Clinical Trial Protocol for PRIMARY2: A Multicentre, Phase 3, Randomised Controlled Trial Investigating the Additive Diagnostic Value of [68Ga]Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Negative or Equivocal Multiparametric Magnetic Resonance Imaging for the Diagnosis of Clinically Significant Prostate Cancer

James P Buteau; Daniel Moon; Michael T Fahey; Matthew J Roberts; James Thompson; Declan G Murphy; Nathan Papa; Catherine Mitchell; Richard De Abreu Lourenco; Haryana M Dhillon; Veeru Kasivisvanathan; Roslyn J Francis; Phillip Stricker; Shihka Agrawal; Jonathan O'Brien; Aoife McVey; Gaurav Sharma; Sidney Levy; Narjess Ayati; Andrew Nguyen; Su-Faye Lee; David A Pattison; Dinesh Sivaratnam; Mark Frydenberg; Yang Du; Jehan Titus; Sze-Ting Lee; Joseph Ischia; Greg Jack; Michael S Hofman; Louise Emmett

doi:10.1016/j.euo.2023.11.008

Clinical Trial Protocol for PRIMARY2: A Multicentre, Phase 3, Randomised Controlled Trial Investigating the Additive Diagnostic Value of [⁶⁸Ga]Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Negative or Equivocal Multiparametric Magnetic Resonance Imaging for the Diagnosis of Clinically Significant Prostate Cancer

Eur Urol Oncol. 2023 Dec 6:S2588-9311(23)00253-5. doi: 10.1016/j.euo.2023.11.008. Online ahead of print.

Authors

James P Buteau¹, Daniel Moon², Michael T Fahey³, Matthew J Roberts⁴, James Thompson⁵, Declan G Murphy⁶, Nathan Papa⁷, Catherine Mitchell⁸, Richard De Abreu Lourenco⁹, Haryana M Dhillon¹⁰, Veeru Kasivisvanathan¹¹, Roslyn J Francis¹², Phillip Stricker¹³, Shihka Agrawal¹⁴, Jonathan O'Brien⁶, Aoife McVey⁶, Gaurav Sharma¹⁵, Sidney Levy¹⁶, Narjess Ayati¹⁴, Andrew Nguyen¹⁴, Su-Faye Lee¹⁵, David A Pattison¹⁷, Dinesh Sivaratnam¹⁸, Mark Frydenberg¹⁹, Yang Du²⁰, Jehan Titus²¹, Sze-Ting Lee²², Joseph Ischia²³, Greg Jack²³, Michael S Hofman²⁴, Louise Emmett¹⁴

Affiliations

¹ Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia. Electronic address: jamespatrick.buteau@unimelb.edu.au.
² Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; Royal Melbourne Clinical School, University of Melbourne, Melbourne, Australia.
³ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁴ Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, Australia; UQ Centre for Clinical Research, Faculty of Medicine, University of Queensland, Brisbane, Australia.
⁵ Department of Urology, St. George Hospital, Sydney, Australia.
⁶ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁷ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
⁸ Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁹ Centre for Health Economics Research and Evaluation, University of Technology Sydney, Sydney, Australia.
¹⁰ Psycho-Oncology Cooperative Research Group, Centre for Medical Psychology & Evidence-based Decision-making, University of Sydney, Camperdown, Australia.
¹¹ Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; Division of Surgery and Interventional Science, University College London, London, UK.
¹² Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia; Medical School, University of Western Australia, Perth, Australia.
¹³ St. Vincent's Prostate Cancer Research Centre, Garvan Institute, UNSW Sydney, Sydney, Australia; Department of Urology, St. Vincent's Hospital, Sydney, Australia.
¹⁴ Department of Theranostics and Nuclear Medicine, St. Vincent's Hospital, Sydney, Australia; Faculty of Medicine, UNSW Sydney, Sydney, Australia.
¹⁵ Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Australia.
¹⁶ Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Department of Nuclear Medicine, Royal Melbourne Hospital, Melbourne, Australia; Department of Nuclear Medicine, Cabrini Health, Melbourne, Australia.
¹⁷ Department of Nuclear Medicine and Specialised PET Services, Royal Brisbane and Women's Hospital, Brisbane, Australia; School of Medicine, University of Queensland, Brisbane, Australia.
¹⁸ Department of Nuclear Medicine, Royal Melbourne Hospital, Melbourne, Australia; Department of Nuclear Medicine, Cabrini Health, Melbourne, Australia.
¹⁹ Department of Surgery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia; Cabrini Research, Cabrini Health, Melbourne, Australia.
²⁰ Department of Nuclear Medicine, PET and Bone Densitometry, South Australia Medical Imaging, Royal Adelaide Hospital, Adelaide, Australia.
²¹ Department of Urology, Royal Adelaide Hospital, Adelaide, Australia.
²² Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Australia.
²³ University of Melbourne Department of Surgery, Austin Health, Melbourne, Australia.
²⁴ Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.

PMID: 38061976
DOI: 10.1016/j.euo.2023.11.008

Abstract

Background: Multiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [⁶⁸Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection.

Objective: To demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites.

Design, setting, and participants: This multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162.

Intervention: In the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation.

Outcome measurements and statistical analysis: sPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis.

Conclusions: Patient enrolment began in March 2022, with recruitment expected to take 36 mo.

Patient summary: For patients with suspected prostate cancer who have nonsuspicious or unclear MRI (magnetic resonance imaging) scan findings, a different type of scan (called PSMA PET/CT; prostate-specific membrane antigen positron emission tomography/computed tomography) may identify men who could avoid an invasive prostate biopsy. This type of scan could also help urologists in better targeting of samples from suspicious lesions during prostate biopsies.

Keywords: Clinically significant prostate cancer; Diagnosis; Multiparametric magnetic resonance imaging; Positron emission tomography scan; Prostate cancer; Prostate-specific membrane antigen.

Associated data

ClinicalTrials.gov/NCT05154162