Biparametric 3T Magentic Resonance Imaging for prostatic cancer detection in a biopsy-naïve patient population: a further improvement of PI-RADS v2?

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ContentslistsavailableatScienceDirect

European

Journal

of

Radiology

jo u r n al ho me p a g e : w w w . e l s e v i e r . c o m / l o c a t e / e j r a d

Biparametric

3T

Magentic

Resonance

Imaging

for

prostatic

cancer

detection

in

a

biopsy-naïve

patient

population:

a

further

improvement

of

PI-RADS

v2?

Arnaldo

Stanzione

a

_,

_Massimo

_Imbriaco

a,∗

_,

_Sirio

_Cocozza

a

_,

_Ferdinando

_Fusco

b

_,

Giovanni

Rusconi

a

_,

_Carmela

_Nappi

a

_,

_Vincenzo

_Mirone

b

_,

_Francesco

_Mangiapia

b

_,

Arturo

Brunetti

a

_,

_Alfonso

_Ragozzino

c

_,

_Nicola

_Longo

b

a_Department_of_Advanced_Biomedical_Sciences,_University_“Federico_II”,_Naples,_Italy

b_Department_of_{Neurosciences,}_Reproductive_Sciences_and_{Odontostomatology,}_University_“Federico_II”,_Naples,_Italy c_Department_of_Radiology,_Ospedale_S._Maria_delle_Grazie,_Pozzuoli,_Italy

a

r

t

i

c

l

e

i

n

f

o

Articlehistory: Received12September2016 Accepted10October2016 Keywords: Prostatecancer MRI Urologicdiseases Medicaloncology PI-RADS

a

b

s

t

r

a

c

t

Objectives:Toprospectivelydeterminethediagnosticaccuracyofabiparametric3Tmagneticresonance

imagingprotocol(BP-MRI)forprostaticcancerdetection,comparedtoamultiparametricMRIprotocol

(MP-MRI),inabiopsynaïvepatientpopulation.

Methods:Eighty-twountreatedpatients(meanage65±7.6years)withclinicalsuspicionofprostate

cancerand/oralteredprostate-speciﬁcantigen(PSA)levelsunderwentaMP-MRI,includingT2-weighted

imaging,diffusion-weightedimaging(withthecorrespondentapparentdiffusioncoefﬁcientmaps)and

dynamiccontrastenhancedsequence,followedbyprostatebiopsy.Tworadiologistsreviewedboththe

BP-MRIandtheMP-MRIprotocolstoestablisharadiologicaldiagnosis.Receiveroperatingcharacteristics

curveswereobtainedtodeterminethediagnosticperformanceofthetwoprotocols.

Results:ThemeanPSAlevelwas8.8±8.1ng/ml.Atotalof34prostatictumorswereidentiﬁed,witha

Gleasonscorethatrangedfrom3+3to5+4.Ofthese34tumors,29werelocatedwithintheperipheral

zoneand5inthetransitionalzone.BP-MRIandMP-MRIshowedasimilarperformanceintermsofoverall

diagnosticaccuracy,withanareaunderthecurveof0.91and0.93,respectively(p=n.s.).

Conclusions:BP-MRIprostateprotocolisfeasibleforprostaticcancerdetectioncomparedtoastandard

MP-MRIprotocol,requiringashorteracquisitionandinterpretationtime,withcomparablediagnostic

accuracytotheconventionalprotocol,withouttheadministrationofgadolinium-basedcontrastagent.

1. Introduction

Prostatecancer(PCa)isoneofthemostcommontypesoftumor

andthesecondhighestcauseofcancer-relatedmortalityinmales

[1].In75%–85%ofcases,PCaoccursintheperipheralzone(PZ);

however,ithasbeenshownthatthetransitionalzone(TZ)harbors

cancerinupto25%ofradicalprostatectomyspecimens[2].Early

diagnosis,targetedtherapyandaccuratemonitoringfollowingthe

radicalprostatectomy havea signiﬁcantimpactonthe

progno-sisofthesepatients.Clinical suspicionofPCais typicallybased

ondigitalrectalexamination(DRE)and/ortheﬁndingofelevated

∗ Correspondingauthorat:DepartmentofAdvancedBiomedicalSciences Univer-sity“FedericoII”,ViaPansini,5,80131,Naples,Italy.

E-mailaddress:mimbriaco@hotmail.com(M.Imbriaco).

prostate-speciﬁcantigen(PSA),andpatientsaretypicallyreferred

forprostatebiopsy,mostcommonlyperformedundertransrectal

ultrasound(TRUS)biopsyguidance[3–5].

Multiparametricmagneticresonanceimaging(MP-MRI)is

cur-rentlyconsideredthemostpromisingimagingmodalitytoevaluate

patientswithsuspicionofPCa,providinghighqualityimagingof

theprostate[6–11].

In2012,theProstateImagingReportingandDataSystem

(PI-RADS)wascreatedtostandardizetheinterpretationandsystematic

reportingof prostateMR imaging[12].Sincetheﬁrst

introduc-tionofPI-RADSversion1bytheEuropeanSocietyofUrogenital

Radiology,researchershaveshowntheclinicalutilityofPI-RADSin

localizingPCa,classifyingtheriskgroups,andimprovingtheyield

oftargetbiopsy[13,14].Morerecently,asimpliﬁedscoresystem

(i.e.PI-RADSv2)hasbeenproposedtocategorizeandsummarize

thelevelsofsuspicionorriskofhavingprostaticcarcinomaand

http://dx.doi.org/10.1016/j.ejrad.2016.10.009

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toreducevariabilityinimaginginterpretations[15].Despitethe

improvementsand usefulnessof PI-RADS v2,controversies still

existinparticularontherealbeneﬁtofcontrastmaterial

adminis-tration[16].Nonetheless,PI-RADSv2suggeststhatallprostateMRI

examinationsshouldincludeadynamiccontrastenhanced(DCE)

sequencefordetectionofPZprostaticlesions[15].

A newmodality for imaging of patientswith PCa hasbeen

recently proposed, based on a biparametric (T2-weighted and

diffusion-weightedimaging_−DWI–)magneticresonanceimaging

(BP-MRI)protocolforPCadetection[16–18].However,tothebest

ofourknowledge,aprospectivestudyaimedtoevaluatethe

diag-nosticaccuracy ofMP-MRI compared totheoneachievedwith

theuseofBP-MRIhasnotyetbeenperformed,sinceallthe

pub-lishedstudiesevaluatedonlythediagnosticaccuracyofBP-MRIin

combinationtoclinicaland/orlaboratoryﬁndings[17,18].

Therefore, the aimof thepresent exploratory study wasto

prospectivelydeterminethediagnosticaccuracyofaBP-MRI

proto-colforthePCadetection,comparedtoastandardMP-MRIprotocol

thatincludedT2-weightedimaging,DWIandDCE,usinga3T

scan-nerandwithouttheuseofanendorectalcoil.

2. Materialandmethods

2.1. Subjects

Fromaninitialgroupof125subjectsadmittedtoourUrology

Department,82untreatedpatients(meanage65±7.6years,age

range:43–84)wereenteredintothisstudy.Inclusioncriteriawas

theclinicalsuspicionofPCa,derivedfromeitherelevatedPSAlevels

orabnormalﬁndingsonDRE.AllpatientsenrolledhadaserumPSA

assessment,DREandﬁnallyunderwentMP-MRIat3T.Withinone

monthfromtheMRIstudyallpatientsunderwentasystematic

12-coreTRUSguidedbiopsy,toestablishaﬁnaldiagnosis.Informed

consent,a requirementoftheprotocolapprovedbythe

Institu-tionalClinicalResearchSubpanelonHumanStudiesatourInstitute,

wasobtainedinallpatients.Patient’sdemographicsandclinical

variablesareshowninTable1.

Table1

Patientsdemographicsandclinicalvariablesofthesubjectsincludedinthestudy.

Allgroup Patientswith positivebiopsy Patientswith negativebiopsy Numberofpatients 82 34 48 Age(mean±SD) 65±7.6 (range43–84) 66±5.3 (range43–84) 63±7.4 (range53–78) PSAlevels(mean±SD) 8.8±8.1 9.9±11.1 8.0±5.0 Prostatevolume (mean±SD) 62.9±28.6 51.0±19.3 72.8±30.8 Tumorsize (mean±SD) n.a. 12.0±6.1 n.a. GleasonScore=6(3+3) ISUPGroup1 n.a. 12 n.a. GleasonScore=7(3+4) ISUPGroup2 n.a. 12 n.a. GleasonScore=7(4+3) ISUPGroup3 n.a. 5 n.a. GleasonScore=8(4+4) ISUPGroup4 n.a. 4 n.a. GleasonScore=9(5+4) ISUPGroup5 n.a. 1 n.a.

PSA=ProstateSpeciﬁcAgent;SD=StandardDeviation;Agesareexpressedinyears; PSAlevelsareexpressedasnanograms/milliliters;Prostatevolumeisexpressed incubiccentimeters;Tumorsizeisexpressedinmillimeter;ISUP=International SocietyofUrologicalPathology.

2.2. MRIacquisitionprotocol

AllMRIscanswereacquiredonthesame3Tscanner

(MAG-NETOM Trio, Siemens Medical Solutions, Erlangen, Germany),

equippedwithasurfacephasedarraycoil(BodyMatrix,Siemens

MedicalSolutions).

Acquisition protocol included for all subjects the following

sequences:T2-weightedturbospinecho(TSE)imagingacquired

withaxial,sagittalandcoronalorientations(repetitiontime[TR],

4000ms;echotime[TE],101ms;ﬁeldofview200×200mm;

thick-ness 3mm, no gap), a DWI-sequence (TR, 4900ms; TE, 89ms;

b-factor0,400,2000;ﬁeldofview200×200mm;thickness3mm,

nogap,axialorientation)anda3Dfastlow-angleshot(FLASH)

T1-weightedspoiledgradient-echosequenceontheaxialplane(TR,

4.91ms;TE,1.74ms,ﬁeldofview200×200mm,thickness3mm,

nogap)toperformmeasurementsinrapidsuccession,immediately

followingcompletionofanintravenousbolusinjectionof0.1ml/kg

gadopentetatedimeglumine,usingapowerinjector(Medtron)at

3ml/sfollowedbya30mlsalineﬂush,54contrast-enhancedsets

of imageswereacquiredsequentially withouta delay between

acquisitions,thereforetimeresolutionwas7s.Allthesesequences

wereevaluatedfortheMP-MRIprotocol.For theBP-MRI

proto-col were evaluated only four sequences extrapolated fromthe

above-mentionedMP-MRIacquisitionprotocol,namelythethree

T2-weightedTSEsequences,alongwiththeDWIsequence.

Asummaryofallthesequencesevaluatedinthisstudy,along

withthecorrespondingacquisitiontimes,isshowninTable2.

2.3. Imageanalysis

Imageswerereviewedseparatelybytworadiologists(M.I.and

A.B.)withrespectively14yearsand10yearsexperienceinprostate

MRimaging.ThetworadiologistsreadindependentlytheBP-MRI

ﬁrst,followedbythefullMP-MRIscans,afteranintervalbetween

20and30days,bothblindedtotheclinicalindicationandtothe

PSAvalues.

MRIcriteriasuggestiveformalignancywerebasedonthe

PI-RADSv2criteria,aspreviouslydescribed[15].Brieﬂy,alldetected

lesionswereclassiﬁedgivingascorefrom1to5,where,1was

con-sideredverylowprobabilityofPCa(clinicallysigniﬁcantprostatic

carcinomawashighlyunlikelytobepresent);2,aslow

probabil-ity(clinicallysigniﬁcantprostaticcarcinomawasunlikely tobe

present);3,asintermediateprobability(thepresenceofclinically

prostaticcarcinomadiseasewasequivocal);4,ashighprobability

(clinicallysigniﬁcantprostaticcarcinomawaslikelytobepresent)

Table2

ComparisonoftheMP-MRIvstheBP-MRIprotocol.

MultiparametricMRprotocol (∼24min)

BiparametricMRprotocol(∼17min) TSET2-weightedsequence,

axialplanes (AT=4‘11“)

TSET2-weightedsequence,axial planes

(AT=4‘11“) TSET2-weightedsequence,

sagittalplanes (AT=3‘46“)

TSET2-weightedsequence,sagittal planes

(AT=3‘46“) TSET2-weightedsequence,

coronalplanes (AT=3‘38“)

TSET2-weightedsequence,coronal planes

(AT=3‘38“) DWIsequence,axialplanes

(AT=6‘28“)

DWIsequence,axialplanes (AT=6‘28“)

Dynamiccontrastenhanced3D T1-weighted

spoiledgradient-echo sequence,axialplanes (AT=6‘30“) AT=AcquisitionTime.

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5,asveryhigh(clinicallysigniﬁcantprostaticcarcinomawashighly

likelytobepresent).

2.4. Prostatebiopsyprocedure

Anurologistwithover10yearsofexperienceinTRUSguided

biopsy performed all the prostate biopsies in the study. All

biopsies were performed with peri-prostatic local anesthetic

(10ml Lidocaine 1%) and pre-procedural antibioticprophylaxis

(Ciproﬂoxacin).UsingaBKultrasoundscanner,endorectalprobe,

aneedleguide,andan18-Gauge25-cmbiopsyneedle.AfterMRI

examination, all patients underwent a standard 12-core TRUS

guidedsextantbiopsy.Biopsieswereobtainedfromeachof6

sagit-talregions(3perside)movingfromprostaticbasetoapexwith2

coresfromeachzoneforatotalof12cores.Inparticular,1-cmin

lengthTRUSbiopsiescoresweretakenfrom12prostaticregions

andmarkedseparately.Othersamplesweretakenfromthe

suspi-ciousareaifclearTRUSlesionswerepresent.Theprocedurewas

welltoleratedinallpatientsincludedinthestudy,withnomajor

complicationsaftertheprocedure. Allbiopsysamplesweresent

tothepathology laboratoryof ourinstitution,where theywere

analyzedand reportedaccordingtotheInternationalSocietyof

UrologicalPathology(ISUP)2005modiﬁedGleasonscoregrading

system[19].

2.5. Statisticalanalysis

ForeachprostateMRimagingprotocol,thediagnostic

perfor-mancewasassessedbymeasuringtheareaunderthecurve(AUC)of

thefree-responsereceiveroperatingcharacteristicanalysis(ROC)

[20].Diagnosticaccuracy,sensitivity,speciﬁcity,with

correspond-ing 95% conﬁdence intervals, were determined and compared

betweentheMP-MRIandtheBP-MRI.ThedifferencesintheAUC

werestatisticallyanalyzedusingtheChi-squaredtest.Inparticular,

wetestedwhethertherewasastatisticallysigniﬁcantdifference

betweenresultsprovided bythetwo MR imagingprotocols, as

conﬁrmedbythereferencestandards.The␬statisticswerealso

performedto assess theinter-readeragreement. Thedegree of

inter-readeragreementwasinterpretedwiththefollowinginterval

of␬values:0–0.20=poor,0.21–0.40=fair,0.41–0.60=moderate,

0.61–0.80=good,and 0.81–1=excellentagreement.All analyses

were performedwith the Statistical Package for Social Science

(SPSS)(SPSSInc,v.17.0,Chicago,Ill).Ap-valuelowerthan0.05

wasconsideredasstatisticallysigniﬁcant.

3. Results

ThemeanPSAlevelofallsubjectsincludedinthestudywas

8.8±8.1ng/ml.Atotalof 34PCawereidentiﬁedin82 patients.

Amongthese,29patientsprovedtohaveaPCaofthePZ,whilein

5patientsPCawasidentiﬁedasbelongingtotheTZ.

AssuggestedbythePI-RADSv2[15],forthe29patientswithPCa

ofthePZ,averagedimensionofthetumorwasmeasuredonaxial

planeontheADCmap,anditprovedtobe12mm(rangingfrom

5to24mm).Ontheotherhand,the5patientswithPCaoftheTZ

showedanaveragedimensionofthetumorof20mm(rangingfrom

10to31mm),measuredonaxialplaneontheT2-weightedimages,

slightlyhighercomparedtotheonemeasuredontheimagesofPZ

patients.

Meanvolumetricvalueoftheentireglandofpatientswith

pos-itivebiopsywas51.0ml(rangingfrom25to90ml),measuredas:

(axialdiameter×sagittaldiameter×coronaldiameter)×0.52

When considering theoverall diagnosticaccuracy,

indepen-dentlyfromthezonalanatomy,thetworeadersassignedaPI-RADS

scorediscordantinsevencases(allintheassignmentofascoreof1

ratherthan2,andviceversa).Theinter-readeragreementbyusing

quadratic␬coefﬁcientsprovedtobeexcellent(␬=0.866).

TheAUCobtainedfromtheROCanalysiswere0.91and0.93for

BP-MRIandMP-MRI,respectively(p=n.s.).Inparticular,the

BP-MRIanalysisdemonstratedanoveralldiagnosticaccuracyof92.7%

(76/82cases)inthedetectionofPCa,withasensitivityof85.3%

(29/34cases)andaspeciﬁcityof98.1%(52/53cases).Similarly,the

MP-MRIanalysisprovedanoverallaccuracyof93.9%(77/82cases),

withasensitivityof91.1%(31/34cases)andaspeciﬁcityof96.2%

(51/53cases).

Wethenmovedtocomparethediagnosticaccuracyofthetwo

approacheswithregardtothezonalanatomy.ForthePCaofthe

PZ,theAUCobtainedfromtheROCanalysiswere0.90and0.92for

BP-MRIandMP-MRI,respectively(p=n.s.).Inparticular,the

BP-MRIanalysisdemonstratedadiagnosticaccuracyof92.2%(71/77

cases)inthedetectionofPCaofthePZ,withasensitivityof82.8%

(24/29cases)andaspeciﬁcityof97.9%(47/48cases).Similarly,the

MP-MRIanalysisprovedanoverallaccuracyof93.5%(72/77cases),

withasensitivityof89.7%(26/29cases)andaspeciﬁcityof95.8%

(46/48cases).

In particular,MP-MRI showeda slighter,but not signiﬁcant,

betterperformancewhenidentifyingthetruepositive,by

iden-tifying26outof29patientswithPCa,comparedtothe24outof

29oftheBP-MRI.Indeed,accordingtoBP-MRIinthreecasesitwas

assignedaPI-RADSscoreof3,whichwaslatermodiﬁedto4after

theadditionalevaluationofDCEsequencesinMP-MRI,leadingto

theidentiﬁcationoftwomoretruepositive,withanadditionalfalse

positive.

Finally,for thediagnosticaccuracyof PCaof theTZ, BP-MRI

andMP-MRIshowedanidenticalperformanceboth intermsof

sensitivityandspeciﬁcity,correctlyclassifyingallofthelesions.

Alldifferencesintermsofdiagnosticaccuracyprovedtobe

sta-tisticallynotdifferentattheChi-squaredtest.

Table3showstheoveralldiagnosticperformanceofMP-MRI

comparedtoBP-MRIinthetotalnumberofpatientsincludedin

thestudy,whileFigs.1and2showtwoexamplesofPCs.

AfterTRUSbiopsy,12/34 (35.3%)patientsunderwent radical

prostatectomy,thatconﬁrmedthediagnosis.

4. Discussion

Inthisexploratorystudywehaveshownfortheﬁrsttimethe

clinicalfeasibilityandthesimilardiagnosticaccuracyofaBP-MRI

protocolcomparedtoaMP-MRIprotocolforthedetectionofPCaby

usinganhighﬁeld3TMRscanner,withouttheuseofanendorectal

coil,inabiopsy-naïvepatientpopulation.

MP-MRI of the prostate consisting of both anatomic

T1-weightedandT2-weightedMRI sequencesas wellasfunctional

Table3

Overalldiagnosticaccuracy,sensitivities,speciﬁcitiesandareasunderthecurveforMP-MRIandBP-MRIprotocol.

Overalldiagnosticaccuracy Sensitivity Speciﬁcity AUC

BP-MRI 92.7% (76/82) 85.3%(29/34) 98.1%(52/53) 0.91

MP-MRI 93.9% (77/82) 91.1%(31/34) 96.2%(51/53) 0.93

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Fig.1.Imagesina58yearsoldpatientwithprostaticadenocarcinomaoftheleftperipheralzone(Gleasonscore7,4+3−ISUPGroup3).

A:T2-weightedaxialimage;B:diffusion-weightedimage,alongwiththecorrespondingADCmap(C)showingafocalhypointenselesionof7mmofdiameter,characterized bydiffusionrestriction(arrows).D:dynamiccontrastenhancementimageshowsthesamefocalareaofearlyenhancement(arrow).ThePI-RADSscoreofdynamiccontrast enhancementimagingwaspositiveaccordingtobothreaders.Nonetheless,thescoreassignedbybothreadersonthediffusion-weightedimagewas4,sothatthedynamic contrastenhancementdidnotchangetheoverallPI-RADSscoreof4,whichwassuggestiveofahighprobabilityofclinicallysigniﬁcantcancer.

Fig.2.Imagesina65yearsoldpatientwithprostaticadenocarcinomaoftheleftperipheralzone(Gleasonscore7,3+4−ISUPGroup2).

A:T2-weightedaxialimage;B:diffusion-weightedimage,alongwiththecorrespondingADCmap(C)showingafocalhypointenselesionof10mmofdiameter,characterized bydiffusionrestriction(arrows).D:dynamiccontrastenhancementimageshowsablurrier,largerfocalareaofenhancement,lesscircumscribedthantheonevisibleonthe ADCmap(arrow).SimilarlytowhatshowninFig.1,thePI-RADSscoreofdynamiccontrastenhancementimagingwaspositiveaccordingtobothreaders.However,thescore assignedbybothreadersonthediffusion-weightedimagewas4,sothatthedynamiccontrastenhancementdidnotchangetheoverallPI-RADSscoreof4.

sequences,includingDWIMRIandDCEsequenceshasbeen

pro-posedasthemethodofchoicetoimagepatientswithsuspicionof

prostaticcarcinoma[6,7,11].ThisMP-MRItechniqueisableto

pro-videvaluableinformationinavarietyofclinicalsettings[21–23].

Furthermore,endorectalcoilsatboth1.5Tand3Tscanner,have

beenshowntoimproveprostate MR imagequalityand staging

performancecompared with thoseof pelvic phased-arraycoils,

althoughthenecessityofanendorectalcoilat3Tisstill

question-ableandunderdebate[23,24].

AlthoughMP-MRI is considered the technique of choice for

studyingpatientswithsuspicion ofPCa,this approach isprone

todifferentproblems,mainlyaccountabletotheuseofcontrast

agents.Indeed,itisknownhowgadolinium-basedcontrastagents

arerelativelyexpensive,thereforeaddingsigniﬁcantcoststothe

healthcare system; furthermore, recent evidences suggest that

theirusecouldleadtopossibleaccumulationindeepcerebral

struc-tures,suchasdentatenuclei[25,26].

Forallthisreasons,severalgroupsinthepastfewyearshave

suggested todevelop a more feasible, simple and less invasive

imagingmethodforidentifyingPCa.Inparticular,inarecentpaper,

Rais-Bahramiandcolleaguesshowedtheusefulnessofusingonly

T2-weightedand DWIimagesinthedetection ofPCa [18].The

authors showed that when a BP-MRI wascombined withPSA

levelandPSAdensity,evenhighersensitivityandspeciﬁcitywere

achieved,providinggreaterdiagnosticaccuracyindetecting

clin-icallysigniﬁcantdisease.Thesedataprovidesupportforalimited

non-contrastMRIasapotentialadjuncttooltooptimizePCa

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BP-MRIprotocolalongwiththeuseofPSAorPSAdensity,in a

biopsy-naivecohortof59patientsatriskforPCa.Theauthors

con-cludedthatthecombineduseofaBP-MRI,PSA,andPSAdensity

resultsinimproveddiagnosticaccuracyfordetectingclinically

sig-niﬁcantprostaticcarcinoma[17].

Furthermore, in December 2014, a joint steering

commit-teeoftheAmericanCollegeof Radiology,ESUR,andAdMeTech

Foundation agreed to collaborate on the development of an

improvedPI-RADSv2.ThePI-RADSv2hasbeenofﬁciallyreleased

inDecember2014[15],withthespeciﬁcaims ofPI-RADSv2to

establishsimpliﬁedguidelinesforminimumacceptabletechnical

parametersforprostateMP-MRI,inordertodevelopassessment

categoriesthatsummarizethelevelsofsuspicionorriskofhaving

prostaticcarcinomaandtoreducevariabilityinimaging

interpre-tations[15].Tosummarize,accordingtoPI-RADSv2,forevaluation

oflesionsofPZ,DWIisthedominantsequence,whilefortheTZthe

T2-weightedsequenceplaysaprimaryrole.Consequently,a

sec-ondaryrolehasbeenassignedtoDCEsequence,withitsapplication

solelyconducibleinprovidingadditionalinformationincasesofa

PZlesionwithascoreof3.Therefore,DCE imagingplaysarole

astheminorsequencewhenPZcancerisequivocallysuspectedat

DWIimaging[15].

Thesesimpliﬁedinterpretationcriteriaforpatientswith

suspi-cionofPCacorroboratetheﬁndingsofourmanuscript.Indeed,we

havedemonstratedthefeasibilityofaBP-MRIprotocolasa

pow-erfuldiagnostictoolfordetectionofPCacomparedtotheMP-MRI

protocol.Inparticular,wespeculatethatourresultscould

repre-sentafurtherimprovementofPI-RADSv2.Here,wedemonstrated

howthesoleevaluationoftwoparameterswassufﬁcientinour

populationforanaccuratedetectionofPCa,inparticularofthePZ,

comparedtotheevaluationoftheentireMP-MRIprotocol.Indeed,

theroleofDCEhasalreadybeenlimitedbythecurrentPI-RADSv2

tothedetectionofdoubtfulPCaofthePZ,withnoindicationsinthe

detectionoflesionsoftheTZ[15].Asaconsequence,ourresults

allowustohypothesizethefutureeliminationofcontrastagent

administrationintheradiologicalsuspicionofPCa,withobvious

advantagesforbothpatientsandhealthcaresystems.Inaddition,

itshouldbenotedthatthetotalacquisitiontimefortheBP-MRI

protocolwas∼17min,comparedto∼24minforMP-MRIstandard

protocol,withaslightreductioninthetotalacquisitiontimeand

patientpreparationforMRexamination.Nevertheless,a further

reductionincostsandpatientdiscomfortwasobtainedwithoutthe

useofanendorectalcoil,withoutachievingasigniﬁcantlossinthe

overalldiagnosticaccuracy,duethehighﬁeldoftheMRscanner.

Weacknowledgeseverallimitationsinthepresentstudy,ﬁrstly

relatedtotherelativelylimitedsamplesizeofourgroupofpatients.

Weare awarethatsucha smallsample,especially ifcompared

tootherpreviousworks [27,28],couldlead toa

misinterpreta-tionand/oroverestimation ofourdata.In particular,this small

samplesizecouldbesomehowresponsiblefortheextremely

ele-vateddiagnosticaccuracyofPCaoftheTZ.However,itshouldbe

notedthatPCaoftheTZareknowntobelesscommonthanthe

onesaffectingthePZ[21],andthatthesepatientsusuallyshowan

highertumorsizecomparedtopatientswithPCaofthePZ[21],

withourresultsbeinginagreementwiththesepreviousﬁndings.

Nonetheless,forallthisreasonsfutureinvestigationsina larger

patientpopulationarewarrantedtovalidatetheﬁndingsofthis

exploratorymanuscript.

Anotherlimitationthatshouldbeconsideredisthatthegold

standard in our series was 12-core biopsy rather than radical

prostatectomythatwasperformedonlyin12outof34patients

(35.3%);howeverintheclinicalpracticeTRUSbiopsyisusually

rec-ommendedastheﬁrstlinediagnosticprocedureinpatientswith

suspicionofprostaticcancer,withalltheknownlimitations[7,11].

Inconclusion,wesupportedthehypothesisthataBP-MRI

pro-tocolforthestudyoftheprostate,performedat3Twithouttheuse

ofanendorectalcoilortheadministrationofcontrastagent,isa

feasibletoolforthePCadetection,especiallyofthePZ,compared

to a standard MP-MRI protocol, requiring a shorter acquisition

andinterpretationtimeandwithcomparablediagnosticaccuracy.

TheimplementationandvalidationofaBP-MRIprotocolinlarger

patientpopulationcouldfurthersimplifythePI-RADSv2scoring

system,improvingthestandardizationofprostateMRimage

inter-pretationandforabetterstratiﬁcationofpatientswithsuspicion

ofprostaticcancer.

Conﬂictofinterest

Allauthorsdo not haveany ﬁnancialand personal

relation-shipswithotherpeopleororganizationsthatcouldinappropriately

inﬂuence(bias)ourwork.

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