Protocol for the PRIMARY clinical trial, a prospective, multicentre, cross-sectional study of the additive diagnostic value of gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer

Amer Amin^{1

2

3

4}, Alexandar Blazevski^{1

2

3

4}, James Thompson^{2

3

5}, Matthijs J Scheltema^{2

3

6}, Michael S Hofman^{7

8}, Declan Murphy^{8

9}, Nathan Lawrentschuk^{8

9

10

11}, Niranjan Sathianathen⁹, Jada Kapoor⁹, Henry H Woo^{12

13}, Venu Chalasani¹⁴, Krishan Rasiah^{3

15}, Pim J van Leeuwen¹⁶, Reuben Tang¹, Thomas Cusick³, Phillip Stricker^{2

3

4}, Louise Emmett^{1

3

4}

Affiliations

¹ Department of Theranostics and Nuclear Medicine, St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia.
² St Vincent's Prostate Cancer Centre, Darlinghurst, NSW, Australia.
³ Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
⁴ St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.
⁵ St George Clinical School, University of New South Wales, Sydney, NSW, Australia.
⁶ Department of Urology, UMC, Amsterdam, The Netherlands.
⁷ Centre for Molecular Imaging, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.
⁸ Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Vic., Australia.
⁹ Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.
¹⁰ Department of Surgery, Austin Health, The University of Melbourne, Parkville, Vic., Australia.
¹¹ Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, Vic., Australia.
¹² Sydney Adventist Hospital Clinical School, University of Sydney, Wahroonga, NSW, Australia.
¹³ Department of Uro-Oncology, Chris O'Brien Lifehouse, Sydney, NSW, Australia.
¹⁴ University of Sydney, Sydney, NSW, Australia.
¹⁵ Department of Urology, Royal North Shore Private Hospital, St Leonards, NSW, Australia.
¹⁶ Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

PMID: 31957122
DOI: 10.1111/bju.14999

Protocol for the PRIMARY clinical trial, a prospective, multicentre, cross-sectional study of the additive diagnostic value of gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer

Amer Amin et al. BJU Int. 2020 Apr.

. 2020 Apr;125(4):515-524.

doi: 10.1111/bju.14999. Epub 2020 Feb 12.

Authors

Affiliations

¹ Department of Theranostics and Nuclear Medicine, St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia.
² St Vincent's Prostate Cancer Centre, Darlinghurst, NSW, Australia.
³ Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
⁴ St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.
⁵ St George Clinical School, University of New South Wales, Sydney, NSW, Australia.
⁶ Department of Urology, UMC, Amsterdam, The Netherlands.
⁷ Centre for Molecular Imaging, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.
⁸ Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Vic., Australia.
⁹ Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.
¹⁰ Department of Surgery, Austin Health, The University of Melbourne, Parkville, Vic., Australia.
¹¹ Olivia Newton-John Cancer and Wellness Centre, Austin Health, Heidelberg, Vic., Australia.
¹² Sydney Adventist Hospital Clinical School, University of Sydney, Wahroonga, NSW, Australia.
¹³ Department of Uro-Oncology, Chris O'Brien Lifehouse, Sydney, NSW, Australia.
¹⁴ University of Sydney, Sydney, NSW, Australia.
¹⁵ Department of Urology, Royal North Shore Private Hospital, St Leonards, NSW, Australia.
¹⁶ Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

PMID: 31957122
DOI: 10.1111/bju.14999

Abstract

Objectives: Primary objectives: To determine the additive value of gallium-68 prostate-specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI-RADS ≥3) but negative PSMA-PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA-PET/CT or only by systematic prostate biopsy; to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA-PET/CT; to assess whether there may be health economic benefit or harm if PSMA-PET/CT is incorporated into the diagnostic algorithm; and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa.

Patients and methods: The PRIMARY trial is a multicentre, prospective, cross-sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic-only) PSMA-PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA-PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA-PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA-PET/CT will be blinded to each other.

Results: The PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA-PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA-PET/CT into the diagnostic algorithm.

Conclusions: This trial will provide robust prospective data to determine the diagnostic ability of PSMA-PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa.

Keywords: PSMA; PSMA-PET scan; clinically significant prostate cancer; multiparametric MRI; prostate cancer.

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References

1. Loeb S, Vellekoop A, Ahmed HU et al. Systematic review of complications of prostate biopsy. Eur Urol 2013; 64: 876-92
1. Corcoran NM, Hovens CM, Hong MKH et al. Underestimation of Gleason score at prostate biopsy reflects sampling error in lower volume tumours. BJU Int 2012; 109: 660-4
1. Woo S, Suh CH, Kim SY, Cho JY, Kim SH. Diagnostic performance of prostate imaging reporting and data system version 2 for detection of prostate cancer: a systematic review and diagnostic meta-analysis. Eur Urol 2017; 72: 177-88
1. Thompson JE, van Leeuwen PJ, Moses D et al. The diagnostic performance of multiparametric magnetic resonance imaging to detect significant prostate cancer. The J Urol 2016; 195: 1428-35
1. Thompson JE, Moses D, Shnier R et al. Multiparametric magnetic resonance imaging guided diagnostic biopsy detects significant prostate cancer and could reduce unnecessary biopsies and over detection: a prospective study. J Urol 2014; 192: 67-74

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