Recruitment begins for the PRIME Study Prostate Imaging using MRI +/- contrast Enhancement Dr. Veeru Kasivisvanathan University College London and UCLH PRIME Chief Investigator
Mr. Vinson Wai-Shun Chan University College London and University of Leeds PRIME Research Assistant
primestudy@ ucl.ac.uk Twitter: @veerukasi
Twitter: @VinsonChan
Ms. Aqua Asif University College London and University of Leicester PRIME Research Assistant
Mr. Arjun Nathan University College London and UCLH PRIME Academic Clinical Fellow
Country
Site
Principal Investigator
United Kingdom
University College London Hospital
Veeru Kasivisvanathan, Caroline Moore
Royal Free Hospital
Paras Singh
Addenbrooke’s Hospital
Tristan Barrett, Christof Kastner
Whittington Hospital
Maneesh Ghei
Denmark
Herlev Gentofte University Hospital
Lars Boesen
Finland
Helsinki University Hospital
Antti Rannikko
Germany
University Hospital Essen
Claudia Kesch, Boris Hadaschik
Martini-Klinik am UKE
Lars Budaeus
Heinrich Heine University Düsseldorf
Jan Philipp Radtke, Lars Schimmöller
University Hospital Frankfurt
Felix Chun, Felix Preisser
University Hospital Reina Sofía
Enrique Gómez Gómez, Daniel José López Ruiz
University Hospital La Moraleja
Miguel Angel Rodríguez Cabello, Carolina Aulló Gonzanlez
Mayo Clinic, Rochester
Lance A Mynderse
NYU Langone
Samir S. Taneja
Weill-Cornell Medical Center
Daniel Jason Aaron Margolis, Jim C Hu
Icahn School of Medicine, Mount Sinai
Ash Tewari
Sorbonne Université
Raphaele Renard Penna
Centre Hospitalier Universitaire de Bordeaux
Gregoire Robert
Spain United States of America
France
Twitter: @ArjunSNathan
Twitter: @AquaOishee Background Multiparametric MRI (mpMRI) is internationally recommended for men who present with suspicion of prostate cancer. This change in guidelines recommendation has created a new demand on resources.
full mpMRI. All MRI scans are reported using Likert and PI-RADS v2.1 scores.
Patients with non-suspicious MRI (scores 1 or 2) on bpMRI and mpMRI and low risk of PCa will be recommended to undergo PSA surveillance. Patients with suspicious MRI (scores 3,4 or 5) on either bpMRI We believe that every man who needs an MRI should or mpMRI will undergo MRI-targeted biopsy. have access to one. Suspicious areas will be labelled with their location and whether they were suspicious on either bpMRI or Would removing the dynamic contrast enhanced (DCE) mpMRI. Targeted biopsy cores will be stored images from mpMRI help in delivering our goal? separately from areas that were uniquely suspicious The DCE sequence can be time and labour consuming on DCE so that conclusions can be made on whether due to the use of intravenous contrast. Recent data the pathology was from suspicious areas on the has suggested that the DCE sequence may not be bpMRI or mpMRI or both. Systematic biopsies will necessary and the biparametric (T2W and DWI) also be taken. The simplified study schema is shown sequences may detect as much clinically significant below in Figure 1. prostate cancer (csPCa). Primary outcome: The proportion of men with Replacing the mpMRI scan with a bpMRI scan can clinically significant cancer detected (Gleason score ≥ increase the number of MRI scans performed in any 3+4) / Gleason Grade Group 2 or greater). given day, reduce costs from the need for medical staff to be present and reduce the need for use of Key secondary outcomes: contrast medium. This would make meeting the high 1) Agreement between bpMRI and mpMRI in score demand of MRI scans now required in prostate cancer of suspicion; diagnosis more feasible. 2) Proportion of men with clinically insignificant cancer detected (Gleason grade 3+3 / Gleason Limitations of some of the previous studies in this grade group 1) and; area: 3) Agreement between bpMRI and mpMRI on • Small sample size, single institution retrospective treatment decision eligibility studies • No true blinding of the radiologists reporting the Study recruitment and current status We are delighted to announce that the PRIME study bi-parametric MRI to the DCE sequence has attracted over 60 sites from 22 countries expressing • Using an MRI scoring system that already assumes that DCE has no role in differentiating interest to take part. Sites thereafter undergo quality control of their MRI facilities to assess their eligibility, between who needs a biopsy and who doesn’t using the Prostate Imaging Quality (PI-QUAL) scoring • No MRI-targeted biopsies system (1). The PI-QUAL scoring system was developed from the PRECISION study (2), and gives a score of 1-5 Aim for an MRI scan relating to its image quality. A score of The PRIME study, therefore, aims to assess whether 1 means no mpMRI sequences are of diagnostic quality, bi-parametric MRI (T2W & DWI) is non-inferior to a score of 3 means mpMRI quality was of sufficient multi-parametric MRI (T2W, DWI and DCE) in the diagnostic quality and a score of 5 means each diagnosis of clinically significant prostate cancer. sequence is independently of optimal diagnostic quality (1). Sites are helped to improve their MRI Sample size quality so that they can take part in the study. The full 500 patients site recruitment process is shown in Figure 2. Intended length of recruitment Current Status 24 months MRI quality control has occurred for 40 centres, with now 32 of them achieving an optimal PI-QUAL score Patient eligibility criteria of 5. Currently, there are 26 sites in the set-up stage. Key inclusion criteria: 1. Men at least 18 years of age referred with clinical The coordinating site, University College London suspicion of prostate cancer 2. Serum PSA ≤ 20ng/ml 3. Able to provide written informed consent
Centre Hospitalier Universitaire de Lille
Arnauld Villers, Philippe Puech
The Netherlands
Radboud University Medical Center
Maarten de Rooij, Bas Israël
Belgium
Ghent University Hospital
Pieter De Visschere
Italy
University Hospital of Udine
Rossano Girometti
University of Rome Tor Vergata
Roberto Miano
San Giovanni Battista Hospital
Marco Gatti, Giancarlo Marra
San Raffaele Hospital
Alberto Briganti
Sapienza University of Rome
Valeria Panebianco
Singapore
Tan Tock Seng Hospital
Jeffrey J Leow
Brazil
Hospital Sírio-Libanês
Publio Cesar Cavalcante Viana, Adriano Basso Dias
Argentina
Centre de Urologia CDU
Marcelo Borghi, Hernando Rios Pita
Canada
Princess Margaret Cancer Centre
Sangeet Ghai
Australia
Alfred Health, Monash University
Jeremy Grummet, Richard O'Sullivan
Peter MacCallum Centre Centre
Declan Murphy
Table 1: Sites undergoing contracting process and their principal investigators
Hospital (UCLH), is the first site to have completed the site initiation visit. Our team looks forward to opening more sites internationally throughout 2022. We anticipate recruitment to close by Q1 2024. Implications of study If bpMRI is non-inferior to mpMRI, then bpMRI will become the new standard of care for prostate cancer detection in men with suspected prostate cancer. This will allow a greater capacity to deliver MRI scans so that every man who needs a scan will be able to get one. If however, the DCE sequence in mpMRI identifies a large proportion of significant cancer and significantly influences staging and treatment eligibility decisions, then mpMRI will be recommended to stay the standard of care. Funding The PRIME Study (NCT04571840) is funded by Prostate Cancer UK, The John Black Charitable Foundation, the European Association of Urology Research Foundation, and the Dieckmann Foundation.
Chief Radiologists: Dr. Clare Allen, Dr. Francesco Giganti Chief Pathologists: Dr. Alex Freeman, Dr. Aiman Haider Health Economists: Prof. Laura Lorelle, Dr. Caroline Clarke, Miss Jessica Weng EAU Research Foundation: Dr. Wim Witjes, Ms. Christien Caris, Prof. Anders Bjartell, Ms. Joke Van Egmond Trial Network: PRECISION & START Consortium Study website https://www.ucl.ac.uk/surgery/research/departmenttargeted-intervention/urology/prime-trial-information References 1. Giganti F, Allen C, Emberton M, Moore CM, Kasivisvanathan V. Prostate Imaging Quality (PI-QUAL): A New Quality Control Scoring System for Multiparametric Magnetic Resonance Imaging of the Prostate from the PRECISION trial. Eur Urol Oncol. 2020;3(5):615-9. 2. Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, et al. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. New England Journal of Medicine. 2018;378(19):1767-77.
The Trial Management Group includes: Chief Investigator: Dr. Veeru Kasivisvanathan University College London NCITA Trials group: Prof. Caroline Moore, Dr. Pramit Khetrapal, Dr. Chris Brew-Graves, Dr. Nicola Muirhead, Ms. Réka Novota, Mr. Phil Ryan, Prof. Shonit Punwani, Prof. Mark Emberton, Mr. Alexander Ng, Ms. Aqua Asif, Mr. Vinson Wai-Shun Chan, Mr. Arjun Nathan, Ms. Marimo Rossiter Statistics by University of Birmingham Test Evaluation Research Group, Dr. Yemisi Takwoingi, Prof. Jon Deeks, Dr. Ridhi Agarwal.
Key exclusion criteria: 1. Prior prostate biopsy or prostate MRI 2. Contraindication to MRI or prostate biopsy Study design PRIME (NCT04571840) is a prospective, international, within-patient, multicentre, level 1–evidence clinical trial evaluating whether bpMRI is noninferior to mpMRI in the detection of csPCa. Men with clinical suspicion of PCa undergo mpMRI as per standard of care. The DCE sequence is then blinded from the radiologists to report the bpMRI. The DCE sequence will then be unblinded to the radiologist to report the EAU Research Foundation
March/May 2022
Fig. 1: Simplified study scheme
Fig. 2: Flow chart of the site approval process
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