【医学英文课件】-Image-Guided-Therapy-for-Prostate-Cancer-

RafaelSanchez-Salas,MDDepartmentofUrologyL’InstituteMutualisteMontsourisParis,France

Image-GuidedTherapyforProstateCancer:Thefocalapproach

DisclosuresOlympus,EDAP-TMS,HistoScanning,IntuitiveEcoleEuropéendeChirurgie;Paris,FranceAgendaImage-GuidedTherapyinUrologyDiagnosisofProstateCancerandSelectionforFocalTherapyImaginginLocalizedProstateCancerProstaticBiopsies:AvailableTechniquesandApproachesAvailableAblationEnergiestoTreatProstateCancerSurveillanceAfterFocalTherapySummary

Image-guidedTherapyforProstateCancer:

QuoVadis?

UrologyandtechnologyImagingandablativestechniquesStagemigrationandriskstratificationImage-guidedTherapyforProstateCancerFOCALTHERAPYRadicalOptionsActiveSurveillanceAleaiactaestFocalTherapyforPCa:

LevelofEvidenceofCurrentRecommendations

forCommonPracticeAgendaImage-GuidedTherapiesDiagnosisofProstateCancerandSelectionforFocalTherapyImaginginLocalizedProstateCancerProstaticBiopsies:AvailableTechniquesandApproachesAvailableAblationEnergiestoTreatProstateCancerSurveillanceAfterFocalTherapySummary

DiagnosisofProstateCancerandSelection

forFocalTherapy

PSAPCA3proPSACanceraggressivenessandvolume?Selectionforfocaltherapy?PSAselection:Before2010,low-riskPCapatientswereconsideredforFT.ThereforePSA<10ng/mL

delaRosetteetal.,JEndourol.2010Morerecently,extensiontointermediaterisk.MostpreferPSA<15ng/mL

vandenBos,etal.EurUrol.2014Walzetal,SIU-ICUD2015

DiagnosisofProstateCancerandSelection

forFocalTherapy

Overallcharacteristicsofpatientsincludedincurrentlypublishedandongoingtrialsonfocaltherapyintheprimarysetting:56%low-riskdisease36%intermediate-riskdisease8%high-riskdiseaseMeanPSA:3.76–24ng/mLMedianage:56.5–73yrsValerioM,etal.EurUrol2015FOCALTHERAPY:INDICATIONSAge&LifeExpectancyNoagethresholdLifeexpectancy>10yrsRiskIntermediaterisk(GS3+3,3+4)ProstateVolumeNolongeranissueTumorVolumeNoconsensusregardingaminimumtumorvolumeforFTTumorFocalityMultifocalcancershouldnotprecludefocaltherapyReportsfromExpertConsensusMeetingsvandenBosetal.,EurUrol.2014Donaldsonetal.,EurUrol.2015Ahmedetal.,BJUInt.2012Algabaetal.,JEndourol.2010AlternativestoFocalTherapyActivesurveillanceSurgeryRadiotherapyTheIndexlesion.Themonoclonaloriginofmetastaticprostatecancer.?56patientstreatedwithHIFU–indexlesionablationAt12mo:-80.8%patientshadhistologicalabsenceofclinicallysignificantcancer

85.7%hadnomeasurablePCa(biopsyand/ormpMRI)-3.6%patientshadclinicallysignificantdiseaseinuntreatedareasnotdetectedatbaselineAhmedH,etal.

EurUrol.2016FocalAblationTargetedtotheIndexLesioninMultifocalLocalisedProstateCancer:aProspectiveDevelopmentStudyAgendaImage-GuidedTherapiesDiagnosisofProstateCancerandSelectionforFocalTherapyImaginginLocalizedProstateCancerProstaticBiopsies:AvailableTechniquesandApproachesAvailableAblationEnergiestoTreatProstateCancerSurveillanceAfterFocalTherapySummarydeRooijM,etal.AJRAmJRoentgenol.2014 Hambrock,etal.Radiology.2011Increasessignificantcancerdetection.HighNegativePredictiveValuesinMRIaccuracystudies.ImaginginLocalizedProstateCancer:mpMRI526patients—Thepooleddatashowedaspecificityof0.88(95%CI,0.82–0.92)andsensitivityof0.74(95%CI,0.66–0.81)forprostatecancerdetection.deRooijM,etal.AJRAmJRoentgenol.2014AccuracyofMultiparametricMRIforProstateCancerDetection:AMeta-AnalysismpMRIisthe

optimalapproachforfocaltherapy.

High-qualitymachine(3Twith/withoutendorectalcoilor1.5Twithendorectalcoil)Judgedbyanexperiencedradiologist.mpMRIhassufficientpotentialtodetectalesionof~0.5mLwithsensitivityaswellasspecificityof~90%.MullerBG,etal.BJUInt.2014TheRoleofMagneticResonanceImaging(MRI)inFocalTherapyforProstateCancer:RecommendationsfromaConsensusPanel.

ImaginginLocalizedProstateCancer:mpUS

GrayScaleDopplerImagingContrast-enhancedUltrasoundHistoscanningElastographyLookingintothefutureMullerBG,etal.CurrOpinUrol.2014Real-timeelastographydetectedprostatecancerwith49%sensitivityand73.6%specificity.ItwouldsuggestthattheHSprotocolrequiresfurtherrefinementbeforeclinicalimplementation.Themultiparametricapproachdecreasedthefalse-positivevalueofreal-timeelastographyalonefrom34.9%to10.3%andimprovedthepositivepredictivevalueofcancerdetectionfrom65.1%to89.7%.BrockM,etal.JUrol.2013100patientswithbiopsy-provenPCaunderwentpre-operativeTRmpUScombiningreal-timeelastographyandcontrast-enhancedultrasound.MultiparametricUltrasoundoftheProstate:AddingContrastEnhancedUltrasoundtoReal-TimeElastographytoDetectHistopathologicallyConfirmedCancerImaginginLocalizedProstateCancer:mpUSCombineddataonsensitivityandspecificityofthedifferentUSmodalitiesMullerBG,etal.CurrOpinUrol.2014CombinedPET/MRImayprovideadequatetissuecontrastandhelptoenhancetheclinicalassesmentofpatientswithMRIinvisiblePCaParkHetal,JNuclMed.2012ImaginginLocalizedProstateCancer:

CombinedimagingBarretetalSIU-ICUD2015AgendaImage-GuidedTherapiesDiagnosisofProstateCancerandSelectionforFocalTherapyImaginginLocalizedProstateCancerProstaticBiopsies:AvailableTechniquesandApproachesAvailableAblationEnergiestoTreatProstateCancerSurveillanceAfterFocalTherapySummary

ProstaticBiopsies:

AvailableTechniquesandApproaches

Standard12-coreTRUSbiopsy

Cancerdetectionrate:44%Finalspecimenanalysis:30–40%ofthepatientswereupgradedfromtheirinitialbiopsy.Greaterextracapsulardisease.Seminal-vesicleinvolvement.Lymph-nodeinvolvement.Positivemarginratescomparedwiththosewhowerenotupgraded.ClinicaldecisionmakingandchoosingtherighttreatmentTilki,etal.UrolOncol.2011Multi-parametricMRI–targetedbiopsyTransperinealmappingtemplateprostatebiopsySystematictrans-rectalbiopsyProstaticBiopsies:

AvailableTechniquesandApproachesCombinedFTBandSBdetected97%ofallsignificantPCa(sPCa)lesionsandwassuperiortompMRI(85%),FTB(79%),andSB(88%)alone(p<0.001each).120patientssubmittedtompMRI+Fusion-targetedbiopsy(FTB)+Saturationbiopsy(SB).Allofthemwerethentreatedwithradicalprostatectomy(RP).RadtkeJP,etal.EurUrol.2016FTBdiagnosed30%morehigh-riskcancers.FTBcombinedwithSBledtoanadditionaldiagnosisof22%ofmostlylow-riskcancers.ThepredictiveaccuracyofFTBindifferentiatinglow-vs.intermediate-vs.high-riskcancerswasgreaterthanSB.1,003mensubmittedtompMRI+Fusion-targetedbiopsy(FTB)+standardbiopsy(SB).170werethentreatedwithRP.SiddiquiMM,etal.JAMA.2015

ProstaticBiopsies:

AvailableTechniquesandApproaches

MRI-TRUS–guidedfusion-targetedbiopsyIncreaseddetectionofhigh-riskPCa.Decreaseddetectionoflow-riskPCa.Anteriortumorsdetection.

Baco,etal.EurUrol.2015Mozer,etal.BJUInt.2015Siddiqui,etal.JAMA.2015SamplingefficiencywasinfavorofMRIfusionbiopsywith46.0%oftargetedbiopsyvs.7.5%ofsystematicTPMdetectingGleasonscore7orgreatercancers.Todiagnose1Gleasonscore7orgreatercancer,3.4targetedand7.4systematicbiopsieswereneeded.294patientssubmittedtompMRI+TPM.Allpatientshadsystematicbiopsies+fusion-targetedcores.RadtkeJP,etal.JUrol.2015AgendaImage-GuidedTherapiesDiagnosisofProstateCancerandSelectionforFocalTherapyImaginginLocalizedProstateCancerProstaticBiopsies:AvailableTechniquesandApproachesAvailableAblationEnergiestoTreatProstateCancerSurveillanceAfterFocalTherapySummaryHEATEFFECTFREEZINGEFFECTELECTRICEFFECTRADIATIONPHOTOSENSITIZERCryotherapyHIFULASERMicrowavethermotherapyRadiofrequencyablationNanoparticlesthermotherapyEBRwithmicroboostBrachytherapyProtontherapyCyberknifePhotodynamictherapyElectroporationJácome-PitaFX,etal.,Ecancermedicalscience.2014;8:435.DelaRosetteetal.SIU-ICUD2015AvailableAblationEnergiesIdealEnergy:DefinitionTRIFECTAEffectivemechanismRe-doableMorbidityProstateanatomyCostandavailabilityEasyapplicationToeradicateknowncancerTopreserveuninvolvedtissueTopreservegenitourinaryfunctionDelaRosetteetal,SIU-ICUD2015ClinicalResultsCRYOTHERAPYHIFUFollow-up15–70months1–10yearsBiopsyrecurrence(treatedside)4%1–10%Potency65–90%95%Continence95–100%90–100%BDFS(nadir+2ng/mL)forlowandintermediateriskAround80%65–75%ComplicationsUrinaryretention,RectalfistulaHematuria,Dysuria,RectalpainandtearMarien

A,etal.UrolOncol.2014IRE—ProspectiveStudiesMulticenterphaseI-IItrial16patientstreatedwithIREwithoutcurativeintentFirstresultsonhisto-pathologicoutcomesofIRE:-Noviabletissuewasseenwithintheablationzone.Fibrinoidnecrosisoftheneurovascularbundlewasobservedin13patients.Denudationoftheurotheliumoftheprostaticurethrain9patients.vanderBosW,etal.JUrol.2016ValerioM,etal.EAUMunich2016Single-centerprospectiveNEATtrial20patientstreatedwithIREIREconferslow-riskofgenitourinarytoxicitiy.MedianPSAsignificantlydroppedto1.7ng/mL.NoresidualcancerfoundatMR-targetedbiopsyin61.1%.2patientsdeservedfurthertreatment(RPandfocalHIFU).TOOKAD®—PhaseIIITrial120ptsrandomizedtoVTPvs.250randomizedtoAS-PSA≤10-1–3positivecoresand≤5mmCCLGS3+3cTuptocT2aVTPASCancerprogression28%58%Ptsunderwentradicaltherapy6%29%Ptswithnegativebiopsiesat24mos49%14%-NodifferenceintermsofIPSSandIIEF.-SlightlyhigherGrade2complicationsinVTPgroup.EmbertonM.EAUMunich2016

“AlaCarte”ModelSivaramanA,BarretE.EurUrol.2016AgendaImage-GuidedTherapiesDiagnosisofProstateCancerandSelectionforFocalTherapyImaginginLocalizedProstateCancerProstaticBiopsies:AvailableTechniquesandApproachesAvailableAblationEnergiestoTreatProstateCancerSurveillanceAfterFocalTherapySummaryFollow-uplength—minimum5yearsModalitiestoinclude—mpMRI+biopsies+assessmentofEF,QoL,LUTS,UCPSAevery3mosinthefirstyearandevery6mosthereaftermpMRIat6mosand1yrandeveryyearthereafter12-core+TRUSbiopsycombinedwithtargetedbiopsy(MRIfusion)at1yrandthereafterifsuspiciononimagingMullerBG,etal.WorldJUrol2015Follow-upModalitiesinFocalTherapyforProstateCancer:ResultsfromaDelphiConsensusProjectSurveillanceAfterFocalTherapy:

PSA,Derivatives,andotherMolecularMarkersThereiscurrentlynotenoughdatadescribingthecourseofserumPSApost-focaltherapywithlong-termprognosis:Recommendation:Recordpost-treatmentPSAlevelsincludingdensity,nadir,andotherkineticsforfutureresearchpurposes.Follow-up:RoleofmpMRIUsefulformonitoringbothtreatedanduntreatedzonesafterfocaltherapy.Minimumrequirements:3TmpMRI1.5TmpMRI+endorectalcoilFollow-uptimes:FirstmpMRIat6–12monthsaftertreatmentOptimalfrequency—notknown.Shouldbedeterminedbypatientfactorsandresourceavailability.

Likelythatinpatientswithlowrisk,imagingcanbeinfrequent.PositivempMRIshouldleadtotargetedbiopsy.Polasciketal,SIU-ICUD2015RoleofBiopsy:Mandatoryrecommendations:mpMRIshouldbepartofanyfocaltherapyprogramandshouldtriggertargetedbiopsyifsuspicious.LittlepublisheddatatoinformoptimalFUbxregimen.mpMRI+possiblefusionbiopsySystematicbiopsyTreatedareaMandatorybiopsyat3–6monthswith4–6cores12–24monthsandagainat5years-Untreatedarea12–24monthsandagainat5years12–24monthsandagainat5yearsMullerGB,etal.WorldJUrol.2015ValerioM,etal.EurUrol.2015

Success/FailureintheTreatedZone

Immediateortechnicalablativesuccess:dependsontheoperator’sassessment.Intermediate-tolong-termsuccess:eradicationofallaggressiveorclinicallysignificantdisease.

DefinitionofsuccessandfailurewithinthetreatedzoneSignificantvolume(≥0.2ccor7mmdiameter)GS3+4(PrognosticGradeGr2)NORESIDUALCANCERSmallvolumeGS3+3Verysmallvolume(<0.2ccor<7mmindiameter)GS3+4SuccessFailurePolasciketal,SIU-ICUD2015:

Success/FailureintheUntreatedZone

Low-riskdiseaseintheuntreatedzoneshouldbemonitoredwithstandardofcareASprotocols.DefinitionofFailure

intheUntreatedZoneDevelopmentofanyfociofclinicallysignificantcancerrequiringfurthertherapy(focidevelopedwithin12–18months—probablyselectionfailure)Polasciketal,SIU-ICUD2015AgendaImage-GuidedTherapiesDiagnosisofProstateCancerandSelectionforFocalTherapyImaginginLocalizedProstateCancerProstaticBiopsies:AvailableTechniquesandApproachesAvailableAblationEnergiestoTreatProstateCancerSurveillanceAfterFocalTherapySummarySummaryImprovedimaginghasdrasticallychangedthePCapathwayDiagnosisTreatmentdecisionandplanningOutcomescontrolFocaltherapytrialsareattheearlystageofclinicaldevelopmentThemajorityofevidenceoncommonpracticeforfocaltherapycomesfromexperts’consensusopinion(LE4)

Whatisstillneededtomakefocaltherapyanacceptedsegmentofstandardtherapy?Solidac