EURURO Vol. 72 No. 2

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1. Introduction
Prostate biopsy with multiple samples using a standardized
template (standard biopsy [SB]) under transrectal ultra-
sound (TRUS) guidance is the current standard diagnostic
approach in suspicion of prostate cancer (PCa) , as
recommended by the European Association of Urology
guidelines .
Many biopsies are unnecessary or cannot detect clinically
significant PCa (csPCa) With the introduction of multi-
parametric magnetic resonance imaging (mpMRI) of the
prostate, investigators have reported improved PCa detec-
tion and localization Moreover, mpMRI can be useful to
more effectively select patients who are eligible for prostate
biopsy because of its high negative predictive value, mainly
in men with previous negative mapping results . Finally,
mpMRI allows the clinician to guide prostate biopsy
sampling. Some studies have reported comparable findings
of PCa detection rates (DRs) between mpMRI–targeted
biopsy and SB ; the latter approach has been described
as increasing csPCa detection in biopsy-naı¨ve patients, thus
decreasing the detection of nonsignificant PCa
The aim of this randomized prospective two-arm study
was to evaluate the diagnostic accuracy of the mpMRI
pathway itself and in comparison with the standard
pathway in biopsy-naı¨ve men.
2. Materials and methods
2.1. Study population and design
The study enrollment lasted from November 2014 to March 2016. It was
conducted in accordance with good clinical practice guidelines and the
ethical principles of the Declaration of Helsinki as amended in Hong
Kong. In addition, the study was approved by the local ethics committee
(San Luigi Gonzaga Hospital, Orbassano, Italy). The Consolidated
Standards of Reporting Trials flow diagram is shown in .
The eligibility criteria were (1) age 75 yr, (2) prostate-specific
antigen (PSA) level =15 ng/ml, (3) negative digital rectal examination
(DRE) results, and (4) signed informed consent. The exclusion criteria
were (1) previous prostate biopsy or surgery, (2) previous prostate
mpMRI, and (3) contraindication to mpMRI. No enrolled patients had
previously been included in published cohorts.
In total, 223 eligible patients scheduled for prostate biopsy in our
department were randomly assigned to one of the following arms: arm
A, mpMRI prior to prostate biopsy; arm B, SB of the prostate. In arm A, all
patients with mpMRI evidence of lesions suspicious for PCa were
submitted to mpMRI/TRUS fusion software-based targeted biopsy (TB;
arm A MRI+). In cases of negative mpMRI results, arm A patients
underwent SB (arm A MRI–).
The present randomized clinical trial compared the outcomes
between the two arms.
The primary end point was the comparison of the overall detection
rates of PCa and csPCa between arm A and arm B. The secondary end
points were (1) comparison of the overall DRs of PCa and csPCa between
arm A MRI+ and arm A MRI–, (2) comparison in terms of pathologic
results, (3) comparison of complication rates, and (4) follow-up of
patients in arm A MRI– and arm A MRI+ with negative biopsy results.
In this first report, the primary end point and the first two secondary
end points were reached and considered. The study is ongoing to
examine the remaining secondary end points.
2.2. Randomization
Immediately after signing a specific informed consent form, the patients
were randomized into either arm A or arm B.
2.2.1. Sequence generation
Patients were randomly assigned to arm A or arm B following a 1:1
simple randomization procedure according to a computer-generated
randomization list. The randomization list was prepared by an external
randomization manager. He was the only person to have possession of
the list, and he had no clinical involvement in the trial.
2.2.2. Allocation concealment and implementation
Different staff members (blinded to the randomization sequence)
evaluated the inclusion criteria and obtained the patients’ informed
consents. Immediately after this phase, staff members contacted the
external randomization manager, who assigned the patients to one of
the two groups.
Finally, independent staff members (F.M. and M.M.) planned the two
different diagnostic pathways, namely, mpMRI and different prostate
biopsies in arm A versus SB of the prostate in arm B.
2.3. Multiparametric magnetic resonance imaging
All of the patients in arm A underwent mpMRI according to the European
Society of Urogenital Radiology guidelines. The Prostate Imaging–
Reporting and Data System (PI-RADS) classification was used to describe
the lesions found . The mpMRI was performed at three centers with a
1.5-T scanner using a 32-channel phase array coil or four-channel phase
array coil combined with an endorectal coil. A description of mpMRI
acquisition is provided in Supplement 1 . Three experienced
radiologists analyzed the mpMRI findings. Lesions with a PI-RADS score
of 3 were considered suspicious for PCa.
2.4. Prostate biopsy
All of the patients underwent prostate biopsy in an ambulatory setting
according to the guidelines . TRUS was performed using a Hawk
Ultrasound scanner 2102 EXL with a biplanar transducer (B-K Medical,
Herlev, Denmark). Biopsies were performed using a disposable 18-gauge
biopsy gun with a specimen size of 18–22 mm (Bard Medical, Covington,
GA, USA) by two senior urologists. Both urologists had a level of
experience of >20 yr in SB and >1 yr in TB (>100 procedures per
urologist).
TB was performed using the BioJet fusion system (D&K Technolo-
gies, Barum, Germany), as previously described . The gland and
the regions of interest (ROIs) were contoured, and the prostate
contour was fused in real time with the TRUS image. Biopsies were
performed via either a transrectal (n = 55 [67.9%]) or transperineal
( n = 26 [32.1%]) approach based on the location of the ROI: transrectal
for ROIs in the peripheral zone and transperineal for ROIs in the
transition, central, or anterior zone. The patient was placed in the
lithotomy position. TB was performed on a maximum of two ROIs, and
three to six cores were obtained for biopsy from each lesion. Lesions
from the transition or central zone with a PI-RADS score of 3 were not
biopsied.
Twelve-core SB was performed according to the protocol by
Rodrı´guez-Covarrubias et al via a transrectal approach.
2.5. Pathologic analysis
Histopathologic examination was conducted by a uropathologist who
was blinded to the inclusion of each patient in the RCT and to the mpMRI
results, according to a standardized protocol
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