Prostate Imaging Using MRI +/- Contrast Enhancement

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.

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.

Eligibility Criteria:
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