EAU RF announces PRIME Study: Prostate imaging using MRI +/- contrast enhancement

We are looking for centres to take part in the PRIME Study. The study is brought to you by the team that delivered the PRECISION Study.

Background

Since the publication of PRECISION, MRI-FIRST, and a number of other high-profile studies, the EAU and other international guidelines panels now recommend performing multiparametric MRI in men when they first present with suspicion of prostate cancer. Meeting the new increased demand for MRI scans can be a challenge.

We aim to ensure that every man who needs an MRI has access to one. One method of achieving this is by streamlining the multiparametric MRI scan. There is uncertainty in whether the contrast sequences in the multiparametric MRI contribute significantly to the detection of clinically significant cancer and subsequent treatment decisions. The PIRADs committee have highlighted this as an important area of research.

Dynamic contrast enhanced images

A full multiparametric MRI (T2-weighted images (T2W), diffusion weighted images (DWI) and dynamic contrast enhanced images (DCE)) takes approximately 30 minutes. The DCE sequence takes around a third of this scan time. It requires a health practitioner to insert a cannula into the patient for gadolinium contrast administration and requires a doctor to be present in the event of contrast reaction. Recent data has raised questions over the long-term safety of the gadolinium contrast.

Removing the contrast sequence can increase the number of MRI scans performed in any given day, reduce costs (less medical staff need to be present) and reduce the need for use of contrast medium. This would make meeting the high demand of MRI scans now required in prostate cancer diagnosis much more feasible.

Aim

The PRIME study aims to assess whether biparametric MRI (T2W & DWI) is non-inferior to multi-parametric MRI (T2W, DWI and DCE) in the diagnosis of clinically significant prostate cancer.

Limitations of some of the previous studies in this area were:

• Small sample size, single institution retrospective studies
• No true blinding of the radiologists reporting the biparametric MRI to the DCE sequence
• Using an MRI scoring system that already assumes that DCE has no role in differentiating between who needs a biopsy and who does not
• No MRI-targeted biopsies

"We aim to ensure that every man who needs an MRI has access to one."

Sample size required

500 patients

Intended length of recruitment

24 months from recruitment of the first patient

Patient eligibility criteria

Key Inclusion criteria:

1. Men at least 18 years of age referred with clinical suspicion of prostate cancer
2. Serum PSA ≤ 20 ng/ml
3. Able to provide written informed consent

Key exclusion criteria:

1. Prior prostate biopsy or prostate MRI
2. Contraindication to MRI or prostate biopsy

Study design

PRIME is an international multi-centre prospective diagnostic test evaluation 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 for the radiologist who reports the biparametric (bpMRI) first. After reporting the bpMRI, the DCE sequence is made available to the radiologist who reports the multi-parametric (mpMRI). The MRIs and lesions are scored on a 1-5 scale 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)

Subsequent recommendations

Men with non-suspicious MRI on bpMRI and mpMRI and low risk of cancer will be recommended to undergo PSA surveillance. Suspicious areas scoring 3, 4 or 5 on either bpMRI or mpMRI will undergo MRI-targeted biopsy using the information from the bpMRI and mpMRI to influence biopsy conduct. Suspicious areas will be labelled with their location and whether they were suspicious on either bpMRI, mpMRI, or both sequences. Targeted biopsy cores will be stored separately from areas that were uniquely suspicious on DCE so that conclusions can be made on whether the pathology was from suspicious areas on the bpMRI or mpMRI.

In addition, systematic biopsies will be taken. 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 has on the treatment decision will also be evaluated.

Figure 1: Simplified study scheme

Primary outcome

The primary outcome is the proportion of men with clinically significant cancer detected (Gleason Grade ≥ 3+4) / Gleason grade group 2 or greater).

Key secondary outcomes:

1. Agreement between bpMRI and mpMRI in score of suspicion
2. Proportion of men with clinically insignificant cancer detected (Gleason grade 3+3 / Gleason grade group 1)
3. Proportion of men with significant cancer missed by bpMRI & mpMRI-targeted biopsies and detected by systematic biopsy

MRI requirements:High-quality MRI

Biopsy requirements:Either visually targeted or software-assisted fusion targeted biopsies are permitted. Transperineal biopsy approach is the ideal standard.

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 suspicious MRIs. 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 as the standard of care.

Funding

Veeru Kasivisvanathan is funded by a National Institute for Health Research Academic Clinical Lectureship. The PRIME study has been supported by an EAU Research Foundation Grant.

Participating sites will be paid for participation with per patient recruited payments.

Requirements for your centre to take part:

1. Prompt communication and prompt completion of study eligibility forms
2. Good quality MRI imaging and experience in MRI-targeted biopsy
3. Either publications showing your detection rates of clinically significant prostate cancer by MRI-targeted biopsy or provide audit data for your detection rates from your last 100 MRI-targeted biopsies
4. Willingness to work with the UCL team in advance of the study to optimise your imaging protocols before taking part in PRIME
5. Be able to obtain all local approvals and start recruiting patients within 6 months
6. Aim for recruitment of at least 50 patients in 12 months (4-5 patients per month)
7. Give the names of a dedicated named radiologist, urologist, and data entry contact responsible for successful delivery of the study at your site and copy them in the email expressing your interest (see next paragraph)

If your centre meets these requirements and you are interested in taking part in PRIME, please email veeru.kasi@ucl.ac.uk, copy and paste the above requirements with specific confirmation that you can meet each one and answers to the above points where applicable.

The Trial Management Group includes

Chief Investigator: Dr. V. KasivisvanathanUCL NCITA Trials Group: Dr. C. Brew-Graves, Prof. S. Punwani, Prof. C. Moore, Dr. P. KhetrapalStatistics by University of Birmingham Test Evaluation Research Group, Dr. Y. Takwoingi, Prof. J. DeeksEAU Research Foundation: Dr. W. Witjes, Ms. C. Caris, Prof. A. BjartellTrial Network: PRECISION & START Consortium