Enhancing targeting accuracy

“…Given the emerging role of 68Ga-Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) in prostate cancer (PCa), strategies for its use in primary diagnosis are currently under investigation. [1][2][3] An advantage of PSMA-PET/CT is its ability to provide complete disease staging as well as an assessment of the local tumor extent in the prostate. 4 In Addition, PSMA-PET/CT is equivalent to magnetic resonance imaging (MRI) in reliably identifying the most aggressive tumor site, 5,6 thus qualifying it for planning local and focal therapies.…”

“…Given the emerging role of 68Ga‐Prostate‐specific membrane antigen positron emission tomography/computed tomography (PSMA‐PET/CT) in prostate cancer (PCa), strategies for its use in primary diagnosis are currently under investigation 1‐3 . An advantage of PSMA‐PET/CT is its ability to provide complete disease staging as well as an assessment of the local tumor extent in the prostate 4 .…”