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Prostate Imaging Using MRI +/- Contrast Enhancement

Not Applicable
Conditions
Prostate Cancer
Interventions
Diagnostic Test: Multiparametric MRI +/- prostate biopsy
Diagnostic Test: Biparametric MRI +/- prostate biopsy
Registration Number
NCT04571840
Lead Sponsor
University College, London
Brief Summary

This prospective clinical trial (PRostate Imaging using Mri +/- contrast Enhancement (PRIME)) aims to assess whether biparametric MRI (bpMRI) is non-inferior to multiparametric mpMRI (mpMRI) in the detection of clinically significant prostate cancer.

This means that we are comparing MRI scans that requires injection of IV contrast (the current standard practice) versus MRI scans that can be performed without IV contrast in the detection of prostate cancer.

Detailed Description

The PRECISION study (NCT02380027) has established that multiparametric MRI +/- targeted biopsy of suspicious areas identified on MRI is superior to standard 12 core TRUS biopsy in the detection of clinically significant prostate cancer (Gleason \> 3+ 4) (38% vs 26%), in reducing the detection of clinically insignificant prostate cancer (Gleason 3 + 3) (9% vs 22%) and in maximising the proportion of cores positive for prostate cancer (44% vs 19%).

Multiparametric MRI (mpMRI) typically uses T2-weighted (T2W), diffusion-weighted (DWI) and dynamic contrast enhanced (DCE) sequences. As a mpMRI is a precious resource, due to capacity and resource limitations, one of the major challenges across institutions is delivering a health service with pre-biopsy MRI before a biopsy in all men with suspected prostate cancer.

However, biparametric MRI (bpMRI), that is, a combination of T2W and DWI, which does not use the DCE sequences, has demonstrated similar detection rates of prostate cancer as mpMRI in some studies and there is a debate about the necessity of the DCE sequence.

The potential advantages of avoiding the DCE sequence include avoiding the cost associated with it, shorter scan time, avoiding the need for medical practitioner attendance, and avoiding putative basal ganglia accumulation and the possibility of adverse neurological effect. Thus, a bpMRI approach may be more feasible and have health-economic benefits over a mpMRI approach and may thus increase the accessibility of this resource to men who need it.

PRIME is a multi-centre study. Men referred with clinical suspicion of prostate cancer based on raised prostate specific antigen (PSA) or abnormal digital rectal examination (DRE) who have had no prior biopsy undergo mpMRI. The DCE sequence is blinded from the radiologist who reports the bpMRI first. After reporting the bpMRI, the DCE sequence is made available to the radiologist who reports the mpMRI. The MRIs and lesions are scored on 1-5 scales of suspicion for the likelihood that clinically significant cancer is present:

1. - Very low (clinically significant cancer is highly unlikely to be present)

2. - Low (clinically significant cancer is unlikely to be present)

3. - Intermediate (the presence of clinically significant cancer is equivocal)

4. - High (clinically significant cancer is likely to be present)

5. - Very high (clinically significant cancer is highly likely to be present)

Men with non-suspicious MRI on bpMRI and mpMRI and low clinical risk of prostate cancer will be counselled by their clinical teams as per routine clinical care. In routine clinical practice these men typically do not undergo prostate biopsy.

Suspicious areas scoring 3, 4 or 5 on either bpMRI or mpMRI will undergo targeted and systematic biopsy using the information from the mpMRI to influence biopsy conduct. Suspicious areas will be labelled by their MRI score, with their location according to sector diagrams.

The proportion of patients with clinically significant prostate cancer will be ascertained and compared between bpMRI and mpMRI.

Treatment eligibility decisions without the DCE information will be made and once the clinicians are unblinded to the DCE sequence the impact that this information makes on the treatment decision will be evaluated.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Male
Target Recruitment
500
Inclusion Criteria
  1. Men at least 18 years of age referred with clinical suspicion of prostate cancer
  2. Serum PSA ≤ 20ng/ml
  3. Fit to undergo all procedures listed in protocol
  4. Able to provide written informed consent
Exclusion Criteria
  1. Prior prostate biopsy
  2. Prior treatment for prostate cancer
  3. Prior prostate MRI on a previous encounter
  4. Contraindication to MRI
  5. Contraindication to prostate biopsy
  6. Unfit to undergo any procedures listed in protocol

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
mpMRIMultiparametric MRI +/- prostate biopsyMultiparametric MRI
bpMRIBiparametric MRI +/- prostate biopsyBiparametric MRI
Primary Outcome Measures
NameTimeMethod
Proportion of men with clinically significant cancerWhen biopsy results available, at an expected average of 30 days post-biopsy
Secondary Outcome Measures
NameTimeMethod
Agreement between bpMRI and mpMRI for radiological staging decisionWhen MRI results available, at an expected average of 30 days post-MRI
Cost-effectiveness of BpMRI compared to mpMRI (cost per diagnosis of prostate cancer)At an expected average of 30 days post-intervention

A within-trial analysis will be conducted to calculate the total cost for bpMRI and mpMRI and mean cost per patient if a strategy of bpMRI or mpMRI were adopted. The cost per diagnosis of clinically significant cancer will be calculated for bpMRI and mpMRI. An incremental cost effectiveness ratio may be calculated by deriving the additional cost per case of clinically significant cancer diagnosed. The cost of avoiding each additional case of clinically insignificant cancer diagnosed may also be calculated. Consideration will be given to extending this analysis using economic modelling to allow a lifetime perspective to be taken and the estimation of quality adjusted life years (QALYs). Costs of procedures will be estimated by multiplying standard unit costs by key resource using data captured within the trial. If possible, standard unit costs (e.g. NHS Reference costs) will be supplemented by unit cost data (and uncertainty around these costs) from the participating trial sites.

Agreement between bpMRI and mpMRI for score of suspicionWhen MRI results available, at an expected average of 30 days post-MRI

Score of suspicion on MRI (1-5) - lowest score = 1 = highly unlikely to be significant cancer. Highest score = 5 = highly likely to be significant cancer. For MRI to be non-suspicious it needs to be scored 1 or 2 on both Likert and PIRADSv2.1 systems. For MRI to be suspicious it can to be scored 3, 4 or 5 on either Likert or PIRADSv2.1 systems.

Test performance characteristics for bpMRI & mpMRI when using the Likert scoring system in comparison to the PIRADS scoring systemWhen biopsy results available, at an expected average of 30 days post-MRI
Proportion of men with clinically insignificant cancer (Gleason grade 3+3 / Gleason grade group 1)When biopsy results available, at an expected average of 30 days post-biopsy
Agreement between bpMRI and mpMRI for treatment eligibilityWhen treatment options discussed in multidisciplinary meeting, at an expected average of 30 days post intervention

At the coordinating centre, in a multi-disciplinary team meeting, treatment eligibility decisions without the DCE information will be made and once the clinicians are unblinded to the DCE sequence the impact that this information makes on the treatment decision will be evaluated.

Proportion of men with cancer missed by bpMRI and mpMRI-targeted biopsies and detected by systematic biopsyWhen biopsy results available, at an expected average of 30 days post-biopsy

Trial Locations

Locations (31)

Sapienza University

🇮🇹

Rome, Italy

San Giovanni Battista Hospital

🇮🇹

Turin, Italy

University Hospital of Udine

🇮🇹

Udine, Italy

Radboudumc

🇳🇱

Nijmegen, Netherlands

Tan Tock Seng Hospital

🇸🇬

Novena, Singapore

Hospital Universitario Reina Sofía

🇪🇸

Córdoba, Spain

Hospital Universitario La Moraleja

🇪🇸

Madrid, Spain

Addenbrooke's Hospital

🇬🇧

Cambridge, United Kingdom

Royal Free London NHS Foundation Trust

🇬🇧

London, United Kingdom

University College London and University College London Hospital

🇬🇧

London, United Kingdom

Whittington Hospital

🇬🇧

London, United Kingdom

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

NYU Langone

🇺🇸

New York, New York, United States

Icahn School of Medicine (Mount Sinai)

🇺🇸

New York, New York, United States

New York Presbyterian Hospital

🇺🇸

New York, New York, United States

Centro de Urologia

🇦🇷

Buenos Aires, Argentina

Peter MacCallum Cancer Centre

🇦🇺

Melbourne E., Australia

Monash University

🇦🇺

Melbourne, Australia

Ghent University Hospital

🇧🇪

Ghent, Belgium

Hospital Sírio-Libanês

🇧🇷

São Paulo, Brazil

Princess Margaret Cancer Centre

🇨🇦

Toronto, Canada

Herlev and Gentofte Hospital

🇩🇰

Copenhagen, Denmark

Helsinki University Hospital

🇫🇮

Helsinki, Finland

Bordeaux Pellegrin University Hospital

🇫🇷

Bordeaux, France

CHU Lille

🇫🇷

Lille, France

Sorbonne Université

🇫🇷

Paris, France

Heinrich Heine University Düsseldorf

🇩🇪

Düsseldorf, Germany

Essen University Hospital

🇩🇪

Essen, Germany

University Hospital Frankfurt

🇩🇪

Frankfurt, Germany

Martini Klinik

🇩🇪

Hamburg, Germany

San Raffaele Hospital

🇮🇹

Milan, Italy

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