• No results found

The index test: multiparametric magnetic resonance imaging

In PROMIS, mpMRI was standardised to the minimal requirements advised by a European consensus meeting,66the European Society of Urogenital Radiology67and the British Society of Urogenital Radiology

guidelines.68T1-weighted, T2-weighted, diffusion-weighted [apparent diffusion coefficient (ADC) maps

and long-b scan] and dynamic gadolinium contrast-enhanced imaging was acquired using a 1.5-T scanner and a pelvic phased array (Table 3).

Endorectal coils were not used as there is no consensus on their role in minimal scanning requirements.66

Magnetic resonance spectroscopy was not included because evidence from a large prospective multicentre study at the time showed no benefit of spectroscopy for localisation of prostate cancer compared with T2-weighted imaging alone.69We decided to use only 1.5-T scanners as these were more widely available

in the UK health-care setting and most studies in the literature had reported the accuracy of mpMRI results based on 1.5-T scanners alone.

Quality assurance and reporting

A robust quality control process was used to maintain the quality of scans and ensure uniformity across all centres. All MRI scanners and individual mpMRI scans underwent quality control checks by an independent commercial imaging clinical research organisation appointed through open tender (IXICO plc, London, UK). Prior to site initiation, the lead radiologist (Alexander Kirkham) reviewed a number of prostate MRI scans from each centre and gave iterative feedback on improving scan quality.

BOX 1 Inclusion and exclusion criteria

Inclusion criteria

l Men aged≥18 years who are at risk of prostate cancer and have been advised to have a prostate biopsy.

l Serum PSA level of≤15 ng/ml within the previous 3 months.

l Suspected stage≤T2 on rectal examination (organ confined).

l Fit for general/spinal anaesthesia.

l Fit to undergo all protocol procedures including a TRUS-guided biopsy.

l Signed informed consent.

Exclusion criteria

l Treated using 5-alpha-reductase inhibitors at time of registration or during the prior 6 months.

l Previous history of prostate biopsy, prostate surgery or treatment for prostate cancer (interventions for benign prostatic hyperplasia/bladder outflow obstruction are acceptable).

l Evidence of a urinary tract infection or history of acute prostatitis within the last 3 months.

l Contraindication to MRI (e.g. claustrophobia, a pacemaker, an estimated glomerular filtration rate of ≤50 ml/minute).

l Any other medical condition precluding procedures described in the protocol.

l Contraindications for MRI (history of hip replacement surgery, metallic hip replacement or extensive pelvic orthopaedic metal work).

Reproduced from El-Shater Bosailyet al.16© 2015 The Authors. Published by Elsevier Inc. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

During the study, scans deemed to be of insufficient quality were repeated prior to biopsy. In addition, a standardised operating procedure for mpMRI reporting was adopted in line with the recommendations of the European consensus meeting66and the European Society of Urogenital-Radiology prostate MRI

guidelines.67This was convened before publication of the more recent Prostate Imaging Reporting and

Data System (PI-RADS) mpMRI reporting consensus.67Subsequent comparisons of the Likert and PI-RADS

reporting schemes have yielded similar results.70,71

At each centre, mpMRI scans were reported by dedicated urological radiologists who had undergone centralised training provided by the lead centre [University College London Hospital (UCLH)]. Radiologists were provided with clinical details including PSA levels, DRE findings and any other risk factors such as a family history of prostate cancer.

Images were reported in sequence, with T2-weighted images reported first, T2-weighted and diffusion- weighted images reported together and then a third report issued for T2-weighted with diffusion-weighted and dynamic contrast-enhanced scans together. The reporting form is shown inFigure 7. Future analyses will investigate whether or not both diffusion-weighted and dynamic contrast-enhanced images are required. As DCE requires a contrast agent (with its need for intravenous access, medical supervision and contrast- related risks) and an additional 10–15 minutes of scan time, it will be useful to determine whether or not this additional resource use and cost is necessary.

A five-point Likert scoring system66,67,72was used to indicate the probability of cancer (1, highly likely to

be benign; 2, likely to be benign; 3, equivocal; 4, likely to be malignant; 5, highly likely to be malignant). The prostate was divided into 12 regions of interest and each region was scored from 1 to 5. In addition, each lesion was identified and scored separately and the longest axial diameter, lesion volume, ADC value and contrast enhancement curve type were recorded.73–76From these observations, an overall score of

1–5 (using the same definitions) was assigned to the whole prostate. This was carried out for‘any cancer’ and for definitions 1 and 2 of CS cancer (seeDefinitions of clinically significant prostate cancer).

TABLE 3 Multiparametric magnetic resonance imaging scan specification

TR TE Flip angle, ° Plane Slice thickness [mm (gap)] Matrix size Field of view (mm) Time from scan

T2 TSE 5170 92 180 Axial, coronal, sagittal

3 (10%) 256 × 256 180 × 180 3 minutes 54 seconds (ax) VIBE at multiple

flip angles for T1 calculation (optional)

VIBE fat sat 5.61 2.52 15 Axial 3 192 × 192 260 × 260 Continue for

≥5 minutes 30 seconds after contrast Diffusion (b=0, 150, 500, 1000) 2200 Minimum (<98) Axial 5 172 × 172 260 × 260 5 minutes 44 seconds (16 averages) Diffusion (b=1400) 2200 Minimum (<98) Axial 5 172 × 172 320 × 320 3 minutes 39 seconds (32 averages)

VIBE, volumetric interpolated breath-hold examination. Note

Reproduced from El-Shater Bosailyet al.16

© 2015 The Authors. Published by Elsevier Inc. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/.

METHODS

NIHR Journals Library www.journalslibrary.nihr.ac.uk

For the primary outcome, an overall score of≥3 was used to indicate a suspicious scan in relation to CS cancer (i.e. a positive mpMRI score). This reflects the level at which further tests (e.g. biopsy) would be considered if mpMRI were to be introduced into the diagnostic pathway in the future. To assess interobserver agreement, 132 scans from the lead site were rereported by a blinded second radiologist based at that site. The values used in the analyses were those from the original reporter.

The results of the mpMRI could be unblinded by the radiologist if the mpMRI revealed an enlarged prostate volume of>100 ml, which would be impossible to sample every 5 mm because of the interference of the

bony pelvic arch. This might have reduced the number of‘negative’prostate results in the final analyses. The mpMRI could also be unblinded if there was evidence of stage T4 prostate cancer or involved lymph nodes or colorectal/bladder invasion. This might have had a detrimental impact on the performance characteristic of mpMRI, as such tumours were more likely to be detected. The presence of other cancers such as bladder or colorectal cancers was also a criterion for withdrawal. Withdrawal was deemed appropriate in these men as expedited referral for biopsy and treatment was required. These withdrawals were unlikely to have an impact on the primary or secondary outcomes.

The standard test: transrectal ultrasound-guided biopsy

Transrectal ultrasound-guided biopsy of the prostate was carried out after the TPM-biopsy (seeThe reference test: transperineal template prostate mapping biopsy), under the same general/spinal anaesthesia. This was to ensure that the results for the reference test (i.e. TPM-biopsy) were obtained in an optimal fashion in a biopsy-naive gland that had not undergone swelling and distortion. It also theoretically minimised the risk of infection as the potential for faecal contamination was restricted to the end of the procedure. The surgeon carrying out the biopsy procedure was blind to the mpMRI results so that suspicious areas would not

be targeted during the TRUS-guided biopsy and the fidelity of the TPM-biopsy reference test was maintained. TRUS-guided biopsies were taken as per international guidelines77and incorporated 10

–12 core biopsies. Each core was identified and potted separately. The TPM-biopsies and TRUS-guided biopsy sets from individual patients were sent to different pathologists to minimise review bias and work-up bias.

The reference test: transperineal template prostate mapping biopsy

Centres were selected for their prior experience in carrying out TPM-biopsies and training was provided to all centres to enable them to conduct TPM-biopsies in accordance with the PROMIS protocol.

Related documents