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ComparingTreatmentResultsOf PROSTATECANCER ProstateCancerResultsStudyGroup UpdatedJanuary2017 ProstateCancerTreatmentResearchFoundation 2/11/17 1 ¡ Problem:Patients,physiciansandprovidersneed simple,unbiaseddatabywhichtocomparethe effectivenessofmodernprostatecancer treatmentmethods.Themosteffective treatmentsarethoseinwhichthepatient remainsProstateCancerFree® fortheirlifetime. 2/11/17 2 ¡ § § § § § § ¡ 2/11/17 TheStudyGroupisanassemblyofinternationalexperts fromkeytreatingdisciplines: Surgery(RP&Robotic) ExternalBeamRadiationTherapy(EBRT) Brachytherapy(Seeds) HighFrequencyUltrasound(HIFU) ProtonTherapy(Protons) Cryotherapy(Cryo) Thepurposeofthisworkistoreviewallofthecurrent literatureonprostatecancertreatmentandprovide resultstopatientsandtheirphysicians. 3 ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ Ignace Billiet, MD, F.E.B.U.-Urologist, AZ Groeninge Teaching Hospital, Kortrijk, Belgium David Bostwick, MD, Bostwick Laboratories, Orlando, FL Luis Campos-Pinheiro, MD, Univ. of Lisbon, Lisbon, Portugal David Crawford, MD, Univ. Colorado, Denver, CO Brian Davis, MD, Mayo Clinic, Rochester, MN D. Jeffrey Demanes, MD, UCLA Medical Center, Santa Monica, CA Adam Dicker, MD, Thomas Jefferson U., Philadelphia, PA Steven Frank, MD, MD Andersen, Houston, TX Peter Grimm, DO, Prostate Cancer Center of Seattle, Seattle, WA (Founder, deceased Feb. 20, 2016) Gustavo Guimaraes, MD, AC Camargo Cancer Center, São Paulo, Brazil R. Alex Hsi, MD, Peninsula Cancer Center, Poulsbo, WA Jos Immerzeel, MD, De Prostaat Kliniek, Netherlands Mira Keyes, MD, BC Cancer Agency, Vancouver BC, Canada Patrick Kupelian, MD, UCLA Med Center, Los Angeles, CA Steven Kurtzman, MD, Western Radiation Oncology, San Francisco, CA Stephen Langley, MD, St Luke's Cancer Centre, Guildford, England W. Robert Lee, MD, Duke University Medical Center, Durham, NC Stefan Machtens, MD, Marien-Krankenhaus Hospital, Bergisch-Gladbach, Germany 2/11/17 4 ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ ¡ Alvaro Martinez, MD, William Beaumont , Royal Oak, MI Gregory Merrick, MD, Schiffler Cancer Center, Wheeling, WV Jeremy Millar, MD, Alfred Health Medical Center & Monash University, Melbourne, Australia Brian Moran, MD, Chicago Prostate Institute, Chicago, IL Peter F. Orio, DO, Dana-Farber/Brigham & Women’s Cancer Centers, Boston, MA Antonio Cassio Pellizzon, MD, Camargo Cancer Center, São Paulo, Brazil Bradley R. Prestidge, MD, MS, Bon Secours Cancer Institute, Norfolk, VA Thomas Pugh, MD, University of Colorado School of Medicine, Denver, CO Mack Roach, MD, UC San Francisco, San Francisco, CA Mark Scholz, MD, Prostate Cancer Research Institute, Marina del Ray, CA Katsuto Shinohara, MD, UC San Francisco, San Francisco, CA Janusz Skowronek, MD, Greater Poland Cancer Center, Poznań, Poland Richard Stock, MD, Mt. Sinai, New York, NY Frank Sullivan, MD, College of Medicine, Nursing and Health Sciences, NUI, Galway, Ireland Jehan Titus, MD, Calvary Hospital, St Josephs Collage, Adelaide, Australia Robyn Vera, DO, Radiant Oncology, Lacey, WA Edward Weber, MD, Prostate Cancer Center of Seattle, Seattle, WA Michael Zelefsky, MD, Memorial Sloan Kettering, New York, NY Anthony Zietman, MD, Harvard Joint Center, Boston, MA 2/11/17 5 AboutThisReviewStudy ¡ +48,700prostatearticleswerepublishedbetween 2000andJune2016. ¡ 1,502ofthosearticlesfeaturedtreatmentresults. ¡ 223articleshavemetPCRSGcriteriatobeincluded inthisreviewstudy. ¡ Sometreatmentmethodsareunder-represented duetofailuretomeetcriteria. 2/11/17 6 ¡ ¡ ¡ ¡ ¡ “WillIbecured?”or“Willmytreatmentmakemecancer free?”arevalidpatientquestions. TheindicatorofbeingProstateCancerFree®isalowPSA levelwhichdoesnotrise. Fivetotenyearsaftertreatment,alowPSAlevel indicatescanceriscontrolledandthereisahighlikelihood thecancerwillnotreturn. Resultsgreaterthanfiveyearsarenecessarytobeableto comparetreatmentresults. SuccessisdefinedasPSAatalowlevelandnotrising duringthelifetimeofapatient“ProstateCancerFree®.” 2/11/17 7 ¡ ¡ ¡ ¡ Afterprostatesurgery,PSAnumbersusuallyfallrapidlyto verylownumbersandstaylow. Afterradiation,PSAnumbersusuallycomedownslower, andmayincreasebriefly,thensubsequentlyfall(thisis calleda“PSABump.”) ThesedifferentPSAexpectationsresultindissimilarways toreviewaman’sPSAhistorytojudgetreatmentsuccess. AconsistentriseinPSAafterfiveyearsisgenerally consideredatreatmentfailure. 2/11/17 8 Brachy=SeedImplantation(Brachytherapy,either permanentortemporaryseeds) EBRT=ExternalBeamRadiationTherapy(includes IMRT=IntensityModulatedRadiationTherapy) RP=StandardOpenRadicalProstatectomy RobotRP=RoboticRadicalProstatectomy HIFU=HighIntensityFocusedUltrasound Cryo=Cryotherapy Protons=formofExternalRadiationusingProtons ADT=HormoneTherapy 2/11/17 9 ¡ ¡ ¡ Theexpertpanelagreedunanimouslyonthecriteriaan articlehastomeettobeacceptedforcomparison purposes. EveryProstateCancerarticlewrittenbetween2000and June2016wasreviewed.Firsttodetermineifitwasa treatmentarticle,andsecondlyifitmettheexpertpanel's inclusioncriteria. Theresultsoftheacceptedtreatmentarticleswere plottedtogetheraccordingtoeachriskgroup’s“Prostate CancerFree®”status(intheprofessionalliteraturethisis knownasPSAProgressionFreestatus,meaningno evidenceofarisingPSA.) 2/11/17 10 ¡ Allarticleevaluationsandgraphplottingsarereviewedby theArticleReviewCommitteeandthensubmittedtothe ExpertPanelforconfirmationpriortoallstudyupdates. ¡ Alldatarecipients,includingpatientsandphysicians,are invitedtocritiquethedataandsubmitarticlesforthe PCRSGreviewprocess. 2/11/17 11 CriteriaforInclusionofArticle* 1. ArticlesmustbepublishedinaMajorMedicalJournal. 2. PatientsshouldbeseparatedintoLow-,Intermediate-,and High-RiskGroups. 3. SuccessmustbedeterminedbyPSAanalysis. 4. Allmajortreatmenttypesconsidered:Seeds(Brachy), Surgery(StandardorRobotic),EBRT(includingIMRT), HIFU(HighIntensityFrequencyUltrasound),CRYO (Cryotherapy),Protons,HDR(HighdoseRate Brachytherapy) * Expert panel consensus 2/11/17 12 5. Low-Riskarticlesaminimumof100patients. 6. Intermediate-Riskarticlesaminimumof100patients. 7. High-Riskarticles,becauseoffewerpatients,aminimumof 50patients. 8. Patientsneedtobefollowedforamedianof5years. Foradditionalcriteriainformationcontact:[email protected] 2/11/17 13 RP EBRT/ IMRT Cryo Brachy/ HDR Robot RP 9% 16% 6% 24.8% 5.1% 20% 12.7% 3/50 100/403 5/98 5/20 6/47 37/410 68/427 Proton HIFU Total of 1,502* Treatment Articles. Some articles addressed several treatments and were counted as separate articles for each treatment. *Some articles evaluated other/minor treatments that are not listed here and are therefore not included in these calculations. 2/11/17 14 HowtoInterprettheGraphs ¡ ¡ ¡ ¡ ¡ EachTreatmentisgivenasymbol.ForexampleSeed implantalone(Brachytherapy)isgivenabluedot. EachSymbolisadifferentarticleforthattreatment.At thewebsiteyoucanputacursoroverthesymboland actuallyretrievethatarticle. TreatmentSuccess=PercentofmenwhosePSAnumbers indicateaProstateCancerFree®Status(PSAprogression free)ataspecificpointintime. Thebottomlineindicatesthenumberyearsthestudyis out. Anexample,abluedotpositionedat12yearsalongthe 97%lineindicatesthat,97%ofthepatients,treatedwith seedsaloneinlow-riskpatientsat12yearswerefreeof diseaseprogressionandwereProstateCancerFree®. 2/11/17 15 HowtoInterprettheGraphs ¡ ¡ Thecoloredellipsesoutlinetheresultsofmultiple articlesinthesametreatment.Thesewerecreatedbyour statisticiansusingstandardstatisticalmethods. Theseellipsesdemonstrate2things: § 1.dividingtheellipsesinhalfwillgiveyoutheaverage resultofthetreatment. § 2.Thedirectionoftheellipsewillgiveyouanideaofthelongterm success.Adownwarddirectionoftheellipseindicatesthat somepatientsarefailingovertime. § Ideally,ifatreatmentreachesapointwherenoorfewpatientsfail, theellipsepatternwilllooklikethis. § Thereareinteractiveversionsofthegraphsonthewebsite: 2/11/17 www.pctrf.org/comparing-treatments/Youcanchoosewhich treatmentsandellipsestoviewbycheckingandun-checkingthe boxesinthekeyontheright. 16 ¡ Ellipsesarenotavailableforalltreatments.Theycanonly bedoneifthereare4ormoreacceptedstudieswithinthat treatment,sosometreatmentsmaynotappearonthe slidesasellipsesonlydatapoints. Ingeneral:Brachytherapysymbolsareblue EBRT/IMRTsymbolsaregreen Protonssymbolsareyellow Surgerysymbolsarered Cryotherapysymbolsarepurple HIFUsymbolsaregray ¡ 2/11/17 17 Brachytherapy • Brachytherapyalone • Brachytherapy&EBRT • Brachytherapy,EBRT,&ADT • HDR(Brachytherapy) • HDR&ADT(Brachytherapy) EBRT/IMRT • EBRTalone • EBRT&ADT • HypoEBRT Protons • Protons Surgery • RPSurgery • RoboticSurgery • RPSurgery&EBRT Cryotherapy • Cryotherapy HIFU • HIFU 2/11/17 18 HowtoInterprettheResults ¡ ¡ ¡ TheRiskgroupsaredefinedbyacombinationoffactors. Thesefactorsareprovidedbythediagnosingphysician andincludethestageofthecancer,theGleasonScore, andPSAlevel.Seeslides20,23,and26forspecific definitionsforeachrisk-group. Firstestablishyourclinicalriskgroup*bylookingatthe definitions(youcanalsoaskyourphysicianforhelpin determiningyouriskgroup.)Referonlytothoseslidesfor yourriskgroup. Makeyourownjudgmentandthenaskadoctorineach discipline(Seeds,ExternalRadiation,Surgery,etc.)totell youwherehis/herownpeerreviewedpublishedTreatment *Next Slide Success%wouldfitonthisplot. 2/11/17 19 Thelow-riskgroupisdefinedbyacombinationoffactors. Thesefactorsareprovidedbythediagnosingphysicianand includethestageofthecancer,theGleasonScore,andPSA level.Thelow-riskgroupisdefinedby: § ClinicalStage:T1orT2a,b § GleasonScore<6 § PSA<10ng/ml 2/11/17 20 2/11/17 21 2/11/17 22 Theintermediate-riskgroupisdefinedbyacombinationof factors.Thesefactorsareprovidedbythediagnosingphysician andincludethestageofthecancer,theGleasonScore,andPSA level.Theintermediate-riskgrouphas2definitionsthatcanbe used: ¡ Zelefskydefinition § Only1factor ▪ ClinicalStageT2c ▪ GleasonScore>7 ▪ PSA>10ng/ml ¡ D’Amicodefinition § PSA10-20,GleasonScore7,orClinicalStageT2b 2/11/17 23 2/11/17 24 2/11/17 25 Thehigh-riskgroupisdefinedbyacombinationoffactors.These factorsareprovidedbythediagnosingphysicianandincludethe stageofthecancer,theGleasonScore,andPSAlevel.Thehighriskgrouphas2definitionsthatcanbeused: ¡ Zelefskydefinition § 2ormorefactors ▪ GleasonScore>7 ▪ PSA10-20 ▪ ClinicalStageT1c-T2b ¡ D'Amicodefinition § GleasonScore8-10,PSA>20,ClinicalStage>T2c 2/11/17 26 2/11/17 27 2/11/17 28 Observations ¡ Formostlow-riskpatients,mosttherapieswillbe successful. ¡ Treatmentsatthetopoftheresultscomparisongraphs forthelongperiodsofyears,indicatethatpatients treatedwiththesemethodsdidnotexperiencean increaseinPSAaftertreatment.Thesepatientsaremore likelytoremainProstateCancerFree®.Patientsare encouragedtolookatgraphsanddeterminefor themselves. ¡ Seriousside-effectratesmustbeconsideredforany treatment. 2/11/17 29 LowRisk Stage:T1orT2a,b GleasonScore<6 PSA<10ng/ml IntermediateRisk StageT1orT1-2StageT1-2 GleasonScore7orGleasonScore6 PSA<10PSA10-20 HighRisk StageT2corT3 GleasonScore≥8 PSA>20ng/mL 2/11/17 30 ¡ ¡ ¡ ProstateCancerTreatmentResearchFoundation website:www.pctrf.org ContacttheProstateCancerTreatmentResearch Foundation:[email protected] AdditionalinformationforStudyGroupmembers: www.pctrf.org/study-group-members/ 2/11/17 31