PRIME: Prostate Imaging Using MRI +/- Contrast Enhancement

Sponsor

University College, London (Other)

Overall Status

Recruiting

CT.gov ID

NCT04571840

Collaborator

(none)

500

Enrollment

Locations

Arms

22.9

Anticipated Duration (Months)

16.1

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Diagnostic Test: Multiparametric MRI +/- prostate biopsy Diagnostic Test: Biparametric MRI +/- prostate biopsy	N/A

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:

- Very low (clinically significant cancer is highly unlikely to be present)
- Low (clinically significant cancer is unlikely to be present)
- Intermediate (the presence of clinically significant cancer is equivocal)
- High (clinically significant cancer is likely to be present)
- 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

Within-person controlled, paired cohort, diagnostic evaluation study. Participants undergo two index tests and a reference test.Within-person controlled, paired cohort, diagnostic evaluation study. Participants undergo two index tests and a reference test.

Masking:

Single (Care Provider)

Masking Description:

Radiologist assessing MRI for suspicion of prostate cancer is blinded to the contrast sequence when reporting the biparametric MRI. After this report, they are unblinded to the contrast sequence and report the multiparametric MRI. All biopsies conducted as a result of MRI findings will be labelled as bpMRI and mpMRI, and diagnostic accuracy will be assessed against histology findings.

Primary Purpose:

Diagnostic

Official Title:

A Study Comparing Bi-parametric MRI to Multi-parametric MRI in the Diagnosis of Clinically Significant Prostate Cancer

Actual Study Start Date :

Apr 5, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: mpMRI Multiparametric MRI	Diagnostic Test: Multiparametric MRI +/- prostate biopsy MRI with T2-weighted, diffusion weighted and dynamic contrast enhanced sequences followed by prostate biopsy if indicated on MRI and clinical findings
Experimental: bpMRI Biparametric MRI	Diagnostic Test: Biparametric MRI +/- prostate biopsy MRI with T2-weighted and diffusion weighted sequences followed by prostate biopsy if indicated on MRI and clinical findings

Arm

Intervention/Treatment

Active Comparator: mpMRI

Multiparametric MRI

Diagnostic Test: Multiparametric MRI +/- prostate biopsy

MRI with T2-weighted, diffusion weighted and dynamic contrast enhanced sequences followed by prostate biopsy if indicated on MRI and clinical findings

Experimental: bpMRI

Biparametric MRI

Diagnostic Test: Biparametric MRI +/- prostate biopsy

MRI with T2-weighted and diffusion weighted sequences followed by prostate biopsy if indicated on MRI and clinical findings

Outcome Measures

Primary Outcome Measures

Proportion of men with clinically significant cancer [When biopsy results available, at an expected average of 30 days post-biopsy]

Secondary Outcome Measures

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 score of suspicion [When 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.
Agreement between bpMRI and mpMRI for radiological staging decision [When MRI results available, at an expected average of 30 days post-MRI]
Agreement between bpMRI and mpMRI for treatment eligibility [When 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.
Test performance characteristics for bpMRI & mpMRI when using the Likert scoring system in comparison to the PIRADS scoring system [When biopsy results available, at an expected average of 30 days post-MRI]
Proportion of men with cancer missed by bpMRI and mpMRI-targeted biopsies and detected by systematic biopsy [When biopsy results available, at an expected average of 30 days post-biopsy]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Men at least 18 years of age referred with clinical suspicion of prostate cancer
Serum PSA ≤ 20ng/ml
Fit to undergo all procedures listed in protocol
Able to provide written informed consent

Exclusion Criteria:

Prior prostate biopsy
Prior treatment for prostate cancer
Prior prostate MRI on a previous encounter
Contraindication to MRI
Contraindication to prostate biopsy
Unfit to undergo any procedures listed in protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905
2	NYU Langone	New York	New York	United States	10016
3	Icahn School of Medicine (Mount Sinai)	New York	New York	United States	10029
4	New York Presbyterian Hospital	New York	New York	United States	10032
5	Centro de Urologia	Buenos Aires		Argentina
6	Peter MacCallum Cancer Centre	Melbourne E.		Australia
7	Monash University	Melbourne		Australia
8	Ghent University Hospital	Ghent		Belgium
9	Hospital Sírio-Libanês	São Paulo		Brazil
10	Princess Margaret Cancer Centre	Toronto		Canada
11	Herlev and Gentofte Hospital	Copenhagen		Denmark
12	Helsinki University Hospital	Helsinki		Finland
13	Bordeaux Pellegrin University Hospital	Bordeaux		France
14	CHU Lille	Lille		France
15	Sorbonne Université	Paris		France
16	Heinrich Heine University Düsseldorf	Düsseldorf		Germany
17	Essen University Hospital	Essen		Germany
18	University Hospital Frankfurt	Frankfurt		Germany
19	Martini Klinik	Hamburg		Germany
20	San Raffaele Hospital	Milan		Italy
21	Sapienza University	Rome		Italy
22	San Giovanni Battista Hospital	Turin		Italy
23	University Hospital of Udine	Udine		Italy
24	Radboudumc	Nijmegen		Netherlands
25	Tan Tock Seng Hospital	Novena		Singapore
26	Hospital Universitario Reina Sofía	Córdoba		Spain
27	Hospital Universitario La Moraleja	Madrid		Spain
28	Addenbrooke's Hospital	Cambridge		United Kingdom
29	Royal Free London NHS Foundation Trust	London		United Kingdom
30	University College London and University College London Hospital	London		United Kingdom
31	Whittington Hospital	London		United Kingdom