EURURO Vol. 72 No. 6

Introduction

Prostate-specific antigen (PSA) screening leads to increased

prostate cancer (PC) detection and a shift from advanced to

earlier disease stages

[1,2]

. However, PSA testing lacks

specificity, resulting in unnecessary biopsies

[3] .

Simulta-

neously, random transrectal ultrasound (TRUS)-guided

biopsy suffers from poor sampling, leading to under-

detection of PC in approximately 50% of cases compared

with radical prostatectomy (RP) specimen and transper-

ineal mapping biopsy

[4,5] .

Currently, the most promising

candidate to overcome these limitations is multiparametric

magnetic resonance imaging (mpMRI) using a standardized

reporting system (Prostate Imaging Reporting and Data

System [PI-RADS])

[6,7]

. Compared with RP specimens,

mpMRI detects 85–95% of index lesions and significant PC

(sPC)

[8,9]

. Fusion-targeted biopsies (FTBs) of suspicious

mpMRI lesions improve the detection of sPC by 30%

[10] .

To identify men with sPC and concurrently to avoid

unnecessary biopsies, multivariable risk-based approaches

have been introduced

[2,3,11]

. Using risk calculators (RCs)

built on European Randomized Study of Screening for PC

(ERSPC) data, Roobol et al

[2_TD$DIFF]

demonstrated that 33% of standard

biopsies can be avoided in men who are at risk of PC below

[8_TD$DIFF]

12.5%

[3] .

However, recent RCs do not include mpMRI data.

FTB of mpMRI-suspicious lesions alone is a promising

strategy to reduce overdetection of insignificant disease,

but MRI-invisible sPC is overlooked by such an approach

[10,12–14]

. Here, we added prebiopsy mpMRI to clinical

parameters and developed risk models (RMs) to determine

individual sPC risk using a validated biopsy approach

combining FTBs and transperineal systematic saturation

biopsies (SBs) as reference

[8] .

Patients and methods

2.1.

Study population

Consecutive patients were enrolled and registered into a prospective

database assessing MRI-targeted/TRUS fusion biopsy between 2012 and

2015. Institutional review board approval was obtained (S011/2011),

and all participants provided written informed consent. Subgroups were

reported previously

[8,15]

The study population consisted of 1159 retrospectively analyzed

patients. Inclusion criteria were mpMRI with PI-RADS scoring and fusion

biopsy at our department. In total, the sample consists of 670 (58%)

biopsy-naı¨ve men and 489 (42%) men with previous TRUS biopsy. A total

of 129 men under active surveillance and 15 men who had missing data

were excluded (Supplementary Fig. 1). For 660 biopsy-naı¨ve men and

355 men with previous TRUS biopsy, full data on PI-RADS, biopsy-

outcome, PSA, age, digital-rectal examination (DRE), prostate volume (PV),

prior biopsy, lesions on TRUS, and ERSPC-RCs were available. Those

samples served for RMdevelopment, internal validation, and comparisons

with ERSPC-RCs, PI-RADSv1.0, and combined ERSPC-RCs and PI-RADSv1.0.

2.2.

Imaging

All mpMRI examinations were performed using a 3 T system (Magnetom;

Siemens, Erlangen, Germany) using a multichannel-body-surface coil

(Supplementary Table 1). All image analyses were prospectively performed

according to PI-RADSv1.0 by or under the supervision of expert

uroradiologists (H.P.S., D.B., and M.C.R., with 7–12 yr experience in prostate

MRI)

[6] .

Overall, PI-RADS scores for each lesionwere determined on a five-

point Likert scale and entailed assignment of a separate score for each of the

T2-weighted, DW, and dynamic contrast-enhanced imaging sequences

[6]

. PV was calculated on T2-weighted images

( www.itksnap.org

2.3.

Biopsy protocol

All men underwent transperineal FTB with rigid software registration

using BiopSee (MedCom, Darmstadt, Germany) of MRI-suspicious

lesions first (2–5 cores, median 2 per lesion) and then SB adjusted to

PV (median 24 cores), as previously described

[8,15]

. Transperineal grid-

directed biopsy performed under general anesthesia is our standard

technique, the sPC-detection accuracy of which has been validated using

RP specimens

[8]

2.4.

Histopathology

Histopathological analyses were performed under the supervision of a

uropathologist (W.R.) specialized in prostate assessment according to

International Society of Urological Pathology standards. sPC was defined

as Gleason score (GS) 3 + 4.

Results and limitations:

PSA, prostate volume, digital-rectal examination, and PI-RADS

were significant sPC predictors and included in the RMs together with age. The ROC area

under the curve of the RM for biopsy-naı¨ve men was comparable with ERSPC-RC3 plus PI-

RADSv1.0 (0.83 vs 0.84) but larger compared with ERSPC-RC3 (0.81), refitted RC3 (0.80), and

PI-RADS (0.76). For postbiopsy men, the novel RM’s discrimination (0.81) was higher,

compared with PI-RADS (0.78), ERSPC-RC4 (0.66), refitted RC4 (0.76), and ERSPC-RC4 plus

PI-RADSv1.0 (0.78). Both RM benefits exceeded those of ERSPC-RCs and PI-RADS in the

decision regarding which patient to receive biopsy and enabled the highest reduction rate of

unnecessary biopsies. Limitations include a monocentric design and a lack of PI-RADSv2.0.

Conclusions:

The novel RMs, incorporating clinical parameters and PI-RADS, performed

significantly better compared with RMs without PI-RADS and provided measurable benefit

in making the decision to biopsy men at a suspicion of PC. For biopsy-naı¨ve patients, both

our RM and ERSPC-RC3 plus PI-RADSv1.0 exceeded the prediction performance compared

with clinical parameters alone.

Patient summary:

Combined risk models including clinical and imaging parameters pre-

dict clinically relevant prostate cancer significantly better than clinical risk calculators and

multiparametric magnetic resonance imaging alone. The risk models demonstrate a benefit

in making a decision about which patient needs a biopsy and concurrently help avoid

unnecessary biopsies.

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 8 8 8 – 8 9 6

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