Diagnostic Performance of Prostate Imaging Reporting and Data …€¦ · data system version 2 Prostate cancer Magnetic resonance imaging Meta-analysis Abstract Context: In 2015,

Page 1

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

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journal homepage: www.europeanurology.com

Platinum Priority – Review – Prostate CancerEditorial by Jelle Barentsz, Maarten de Rooij, Geert Villeirs and Jeffrey Weinreb on pp. 189–191 of this issue

Diagnostic Performance of Prostate Imaging Reporting and Data

System Version 2 for Detection of Prostate Cancer: A Systematic

Review and Diagnostic Meta-analysis

Sungmin Woo a[2_TD$DIFF]

,y, Chong Hyun Suh b,c,y, Sang Youn Kim a,*, Jeong Yeon Cho a,d, Seung Hyup Kim a,d

a Department of Radiology, Seoul National University College of Medicine, Seoul, Korea; b Department of Radiology and Research Institute of Radiology,

University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; c Department of Radiology, Namwon Medical Center, Jeollabuk-do,

Republic of Korea; d Institute of Radiation Medicine and Kidney Research Institute, Seoul National University Medical Research Center, Seoul, Korea

Article info

Article history:

Accepted January 25, 2017

Associate Editor:

Giacomo Novara

Keywords:

Prostate imaging reporting and

data system version 2

Prostate cancer

Magnetic resonance imaging

Meta-analysis

Abstract

Context: In 2015, the updated Prostate Imaging Reporting and Data System version 2(PI-RADSv2) for the detection of prostate cancer (PCa) was established. Since then,several studies assessing the value of PI-RADSv2 have been published.Objective: To review the diagnostic performance of PI-RADSv2 for the detection of PCa.Evidence acquisition: MEDLINE and EMBASE databases were searched up to December7, 2016. We included diagnostic accuracy studies that used PI-RADSv2 for PCa detection,using prostatectomy or biopsy as the reference standard. The methodological qualitywas assessed by two independent reviewers using the Quality Assessment of DiagnosticAccuracy Studies-2 tool. Sensitivity and specificity of all studies were calculated. Resultswere pooled and plotted in a hierarchical summary receiver operating characteristic plotwith further exploration using meta-regression and multiple subgroup analyses. Head-to-head comparison between PI-RADSv1 and PI-RADSv2 was performed for availablestudies.Evidence synthesis: Twenty-one studies (3857 patients) were included. The pooledsensitivity was 0.89 (95% confidence interval [CI] 0.86–0.92) with specificity of 0.73(95% CI 0.60–0.83) for PCa detection. Proportion of patients with PCa, magnetic fieldstrength, and reference standard were significant factors affecting heterogeneity(p < 0.01). Multiple subgroup analyses showed consistent results. In six studies per-forming head-to-head comparison, PI-RADSv2 demonstrated higher pooled sensitivityof 0.95 (95% CI 0.85–0.98) compared with 0.88 (95% CI 0.80–0.93) for PI-RADSv1(p = 0.04). However, the pooled specificity was not significantly different (0.73 [95%CI 0.47–0.89] vs 0.75 [95% CI 0.36–0.94], respectively; p = 0.90).Conclusions: PI-RADSv2 shows good performance for the detection of PCa. PI-RADSv2has higher pooled sensitivity than PI-RADSv1 without significantly different specificity.Patient summary: We reviewed all previous studies using Prostate Imaging Reportingand Data System version 2 (PI-RADSv2) for prostate cancer detection. We found that theupdated PI-RADSv2 shows significant improvement compared with the original PI-RADSv1.

soc

# 2017 European As

y These authors contributed equally.* Corresponding author. Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. Tel. +82 2 2072 4897; Fax: +82 2 743 6385.

[email protected] (S.Y. Kim).

E-mail address: iwishlu

http://dx.doi.org/10.1016/j.eururo.2017.01.0420302-2838/# 2017 European Association of Urology. Published by Elsevier

iation of Urology. Published by Elsevier B.V. All rights reserved.

B.V. All rights reserved.

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E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 1 7 7 – 1 8 8178

1. Introduction

Prostate cancer (PCa) is the second leading cause of cancer-

related mortality in Western men [1]. With the recent

technological advancements and growing availability,

multiparametric magnetic resonance imaging (mpMRI)

currently is increasingly being used for guiding several

aspects of PCa management, including detection, staging,

and treatment planning [2]. Despite abundant evidence in

the literature reporting high accuracy of mpMRI for PCa

diagnosis, widespread acceptance has been hampered by

several factors including difficulty of interpretation, lack of

standardized criteria for interpretation (ie, use of Likert

scales based on the radiologist’s subjective level of

suspicion for PCa), and resulting substantial inter-reader

variability [3,4].

To bring standardization to the evaluation and

reporting of mpMRI of the prostate, the European Society

of Urogenital Radiology (ESUR) published a guideline

termed Prostate Imaging Reporting and Data System (PI-

RADS) in 2012 [5]. PI-RADS was generated based on

expert consensus and provides a detailed scoring system

for each MRI sequence (T2-weighted imaging [T2WI],

diffusion-weighted imaging [DWI], dynamic contrast-

enhanced MRI [DCE-MRI], and MR spectroscopy) for the

presence of clinically significant PCa (csPCa). Several

investigators have validated the accuracy and reproduc-

ibility of PI-RADS, and a recent meta-analysis reported

pooled sensitivity and specificity of 0.78 and 0.79,

respectively [6]. However, as there was no guideline for

the generation of an overall score, different research

groups utilized various measures for this purpose—some

used a sum of the scores from each sequence (ranging

from 3 to 15), whereas others used an overall score of 1–5

[7,8]. Furthermore, emerging data questioned the value of

curve-type analysis of DCE-MRI [9]. In addition, investi-

gators suggested that some sequences may be more

important in determining the likelihood of PCa (ie, DWI in

the peripheral zone [PZ] and T2WI in the transition

zone [TZ]) rather than equal weighting for all sequences

[10].

To address these issues, the ESUR and American College

of Radiology recently released the updated PI-RADS version

2 (PI-RADSv2) [11]. The main changes from PI-RADSv1 to PI-

RADSv2 are the following: (1) introduction of dominant

sequences according to zonal anatomy (DWI for the PZ and

T2WI for the TZ), (2) limited contribution of DCE-MRI data

as merely presence and absence of early focal enhancement,

and (3) generation of an overall score (1–5) integrating

findings across all MRI sequences.

Since then, several studies assessing the value of PI-

RADSv2 have been published. However, the diagnostic

performance of this new scoring system has not been

evaluated systematically. Therefore, the purpose of our

study was to assess the diagnostic performance of PI-

RADSv2 for the detection of PCa. In addition, we aimed

to compare the diagnostic performance of PI-RADSv1

and PI-RADSv2 in studies available for head-to-head

comparison.

2. Evidence acquisition

This meta-analysis was performed and written according to

the preferred reporting items for systematic reviews and

meta-analyses (PRISMA) guidelines [12].

2.1. Literature search

A computerized search of MEDLINE and EMBASE up to

December 7, 2016, was performed in order to identify

studies evaluating the diagnostic performance of PI-RADSv2

for the detection of PCa. The search query combined

synonyms for PCa, MRI, and PI-RADS as follows: (prostate

cancer OR prostatic cancer OR prostate neoplasm OR

prostatic neoplasm OR prostate tumor OR prostatic tumor

OR prostate carcinoma OR prostatic carcinoma OR PCa) AND

(magnetic resonance imaging OR MRI OR MR) AND

(prostate imaging reporting and data system OR pi-rads

OR pi rads OR pirads). Bibliographies of identified articles

were also screened to expand the scope of search. Our

search was limited to publications in English.

2.2. Study selection

2.2.1. Inclusion criteria

Studies were included if they satisfied all the following

requirements according to the PICOS criteria [12]: (1)

included patients with suspected or diagnosed PCa; (2) for

index test, mpMRI of the prostate including all required

sequences of T2WI, DWI, and DCE-MRI was performed and

assessed with a PI-RADSv2 scoring system; (3) for

comparison, a reference standard based on the histopatho-

logical examination of radical prostatectomy or biopsy was

used; (4) results were reported in sufficient detail for the

reconstruction of 2 � 2 tables and determination of

sensitivity and specificity at specified cutoff values for

evaluating the diagnostic performance of PI-RADSv2; and

(5) studies had to be original articles.

2.2.2. Exclusion criteria

Studies were excluded if any of the following criteria were

met: (1) studies involving <10 patients; (2) review articles,

guidelines, consensus statements, letters, editorials, and

conference abstracts; (3) studies using only PI-RADSv1 for

the evaluation of mpMRI of the prostate; (4) studies focusing

on topics other than using the PI-RADSv2 system for

diagnosing PCa (ie, staging and prediction of biochemical

recurrence); and (5) studies with overlapping patient

population.

Two reviewers (S.W. and C.H.S., with 3 yr of experience in

performing systematic reviews and meta-analyses) inde-

pendently evaluated the eligibility of the selected studies

from the literature. Disagreements, if present between the

two reviewers, were resolved by consensus via discussion

with a third reviewer (S.Y.K.).

2.3. Data extraction and quality assessment

We extracted the following data regarding study design and

results from the selected studies using a standardized form:

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E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 1 7 7 – 1 8 8 179

1. S

tudy characteristics—authors, year of publication,

country and institution of origin, duration of patient

recruitment, and study design (prospective vs retrospec-

tive and consecutive or not)

2. D

emographic and clinical characteristics—sample size,

number of patients with PCa, patient age, prostate-

specific antigen (PSA) level and Gleason score, number of

previous biopsies, and PCa diagnosis prior to mpMRI

3. T

echnical characteristics of mpMRI—scanner model and

manufacturer, magnetic field strength (1.5 vs 3 T), coil

type (endorectal vs pelvic phased array), and specific

sequences used (T2WI, DWI, DCE, or MR spectroscopy)

4. I

nterpretation of mpMRI—number of reviewers and

experience in prostate mpMRI, independent or consensus

reading, and blinding to clinicopathological information

5. R

eference standard—type of reference standard (radical

prostatectomy, targeted biopsy, or systematic biopsy),

interval between MRI and pathology, outcomes assessed

(any PCa vs csPCa), definition of csPCa (studies assessing

‘‘clinically significant’’, ‘‘aggressive’’, or ‘‘high-grade’’ PCa

were all considered to assess csPCa; however, only

studies that used the definition as provided by the PI-

RADSv2 guideline [Gleason score >7 [3 + 4], volume

>0.5 ml, or extraprostatic extension] were considered

not to have concern for applicability), separate analysis

for the PZ and TZ, and type of analysis (per patient vs per

lesion)

6. D

iagnostic performance of PI-RADSv2 including criteria

or cutoff values (in case of multiple readers, the results of

the most experienced reader were extracted for this

meta-analysis)

The methodological quality of the included studies was

assessed using tailored questionnaires and criteria provided

by Quality Assessment of Diagnostic Accuracy Studies-2

[13]. Data extraction and quality assessment were per-

formed independently by two reviewers (S.W. and C.H.S.).

All disagreements were resolved by consensus through

discussion with the third reviewer (S.Y.K.).

2.4. Data synthesis and analysis

The diagnostic performance of PI-RADSv2 for the detection

of PCa was the primary outcome for this meta-analysis. In

addition, a comparison between the diagnostic perfor-

mance of PI-RADSv2 and that of PI-RADSv1 using studies

that reported head-to-head comparison data of the two PI-

RADS versions was considered a secondary outcome.

Pooled estimates of sensitivity and specificity were

calculated using hierarchical logistic regression modeling

including bivariate modeling and hierarchical summary

receiver operating characteristic (HSROC) modeling

[14]. For graphical presentation of the results, an HSROC

curve with 95% confidence region and prediction region was

plotted. Publication bias was evaluated using the Deeks’

funnel plot, and statistical significance was tested with the

Deeks’ asymmetry test [15].

We performed [3_TD$DIFF]meta-regression analyses to investigate

the cause of heterogeneity. The following covariates were

considered for the bivariate model: (1) proportion of

patients with PCa (>50% vs �50%), (2) magnet strength

of MRI (3 vs 1.5 T), (3) use of endorectal coil, (4) cutoff value

(�4 vs�3), (5) reference standard (radical prostatectomy vs

biopsy), and (6) type of analysis (per patient vs per lesion).

In addition, multiple subgroup analyses were performed for

cutoff value, outcome, and previous biopsy history to assess

various clinical settings: (1) a cutoff value of �4 for all

studies, (2) a cutoff value of �3 for all studies, (3) a cutoff

value of�4 for determining any PCa, (4) a cutoff value of�3

for determining any PCa, (5) a cutoff value of �4 for

determining csPCa, (6) a cutoff value of �3 for determining

csPCa, (7) a cutoff value of �4 in studies using per-patient

analysis, (8) a cutoff value of �4 in studies using per-lesion

analysis, (9) studies analyzing PZ PCa, (10) studies analyzing

TZ PCa, (11) patients without previous biopsies, and (12)

patients [4_TD$DIFF]with previous biopsies. The ‘‘metandi’’ and ‘‘midas’’

modules in Stata 10.0 (StataCorp LP, College Station, TX,

USA) and ‘‘mada’’ package in R software version 3.2.1 (R

Foundation for Statistical Computing, Vienna, Austria) were

used for statistical analyses, with p < 0.05 signifying

statistical significance.

3. Evidence synthesis

3.1. Literature search

A systematic literature search initially identified 287 arti-

cles. After removing 46 duplicates, screening of the

241 titles and abstracts yielded 105 potentially eligible

articles. Full-text reviews were performed, and 84 studies

were excluded for the following reasons: not in the field of

interest (n = 80, including 68 studies that used only PI-

RADSv1), insufficient data to reconstruct 2 � 2 tables

(n = 2), and shared study population with other studies

(n = 2). Ultimately, 21 original articles including a total of

3857 patients assessing the diagnostic performance of PI-

RADSv2 were included in the meta-analysis [16–36]. No

additional studies were identified via screening the

bibliographies of these 21 studies. Among them, 15 studies

including 3099 patients dealt with PI-RADSv2 alone,

whereas six studies including 758 patients provided a

head-to-head comparison between PI-RADSv1 and PI-

RADSv2 [16,20,21,28,32,33]. The detailed study selection

process is described in Fig. 1.

3.2. Characteristics of included studies

Patient characteristics are shown in Table 1. The size of the

study population ranged from 49 to 456 patients, with the

percentage of those with PCa ranging from 37% to 100%. The

patients had a median age of 62–69.6 yr, median PSA of

3.97–15 ng/ml, and a Gleason score ranging from 5 to

10. Patients had already been diagnosed with PCa prior to

MRI in all or some of the study populations in seven studies

[16,17,22,26,27,32,35]. Biopsy was performed before MRI in

seven studies [16,21–23,26,27,35], all patients were biopsy-

naıve in three studies [18,25,34], both patient types were

included in three studies [28,32,33], and data regarding

Page 4

[(Fig._1)TD$FIG]

Fig. 1 – PRISMA flow diagram showing study selection process for meta-analysis. a Included original articles for qualitative and quantitative analysesare references [16–36]. MRI = magnetic resonance imaging; PI-RADS = Prostate Imaging Reporting and Data System; PRISMA = Preferred ReportingItems for Systematic Reviews and Meta-analyses.

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 1 7 7 – 1 8 8180

previous biopsy were not reported in the remaining eight

studies.

Characteristics of the studies are summarized in

Table 2. MRI was performed using 3-T scanners in 16 studies

[16–18,20,24–33,35,36], 1.5-T scanners in four studies

[19,21–23], and either 3 or 1.5 T in one study [34]. Endor-

ectal coils were used in seven studies [19,21–25,29]. In all

studies, the mpMRI protocol consisted of T2WI, DWI, and

DCE-MRI. The reference standard was radical prostatec-

tomy in five studies [16,22,26,27,35], a combination of

systematic and targeted biopsies in seven studies

[17,20,23,25,29,34,36], and only targeted biopsy in seven

studies [19,21,24,28,30,32,33]; the reference standard was

not consistent throughout the study population in two

studies [18,31]. PI-RADSv2 scoring was performed by one to

five radiologists, either in consensus or independently. The

level of experience of the radiologists was heterogeneous,

ranging from 4 to 22 yr of experience in the prostate. In

most studies, the readers were blinded; however, in three

studies, the radiologists were aware that the patients had

biopsy-proven PCa [22,26,35], and five studies were not

explicit regarding blinding [18,19,30,32,36]. In the majority

of the studies, the interval between MRI and the reference

standard was less than 6 mo; however, the details were not

reported in 10 studies [16–18,24,27–30,32,33]. PCa was

separately assessed according to zonal anatomy in seven

studies [20,24,25,28,30,31,33]. However, in one study [31],

only PCa in the PZ could be evaluated, as no detailed data

were provided in the article and the attempt to contact the

authors for provision of further information was unsuc-

cessful. Regarding the outcome assessed, seven studies

evaluated any cancer [17,19,20,23,25,28,31,33], eight eval-

uated clinically significant cancer [18,22,26,27,30,34–36],

and six evaluated both [16,21,24,29,32]. With regard to

cutoff values, 13 studies used �4 [16,18–21,24–

28,30,31,35], four studies used �3 [32–34,36], and four

studies used both [17,22,23,29]. The location of PCa was

separately reported by the PZ and TZ in six studies

[20,24,25,28,30,33].

3.3. Quality assessment

Overall, the quality of the studies was not considered high,

mainly due to the patient selection domain (Fig. 2).

Regarding the patient selection domain, there was generally

a high risk of bias as all but four of the studies were

retrospective in nature [16–18,20–23,25–28,30,32–

36]. Seven studies were considered to have high concern

for applicability, as all or some of the patients had a

pathological diagnosis of PCa prior to MRI

[16,17,22,26,27,32,35]. Regarding the index test domain,

there was a high risk of bias in nine studies. In three of nine

studies, reviewers were aware that patients had biopsy-

proven PCa [22,26,35]. In the other six studies, the cutoff

value for determining PCa was not specified prior to

interpretation [16,20,29,31,33,34]. Only one study had

concern for applicability, as PI-RADSv2 scores were

indirectly generated from existing clinical radiological

Page 5

Table 1 – Patient characteristics

First author (year) Origin Duration ofpatient

recruitment

Patients(n)

Patientswith

PCa (n)

Age (yr) PSA (ng/ml) Gleason score No. ofpreviousbiopsies

PCadiagnosis

before MRI

Country Institution Median Range Median Range Median Range

Auer (2016) [16] Austria Medical University of Innsbruck,

Medizinische Hochschule

Hannover

NR 50 NR 63a NR 7.3 a NR 7 (3 + 4) 6–10 �1 Yes (all)

Baldisserotto (2016) [17] Brazil Pontifıcia Universidade Catolica

do Rio Grande do Sul

2013.6–2015.6 54 33 65.9 a 53–81 8.4 a 3–31 7 (3 + 4) 6–9 NR Yes (some)

De Visschere (2017) [18] Belgium Ghent University Hospital 2011.5–2014.12 245 144 66 44–85 9 1.4–935.5 7 (3 + 4) �6 0 No

El-Samei (2016) [19] Egypt Al-Azher University, El-Minia

University

2014.5–2015.10 55 38 62 a 51–79 NR NR 7 6–10 NR No

Feng (2016) [20] China Tongji Hospital 2013.6–2015.7 401 150 64.4 a 34–88 10.7 0.2–1763 7 (4 + 3) �6–�8 NR NR

Kasel-Seibert (2016) [21] Germany University Hospital Jena 2013.7–2015.3 82 31 65 48–81 13 1–111 7 (3 + 4) 6–9 1–5 No

Lin (2016) [22] Brazil, Taiwan Ribeirao Preto School of

Medicine, China Medical

University, Ribeirao Preto School

of Medicine

2011.5–2014.6 49 49 63 46–73 13.27 1.8–41.4 �1 Yes (all)

Martorana (2016) [23] Italy University of Modena and

Reggio Emilia, Perugia

University

2014.1–2016.2 157 79 65 47–79 b 10.7 1–75 6 6–8 1–3 No

Mertan (2016) [24] USA National Cancer Institute 2015.3–2015.9 62 38 65.5 50.3–76.6 7.1 0.5–863 7 (3 + 4) 6–9 NR NR

Muller (2015) [25] USA,

the Netherlands

National Cancer Institute, AMC

University Hospital, Edward

Hebert School of Medicine

2011.12–2014.5 94 94 62 37–79 8.51 0.7–51.1 7 (3 + 4) 6–10 0 No

Park (2016) [26] South Korea Samsung Medical Center 2012.1–2014.12 456 456 65 46–81 3.97 3.8–4.2 NR �6 �1 Yes (all)

Park (2016) [27] South Korea Yonsei University College of

Medicine

2012.1–2013.3 425 425 NR NR NR 1.4–156.9 5–6 5–10 �1 Yes (all)

Polanec (2016) [28] Vienna Medical University of Vienna,

Confraternitat Vienna

2011.6–2015.9 65 NR 65.3 a 62.3–87.4 10.8 a 4.2–74.5 7 (4 + 3) 6–9 �0 No

Rastinehad (2015) [29] USA Icahn School of Medicine at

Mount Sinai, Fox Chase Cancer

Center, National Institutes of

Health, Hofstra North Shore LIJ

School of Medicine

2012.2–2014.11 312 202 65.1 60.3–70.3 b 7.3 5.0–11.4 b NR NR NR No

Rosenkrantz (2016) [30] USA NYU Langone Medical Center 2013.9–2015.2 343 134 64 NR 5.8 NR 7 (3 + 4) 6–9 NR NR

Stanzione (2016) [31] Italy University ‘‘Federico II’’,

Ospedale S. Maria delle Grazie

NR 82 34 65 a 43–84 8.8 a NR 7 (3 + 4) 6–9 NR No

Tan (2016) [32] USA, Taiwan UCLA, Cathay General Hospital,

Hoag Hospital

2013.3–2016.12 106 63 66.5 43–79 7.9 5.6–10.6 7 (3 + 4) 6–10 �0 Yes (some)

Tewes (2016) [33] Germany Hannover Medical School,

Klinikumder Region Hannover

2012.12–2014.12 54 31 69.6 a NR 8.7 a NR 6 6–9 �0 No

Washino (2017) [34] Japan Jichi Medical University Saitama

Medical Center

2010.6–2014.4 288 159 69 64–74 b 7.5 5.5–11 b NR NR 0 No

Woo (2016) [35] South Korea Seoul National University

College of Medicine

2011.1–2013.12 105 105 69 49–79 8.22 0.9–44.2 7 6–7 �1 Yes (all)

Zhao (2016) [36] China Peking University First Hospital 2010.11–2013.12 372 185 68.5 a NR 15 a NR 7 6–10 NR No

MRI = magnetic resonance imaging; NR = not reported; PCa = prostate cancer; PSA = prostate-specific antigen.a Mean.b Interquartile range.

EU

RO

PE

AN

UR

OL

OG

Y7

2(

20

17

)1

77

–1

88

18

1

Page 6

Table 2 – Study characteristics

Study Reader MRI

First author

(year)

Design Consecutive

enrollment

Reference

standard

MRI–

reference

standard

interval

No. of

readers

Experience

(yr)

Blinding Magnet

strength

(T)

Vendor Model Endorectal

coil

PI-RADSv2

application

Cutoff

values

Localization Type of

analysis

Outcome

assessed

Definition

of csPCa

Auer

(2016) [16]

Retrospective Yes RP NR 1 >5 Yes 3 Siemens Skyra No Strict 4 Whole Lesion Any +

csPCa

GS �7

(4 + 3)

Baldisserotto

(2016) [17]

Retrospective Yes STRUSGB + targeted

MRI–TRUS biopsy

(cognitive) or RP

NR 2

Independent

>10/1 Yes 3 GE SignaHDxt No Strict 3, 4 Whole Patient Any

De Visschere

(2017) [18]

Retrospective NR STRUSGB or RP NR NR NR NR 3 Siemens Trio No Strict 4 Whole Patient csPCa GS �7,

�0.5 cc,

or EPE

El-Samei

(2016) [19]

NR NR Targeted MRI–TRUS

biopsy

�2 wk NR NR NR 1.5 Phillips Gyroscan Yes Strict 4 Whole Lesion Any

Feng

(2016) [20]

Retrospective Yes STRUSGB + targeted

MRI–TRUS biopsy

(cognitive)

1–35 d 2

Consensus

5/4 Yes 3 Siemens Skyra No Strict 4 PZ, TZ Patient Any

Kasel-Seibert

(2016) [21]

Retrospective NR Targeted MRGB �7 d 2

Independent

10/<1 Yes 1.5 Siemens Avanto Yes Strict 4 Whole Lesion Any +

csPCa

GS �7

Lin

(2016) [22]

Retrospective NR RP �6 mo 2

Independent

12/5 Yes a 1.5 Phillips Achieva Yes Strict 3, 4 Whole Lesion csPCa GS �7 and

>0.5 cc

Martorana

(2016) [23]

Retrospective Yes TTB + targeted

MRI–TRUS biopsy

30–78 2

Consensus

4/4 Yes 1.5 Phillips Achieva Yes Strict 3, 4 Whole Lesion Any GS �7,

>0.5 cc,

or EPE

Mertan

(2016) [24]

Prospective Yes STRUSGB + targeted

MRI–TRUS biopsy

NR 1 >8 Yes 3 Phillips Achieva Yes Strict 4 PZ, TZ Lesion Any +

csPCa

GS �7

Muller

(2015) [25]

Retrospective Yes STRUSGB + targeted

MRI–TRUS biopsy

�6 wk 5

Independent

12/7/1/1/0.5 Yes 3 Phillips Achieva Yes Strict 4 PZ, TZ Lesion Any GS �7

(4 + 3)

Park

(2016) [26]

Retrospective Yes RP 21–48 2

Independent

14/3 Yes a 3 Phillips Achieva No Strict 4 Whole Patient csPCa GS �7,

�0.5 cc,

or EPE

Park

(2016) [27]

Retrospective NR RP NR 2

Independent

9/4 Yes 3 GE, Philips,

Siemens

DiscoveryMR750,

Achieva, Trio

No Strict 4 Whole Patient csPCa GS �7,

�0.5 cc,

or EPE

Polanec

(2016) [28]

Retrospective Yes Targeted MRGB NR 2

Independent

NR/NR Yes 3 Siemens Trio No Strict 4 PZ, TZ Lesion Any

Rastinehad

(2015) [29]

Prospective NR STRUSGB + targeted

MRI–TRUS biopsy

NR 3

Consensus

NR Yes 3 Siemens Verio Yes Calculated b 3, 4 Whole Patient Any +

csPCa

Epstein’s

criteria c for

systematic

and GS �7

or >0.5 cc

for targeted

biopsy

Rosenkrantz

(2016) [30]

Retrospective NR Targeted MRI–TRUS

biopsy

NR 2

Independent

8/3 NR 3 Siemens biobraphmMR/

Prisma/Skyra/Trio

No Strict 4 PZ, TZ Lesion csPCa GS �7

Stanzione

(2016) [31]

Prospective NR STRUSGB (�targeted

TRUSGB)

20–30 d 2

Independent

14/10 Yes 3 Siemens Trio No Strict 4 PZ Patient Any

Tan

(2016) [32]

Retrospective Yes Targeted MRGB NR 3

consensus

16/10 NR 3 Siemens Skyra, Trio, Verio No Strict 3 Whole Lesion Any +

csPCa

GS �7

Tewes

(2016) [33]

Retrospective Yes Targeted MRGB NR 2

Independent

5/2 Yes 3 Siemens Skyra No Strict 3 d PZ, TZ Patient Any

Washino

(2017) [34]

Retrospective NR TTB + targeted

MRI–TRUS biopsy

(cognitive)

0.5–1.6 mo 1 14 Yes 1.5 or 3 Toshiba Excelart Vantage/

Vantage Titan 3T

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reports based on PI-RADSv1 or an in-house scoring system

[29]. Regarding the reference standard domain, eight

studies had a high risk of bias. Seven were based on

either only systematic biopsy or targeted biopsy

[18,19,21,28,30,32,33]; in one study, targeted biopsy was

performed, but on lesions that were suspicious on

ultrasonography, and not on MRI [31]. Those in which

radical prostatectomy or a systematic plus targeted biopsy

(MRI guided, MRI–transrectal ultrasound fusion, or cogni-

tive) was used as the reference standard were considered to

have a low risk of bias. In 10 studies, the definition of

clinically significant cancer did not abide by those described

in the PI-RADSv2 guidelines, and therefore showed high

concern for applicability [16,21,22,24,29,30,32,34–36]. Re-

garding the flow and timing domain, two studies had a high

risk of bias as patients did not receive the same reference

standard [17,18].

3.4. Diagnostic accuracy of PI-RADSv2

The sensitivity and specificity of individual studies were

73–100% and 8–100%, respectively. The Q-test revealed that

substantial heterogeneity was present (p < 0.001). The

Higgins I2[3_TD$DIFF] statistics demonstrated substantial heterogeneity

in terms of the sensitivity (I2 = 85.55%) and considerable

heterogeneity in terms of the specificity (I2 = 95.30%). The

coupled forest plot of the sensitivity and specificity

demonstrated the absence of a threshold effect (Fig. 3).

The Spearman correlation coefficient between the sensitiv-

ity and the false-positive rate was 0.45 (95% confidence

interval [CI] 0.023–0.738), also indicating the lack of a

threshold effect.

For all 21 studies combined, the pooled sensitivity was

0.89 (95% CI 0.86–0.92) with specificity of 0.73 (95% CI 0.60–

0.83; Fig. 3). In the HSROC curve, there was a large

difference between the 95% confidence region and the 95%

prediction region, thus indicating heterogeneity between

the studies (Fig. 4). The area under the HSROC curve was

0.91 (95% CI 0.88–0.93). According to the Deeks’ funnel plot,

the likelihood of publication bias was low, with a p value of

0.75 for the slope coefficient (Fig. 5).

For the six studies that provided a head-to-head

comparison between PI-RADSv1 and PI-RADSv2, PI-RADSv2

demonstrated higher pooled sensitivity of 0.95 (95% CI

0.85–0.98) compared with 0.88 (95% CI 0.80–0.93) for PI-

RADSv1 (p = 0.04). However, the pooled specificity did not

show a significant difference between the two versions of

PI-RADS: 0.73 (95% CI 0.47–0.89) for v2 and 0.75 (95% CI

0.36–0.94) for v1 (p = 0.90).

3.5. Heterogeneity exploration

As we found a considerable heterogeneity among the

included studies, [3_TD$DIFF]meta-regression analyses were performed

(Supplementary Table 1). Among several potential vari-

ables, proportion of patients with PCa, magnetic field

strength, and reference standard were significant factors

affecting the heterogeneity (p < 0.01 for all). However,

among these three, only specificity according to the

Page 8

[(Fig._2)TD$FIG]

Fig. 2 – Grouped bar charts show (A) risk of bias and (B) concerns for applicability of 21 included studies using QUADAS-2. QUADAS-2 = QualityAssessment of Diagnostic Accuracy Studies-2.

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 1 7 7 – 1 8 8184

proportion of patients with PCa showed a statistically

significant and clinically meaningful difference: 0.65 (95%

CI 0.52–0.78) in studies �50% of patients with PCa versus

0.86 (0.75–0.97) in studies with >50% of patients with PCa.

Fig. 3 – Coupled forest plots of pooled sensitivity and specificity. Numbers areheterogeneity statistics are provided at bottom right corners. Horizontal lines

Otherwise, no clinically meaningful differences were seen:

for magnet strength (3 vs 1.5 T), sensitivity of 0.90 (95% CI

0.86–0.94) versus 0.89 (95% CI 0.81–0.97, p = 0.03) and

specificity of 0.73 (95% CI 0.59–0.86) versus 0.72 (95% CI

pooled estimates with 95% CI in parentheses. Correspondingindicate 95% CIs. CI = confidence intervals.

Page 9

[(Fig._4)TD$FIG]

Fig. 4 – Hierarchical summary receiver operating characteristic curve ofthe diagnostic performance of PI-RADSv2 for detecting prostate cancer.HSROC = hierarchical summary receiver operating characteristic; PI-RADSv2 = Prostate Imaging Reporting and Data System version 2.

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 1 7 7 – 1 8 8 185

0.44–1.00, p = 0.81); for reference standard (radical prosta-

tectomy vs biopsy), sensitivity of 0.89 (95% CI 0.83–0.95)

versus 0.91 (95% CI 0.88–0.94, p < 0.01) and specificity of

0.65 (95% CI 0.37–0.94) versus 0.73 (95% CI 0.58–0.87,

p = 0.48). Other variables, including the cutoff value, use of

[(Fig._5)TD$FIG]

Fig. 5 – Deeks’ funnel plot. A p value of 0.75 suggests that the likelihoodof publication bias is low.

endorectal coil, and type of analysis (per patient vs per

lesion), were not significant factors (p = 0.32–0.70).

3.6. Subgroup analysis

As there were four studies that used both �3 and �4

as cutoff values [17,22,23,29], or determined both any

cancer and clinically significant cancer as outcomes

[16,21,24,29,32], multiple subgroup analyses were per-

formed in order to assess various clinical settings (Supple-

mentary Table 2). Regarding cutoff values, the pooled

sensitivity was 0.89 (95% CI 0.84–0.92) with specificity of

0.74 (95% CI 0.58–0.85) for 17 studies using �4 [16–31,35],

whereas these were 0.95 (95% CI 0.89–0.97) and 0.47 (95%

CI 0.21–0.74) in eight studies using �3 [17,22,23,29,32–

34,36]. When we stratified studies according to the

outcome assessed, the following results were yielded: (1)

cutoff of �4 for determining any PCa, sensitivity of 0.89

(95% CI 0.83–0.93) with specificity of 0.80 (95% CI 0.62–

0.90); (2) cutoff of�3 for determining any PCa, sensitivity of

0.96 (95% CI 0.93–0.98) with specificity of 0.49 (0.29–0.70);

(3) for determining csPCa regardless of cutoff values,

sensitivity of 0.89 (95% CI 0.84–0.92) with specificity of

0.64 (95% CI 0.46–0.78); (4) cutoff of �4 for determining

csPCa, sensitivity of 0.90 (95% CI 0.85–0.94) with specificity

of 0.62 (95% CI 0.45–0.77); and (5) cutoff of �3 for

determining csPCa, sensitivity of 0.96 (95% CI 0.87–0.99)

with specificity of 0.29 (0.05–0.77). When the studies using

a cutoff value of �4 were separately assessed according to

the type of analysis, per-patient analysis in eight studies

[17,18,20,26,27,29,31,35] yielded pooled sensitivity of 0.89

(95% CI 0.81–0.93) with specificity of 0.76 (95% CI 0.60–

0.88), whereas per-lesion analysis in nine studies

[16,19,21–25,28,30] yielded pooled sensitivity of 0.87

(95% CI 0.83–0.91) with specificity of 0.70 (95% CI 0.44–

0.88).

Based on the localization of PCa, the pooled sensitivity

was 0.93 (95% CI 0.87–0.96) with specificity of 0.68 (95% CI

0.43–0.86) in seven studies analyzing PZ cancers

[20,24,25,28,30,31,33]. In identical studies, except for that

by Stanzione et al [31], which analyzed TZ cancers, the

pooled sensitivity and specificity were 0.88 (95% CI 0.77–

0.94) and 0.75 (95% CI 0.59–0.86), respectively.

Studies including patients without previous biopsies

yielded sensitivity of 0.82 (95% CI 0.72–0.90) and specificity

of 0.75 (95% CI 0.65–0.83), whereas the diagnostic perfor-

mance values were 0.87 (95% CI 0.80–0.92) and 0.71 (95% CI

0.42–0.89) in studies including patients with a history of

previous biopsy.

3.7. Discussion

In our meta-analysis, we assessed the diagnostic accuracy of

PI-RADSv2 for detecting PCa. The pooled sensitivity and

specificity of all 21 studies were 0.89 (95% CI 0.86–0.92) and

0.73 (95% CI 0.60–0.83), respectively. When comparing our

data with the only two existing meta-analyses using mpMRI

for detecting PCa, a trend toward higher sensitivity and

lower specificity can be inferred. In the study by de Rooij

Page 10

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 1 7 7 – 1 8 8186

et al [37], which evaluated seven studies using a combina-

tion of T2WI, DWI, and DCE-MRI, the pooled sensitivity and

specificity were 0.74 (95% CI 0.66–0.81) and 0.88 (95% CI

0.82–0.92), respectively. In a more recent meta-analysis by

Hamoen et al [6] which analyzed 14 studies using PI-

RADSv1, the pooled sensitivity and specificity were 0.78

(95% CI 0.70–0.84) and 0.79 (95% CI 0.68–0.86), respectively.

However, the comparison between the three studies merely

provided an indirect comparison. In order to address this

issue, we separately assessed a subgroup of studies using

both PI-RADSv1 and PI-RADSv2. In a head-to-head compar-

ison between them, PI-RADSv2 demonstrated higher pooled

sensitivity (0.95) compared with PI-RADSv1 (0.88, p = 0.04)

without a statistically significant difference in specificity

(0.73 vs 0.75, p = 0.90). This increase in sensitivity

compared with its predecessor may imply that the revisions

undertaken during the development of PI-RADSv2, includ-

ing the introduction of dominant sequences according to

zonal anatomy, limited contribution of DCE-MRI secondary

to DWI and T2WI, and specific guidelines for deriving an

integrated overall score, were, in fact, on the right track.

Especially, we speculate that the use of dominant

sequences, that is, DWI for the PZ and DCE-MRI for the

TZ, may have been crucial for the improved sensitivity

without a loss in specificity, as suggested by Baur et al [10].

Considering that one of the main intentions for the

generation of PI-RADS was to standardize reporting of

mpMRI in order to decrease variability and bring about

widespread acceptance and implementation in daily

practice, it was promising to find that nearly all (20 of

21) studies used PI-RADSv2 strictly according to published

guidelines [11]. Only one study formed PI-RADSv2 scores

from existing clinical radiological reports that were based

on PI-RADSv1 or an in-house scoring system [29]. This is an

improvement when compared with prior studies conducted

using PI-RADSv1, where investigators used varying meth-

ods in determining the overall score (overall five-point

score or sum of the scores from each modality) [6]. Still,

there is a need for further clarification regarding the cutoff

value for detecting PCa. In the studies included in our meta-

analysis, cutoff values were predefined in only six studies,

while the majority (15/21) were exploratory in nature,

testing multiple criteria. When using a cutoff value of �4,

sensitivity (0.89) and specificity (0.74) were generally good,

whereas using �3 yielded excellent sensitivity (0.95) and

poor specificity (0.47). These results may be taken into

consideration when generating the next updated PI-RADS.

For instance, using the former may be adequate for general

use of PI-RADS, whereas the latter could be proposed to be

indicated when a higher cancer detection rate is clinically

required (ie, persistently high PSA level despite a previously

negative biopsy).

In the current study, subgroup analyses were performed

to account for differences in outcomes (any cancer vs

clinically significant cancer). There was no significant

difference for using either outcome irrespective of whether

the criteria of �3 or �4 were used. However, the definition

of clinically significant cancer was different among the

13 studies. Only three studies defined csPCa strictly

according to the PI-RADSv2 guidelines (Gleason score >7

[3 + 4], volume >0.5 ml, or extraprostatic extension)

[11]. Most others used one or two of the three criteria.

Including only the former three studies may have provided

more robust results; yet it was not only pragmatic to

include all available studies, but this approach would

present a general overview of the existing literature, as it is

the first meta-analysis of studies currently dealing with PI-

RADSv2.

In this meta-analysis, we looked into the technical

aspects of MRI. [5_TD$DIFF]Meta-regression analyses revealed that the

use of endorectal coil was not a statistically significant

factor. Furthermore, although magnet strength showed

statistically significant differences between 3 and 1.5 T, this

did not reveal to be clinically meaningful (sensitivity of

0.90 vs 0.89, p = 0.03, respectively). Although there had

been debate over these two issues in the past, both 3 and

1.5 T are now well established, and the overall benefit of

using an endorectal coil is not evident [38,39]. The PI-

RADSv2 guidelines currently recommend either usage, and

the results of our study provide additional evidence to

support this.

Regarding the methods of analysis in the studies, there

was significant heterogeneity regarding reference standard

and type of analysis. Radical prostatectomy was the

reference standard in five studies, while the majority were

based on a combination of systematic and targeted biopsies.

The possibility of PCa despite negative biopsy results in the

latter group should be kept in mind. In addition, approxi-

mately half of the studies each reported outcomes in a per-

patient (n = 11) and per-lesion (n = 10) Manner. Per-lesion

analysis is known to take into account the performance of

localizing the disease; however, this was not shown to be a

significant factor in the [3_TD$DIFF]meta-regression analysis.

Our meta-analysis had some limitations. Nearly all

studies were retrospective in study design, resulting in a

high risk of bias for patient selection. It is possible that

pooling data from predominantly retrospective studies may

have led to increased diagnostic sensitivity [40]. In addition,

not only was performing a meta-analysis using only three

prospective studies technically unfeasible, but the derived

results would not be representative of the existing literature

on PI-RADSv2 as well. Furthermore, we used validated

methods for the systematic review and reported the data

using standard reporting guidelines, including PRISMA and

the guidelines of the Handbook for Diagnostic Test Accuracy

Reviews published by the Cochrane Collaboration

[12,41]. Another limitation is considerable heterogeneity

in our pooled analysis, which affected the general applica-

bility of our summary estimates. To explore the heteroge-

neity of our data, we performed [3_TD$DIFF]meta-regression and

multiple subgroup analyses. According to the analyses, the

proportion of patients with PCa, the magnetic field strength,

and the reference standard were significant factors affecting

the heterogeneity. Especially, the reference standard

included various methods, including radical prostatectomy

and a combination of systematic and targeted biopsies (ie,

MRI guided, MRI-transrectal ultrasound fusion, or cogni-

tive). Furthermore, the fact that various definitions were

Page 11

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 1 7 7 – 1 8 8 187

used for clinically significant cancer needs to be empha-

sized. Our analyses using [3_TD$DIFF]meta-regression and subgroup

analyses may explain some of the heterogeneity, but a

portion remains unexplained. Another important limitation

is the small number of included studies for head-to-head

comparison between PI-RADSv1 and PI-RADSv2. However,

we were able to elucidate statistically significant difference

in the sensitivity between the two versions using only six

studies, which have been published until now.

4. Conclusions

PI-RADSv2 shows good performance for the detection of PCa

with pooled sensitivity of 0.89 and specificity of 0.73. PI-

RADSv2 has higher pooled sensitivity compared with PI-

RADSv1 without significantly different specificity.

Author contributions: Sang Youn Kim had full access to all the data in the

study and takes responsibility for the integrity of the data and the

accuracy of the data analysis.

Study concept and design: Woo, Suh, S.Y. Kim.

Acquisition of data: Woo, Suh, S.Y. Kim.

Analysis and interpretation of data: Woo, Suh, S.Y. Kim.

Drafting of the manuscript: Woo.

Critical revision of the manuscript for important intellectual content: Suh,

S.Y. Kim, Cho, S.H. Kim.

Statistical analysis: Suh.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: S.Y. Kim, Cho, S.H. Kim.

Other: None.

Financial disclosures: Sang Youn Kim certifies that all conflicts of

interest, including specific financial interests and relationships and

affiliations relevant to the subject matter or materials discussed in the

manuscript (eg, employment/affiliation, grants or funding, consultan-

cies, honoraria, stock ownership or options, expert testimony, royalties,

or patents filed, received, or pending), are the following: None.

Funding/Support and role of the sponsor: None.

Appendix A. Supplementary data

Supplementary data associated with this article can be

found, in the online version, at http://dx.doi.org/10.1016/j.

eururo.2017.01.042.

References

[1] American Cancer Society. Key statistics for prostate cancer. www.

cancer.org/cancer/prostatecancer/detailedguide/

prostate-cancer-key-statistics.

[2] Hoeks CM, Barentsz JO, Hambrock T, et al. Prostate cancer: multi-

parametric MR imaging for detection, localization, and staging.

Radiology 2011;261:46–66.

[3] Ruprecht O, Weisser P, Bodelle B, Ackermann H, Vogl TJ. MRI of the

prostate: interobserver agreement compared with histopathologic

outcome after radical prostatectomy. Eur J Radiol 2012;81:456–60.

[4] Dickinson L, Ahmed HU, Allen C, et al. Scoring systems used for the

interpretation and reporting of multiparametric MRI for prostate

cancer detection, localization, and characterization: could stan-

dardization lead to improved utilization of imaging within the

diagnostic pathway? J Magn Reson Imaging 2013;37:48–58.

[5] Barentsz JO, Richenberg J, Clements R, et al. ESUR prostate MR

guidelines 2012. Eur Radiol 2012;22:746–57.

[6] Hamoen EH, de Rooij M, Witjes JA, Barentsz JO, Rovers MM. Use of

the Prostate Imaging Reporting and Data System (PI-RADS) for

prostate cancer detection with multiparametric magnetic reso-

nance imaging: a diagnostic meta-analysis. Eur Urol

2015;67:1112–21.

[7] Abd-Alazeez M, Ahmed HU, Arya M, et al. The accuracy of multi-

parametric MRI in men with negative biopsy and elevated PSA

level—can it rule out clinically significant prostate cancer? Urol

Oncol 2014;32, 45 e17–22.

[8] Rosenkrantz AB, Kim S, Lim RP, et al. Prostate cancer localization

using multiparametric MR imaging: comparison of Prostate Imag-

ing Reporting and Data System (PI-RADS) and Likert scales. Radiol-

ogy 2013;269:482–92.

[9] Hansford BG, Peng Y, Jiang Y, et al. Dynamic contrast-enhanced MR

imaging curve-type analysis: is it helpful in the differentiation of

prostate cancer from healthy peripheral zone? Radiology

2015;275:448–57.

[10] Baur AD, Maxeiner A, Franiel T, et al. Evaluation of the Prostate

Imaging Reporting and Data System for the detection of prostate

cancer by the results of targeted biopsy of the prostate. Invest

Radiol 2014;49:411–20.

[11] Weinreb JC, Barentsz JO, Choyke PL, et al. PI-RADS Prostate Imag-

ing-Reporting and Data System: 2015, version 2. Eur Urol

2016;69:16–40.

[12] Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for

reporting systematic reviews and meta-analyses of studies that

evaluate health care interventions: explanation and elaboration. J

Clin Epidemiol 2009;62:e1–34.

[13] Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The

development of QUADAS: a tool for the quality assessment of

studies of diagnostic accuracy included in systematic reviews.

BMC Med Res Methodol 2003;3:25.

[14] Suh CH, Park SH. Successful publication of systematic review and

meta-analysis of studies evaluating diagnostic test accuracy. Kore-

an J Radiol 2016;17:5–6.

[15] Deeks JJ, Macaskill P, Irwig L. The performance of tests of publica-

tion bias and other sample size effects in systematic reviews of

diagnostic test accuracy was assessed. J Clin Epidemiol

2005;58:882–93.

[16] Auer T, Edlinger M, Bektic J, et al. Performance of PI-RADS version 1

versus version 2 regarding the relation with histopathological

results. World J Urol 2017;35:687–93.

[17] Baldisserotto M, Neto EJ, Carvalhal G, et al. Validation of PI-RADS v.2

for prostate cancer diagnosis with MRI at 3T using an external

phased-array coil. J Magn Reson Imaging 2016;44:1354–9.

[18] De Visschere P, Lumen N, Ost P, Decaestecker K, Pattyn E, Villeirs G.

Dynamic contrast-enhanced imaging has limited added value

over T2-weighted imaging and diffusion-weighted imaging

when using PI-RADSv2 for diagnosis of clinically significant pros-

tate cancer in patients with elevated PSA. Clin Radiol 2017;72:23–

32.

[19] El-Samei HAE-KA, Amin MF, Hassan EE. Assessment of the accuracy

of multi-parametric MRI with PI-RADS 2.0 scoring system in the

discrimination of suspicious prostatic focal lesions. Egypt J Radiol

Nucl Med 2016;47:1075–82.

[20] Feng ZY, Wang L, Min XD, Wang SG, Wang GP, Cai J. Prostate cancer

detection with multiparametric magnetic resonance imaging: Pros-

tate Imaging Reporting and Data System version 1 versus version 2.

Chin Med J 2016;129:2451–9.

Page 12

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 1 7 7 – 1 8 8188

[21] Kasel-Seibert M, Lehmann T, Aschenbach R, et al. Assessment of PI-

RADS v2 for the detection of prostate cancer. Eur J Radiol

2016;85:726–31.

[22] Lin WC, Muglia VF, Silva GE, Chodraui Filho S, Reis RB, Westphalen

AC, Multiparametric MRI. of the prostate: diagnostic performance

and interreader agreement of two scoring systems. Br J Radiol

2016;89:20151056.

[23] Martorana E, Pirola GM, Scialpi M, et al. Lesion volume predicts

prostate cancer risk and aggressiveness: validation of its value

alone and matched with Prostate Imaging Reporting and Data

System score. BJU Int. In press. http://dx.doi.org/10.1111/bju.

13649.

[24] Mertan FV, Greer MD, Shih JH, et al. Prospective evaluation of the

Prostate Imaging Reporting and Data System version 2 for prostate

cancer detection. J Urol 2016;196:690–6.

[25] Muller BG, Shih JH, Sankineni S, et al. Prostate cancer: interobserver

agreement and accuracy with the revised Prostate Imaging Report-

ing and Data System at multiparametric MR imaging. Radiology

2015;277:741–50.

[26] Park JJ, Park BK. Role of PI-RADSv2 with multiparametric MRI in

determining who needs active surveillance or definitive treat-

ment according to PRIAS. J Magn Reson Imaging 2017;45:

1753–9.

[27] Park SY, Jung DC, Oh YT, et al. Prostate cancer: PI-RADS version

2 helps preoperatively predict clinically significant cancers. Radi-

ology 2016;280:108–16.

[28] Polanec S, Helbich TH, Bickel H, et al. Head-to-head comparison of

PI-RADS v2 and PI-RADS v1. Eur J Radiol 2016;85:1125–31.

[29] Rastinehad AR, Waingankar N, Turkbey B, et al. Comparison of

multiparametric MRI scoring systems and the impact on cancer

detection in patients undergoing MR US fusion guided prostate

biopsies. PLoS One 2015;10:e0143404.

[30] Rosenkrantz AB, Babb JS, Taneja SS, Ream JM. Proposed adjustments

to PI-RADS version 2 decision rules: impact on prostate cancer

detection. Radiology. In press. http://dx.doi.org/10.1148/radiol.

2016161124.

[31] Stanzione A, Imbriaco M, Cocozza S, et al. Biparametric 3T magnetic

resonance imaging for prostatic cancer detection in a biopsy-naive

patient population: a further improvement of PI-RADS v2? Eur J

Radiol 2016;85:2269–74.

[32] Tan N, Lin WC, Khoshnoodi P, et al. In-Bore 3-T MR-guided trans-

rectal targeted prostate biopsy: Prostate Imaging Reporting and

Data System version 2-based diagnostic performance for detection

of prostate cancer. Radiology. In press. http://dx.doi.org/10.1148/

radiol.2016152827.

[33] Tewes S, Mokov N, Hartung D, et al. Standardized reporting of

prostate MRI: comparison of the Prostate Imaging Reporting and

Data System (PI-RADS) version 1 and version 2. PLoS One

2016;11:e0162879.

[34] Washino S, Okochi T, Saito K, et al. Combination of PI-RADS score

and PSA density predicts biopsy outcome in biopsy naive patients.

BJU Int 2017;119:225–33.

[35] Woo S, Kim SY, Lee J, Kim SH, Cho JY. PI-RADS version 2 for

prediction of pathological downgrading after radical prostatec-

tomy: a preliminary study in patients with biopsy-proven Gleason

Score 7 (3 + 4) prostate cancer. Eur Radiol 2016;26:3580–7.

[36] Zhao C, Gao G, Fang D, et al. The efficiency of multiparametric

magnetic resonance imaging (mpMRI) using PI-RADS Version 2 in

the diagnosis of clinically significant prostate cancer. Clin Imaging

2016;40:885–8.

[37] de Rooij M, Hamoen EH, Futterer JJ, Barentsz JO, Rovers MM.

Accuracy of multiparametric MRI for prostate cancer detection: a

meta-analysis. Am J Roentgenol 2014;202:343–51.

[38] Shah ZK, Elias SN, Abaza R, et al. Performance comparison of 1.5-T

endorectal coil MRI with 3.0-T nonendorectal coil MRI in patients

with prostate cancer. Acad Radiol 2015;22:467–74.

[39] Mazaheri Y, Vargas HA, Nyman G, Akin O, Hricak H. Image artifacts

on prostate diffusion-weighted magnetic resonance imaging:

trade-offs at 1.5 Tesla and 3.0 Tesla. Acad Radiol 2013;20:1041–7.

[40] Deeks JJ. Systematic reviews in health care: systematic reviews of

evaluations of diagnostic and screening tests. BMJ 2001;323:157–62.

[41] Deeks JJWS, Davenport C. Guide to the contents of a Cochrane

diagnostic test accuracy protocol. In: Deeks JJ, Bossuyt PM, Gatsonis

C, editors. Cochrane handbook for systematic reviews of diagnostic

test accuracy version 1.0.0. Chapter 4. The Cochrane Collaboration;

2013 In: http://srdta.cochrane.org/.