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BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department of Urology University of Oklahoma
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Page 1: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

BCG Failure orBCGUnresponsive:DefiningandManagingDifficultPatients

MichaelS.Cookson,MD,ProfessorandChairDepartmentofUrologyUniversityofOklahoma

Page 2: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department
Page 3: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Non-muscleInvasiveBladderCancer

Page 4: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

BladderCancer:Facts

§ 80%presentwith NMIBC:§ 70%Ta(papillary)

§ 20%T1(laminapropria)

§ 10%CIS(highgrade,flat)

Page 5: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

NaturalHistory

• Difficulttopredict(tumorheterogeneity)• Twocharacteristicfeatures:

1. Recurrence:- 70%recurrencewithTURalone

2. Tumorprogression:- 30%tumorprogressionw/TURalone

Page 6: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Treated Natural History of NMIBC 15YearFollow-up

• 86high-riskpatientwithNMIBC• TreatedwithTURaloneorTUR+BCG• Progressionin53%,18%UTT• 36%underwentcystectomy• 15-yrDSSwas63%,34%deadofdisease• Life-longbladderandUTTsurveillance

CooksonMS,HerrHW,etal:J.Urol.1997;158:62–67.

Page 7: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department
Page 8: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

BCGIsStandardofCare

• MostintermediateandallhighriskNMIBC• Superiortointravesical chemotherapy• Supportedbymeta-analysis(9RCTs)

– 68%initialCR– 47%durableCR(3.6yrmedianf/u)

• EndorsedbyAUA,EAUNCCNGuidelines• Bestresultswithmaintenance

SylvesterRJ.JUrol 174:86-92,2005

Page 9: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

HasBecomeU.S.StandardofCareSWOG8507- BCGMaintenance

Lamm,DLetal,JUrol 163:1124,2000

p<0.0001

5-yearRFS60%vs.41%with/withoutmaintenance

2-yearRFS82%vs.62%with/withoutmaintenance

Page 10: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

TheProblem:SomeWillFailBCG

• DespitethebenefitsofBCG,long-termdisease-freeandprogression-freesurvivalmaybedifficulttoachieve

• 50%willrecurafter induction BCG, and ≅30%salvagedwithadditionalBCG

• But,BCGfailuremaybelethalifuntreated• Key:identifyearlythosefailures

LoganCetal.BJUInt.2012;110:12-21

Page 11: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

PotentialCausesofBCGFailure

• Hostimmuneincompetence• Inadequatelyresectedoroccultinvasive• Resistantornon-antigenictumor• Inadequatetreatmentschedule• Inadequatedose:toofewCFU• InadequatecontactofBCGandUCC• ExcessBCGinducingimmunosuppression

Page 12: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

DefinitionsofBCGFailure

§ Intolerant: recurrentdiseaseinsettingofinadequateBCGtreatmentduetosideeffects

§ Resistant: recurrenceoflesserorimprovingdiseasethatresolveswithfurtherBCG

§ Relapsing: recurrenceafterachieving6monthCR,i.e.diseaseresolvesafterBCGthenreturns

§ Refractory:NoCRby6monthsafterBCG...notimprovingorworseningdiseasedespitetwocoursesofBCGormaintenance

Nieder AM, et al. Urology 66:108-125, 2005

Page 13: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Determining BCG Resistance:BCGResponseoverTime

HerrHWandDalbagni G.JUrol 169:1706-08,2003

§ 6monthsisthetreatmentperiodtoidentifyhigh-risktumorsastrulyrefractory

Page 14: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

BCGRefractory

Time0BCG

Induction

Time:3monthsTumor+

Time:6monthsTumor+

Re-inductionorMaintenance

§ Failuretoachieveadiseasefreestate6monthsafterinitialBCGtherapywitheithermaintenanceorretreatmentat3monthsduetoeitherrapidlyrecurrentorpersistenthighgradedisease

HerrHW.JUrol 169:1706-1708,2003Nieder AM,etal.Urology66(S6A):108-125,2005

Page 15: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Ultimately,determiningwhenapatienthas“failed”BCGisashareddecision

betweenurologistandpatient

Page 16: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Novel Definition: MolecularFailure

• Goal:IncorporateFISHtestingtopredictBCGfailurebeforeitbecomesclinicallyapparent

• 143patientstreatedwithBCGIve therapyfollowedprospectivelyfor2years

• FISHassayscollectedat6weeksand3months• ResultsoftheFISHassayswerecorrelatedwithclinicaloutcomes

Kamat AM,etal.BJUInt.2016;117:754-760

Page 17: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

RecurrenceandProgression-FreeSurvivalbasedonFISH

Kamat AM,etal.BJUInt.2016;117:754-760

Page 18: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Novel Definition: MolecularFailure

• Result:FISHresultscorrelatedwithrecurrence

• Conclusion:PatientswithanearlypositiveFISHandanegativecystoscopyat3monthsshouldbeconsidered“molecularBCGfailures”andcouldenrollinprospectiveRCT’s

Kamat AM,etal.BJUInt.2016;117:754-760

Page 19: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

TreatmentDilemma

• CystectomyrecommendedasastandardofcareafterBCGfailure

• Cystectomyhashighrateofcureifbeforeprogressiontomuscleinvasion

• Unfortunately,morbidityremainshigh• And,manywithhighriskNMIBCwhofailBCGarenot

candidatesforcystectomy

Page 20: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

StrategiestoReducePersistenceandRecurrenceofBCGRefractoryCIS

• BetterSurgeryèEnhanceddetectionandmorecompletefulguration

• BetterAgentsè EnhancedIVe chemotherapyandimmunotherapy

• BetterDeliverySystemè EnhancedBladderPenetration

• BetterDiagnosticsè EnhancedPredictiveandPrognosticTools

Page 21: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

PhotodynamicDiagnosticCystoscopy

PDDexploitsthephotoactivepropertiesofcompoundssuchashexaminolevulinate (HAL)(HexvixTM,CysviewTM).Followinginstillation,HALaccumulatesinneoplastictissue.Illuminationwithblue-violetlightproducesaclearlydemarcatedredfluorescencefrommalignanttissue.

BurgerMetal.EurUrol2013

Page 22: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

§ Prospectivestudies:1345patients§ FCcystoscopyusedasanadjuncttowhitelight(WL)cystoscopy§ Outcome:DetectionofNMIBCupto1year§ FCcystoscopydetectedsignificantlymoretumorsthanWL

§ Tatumors(14.7%;p<0.001)§ CISlesions(40.8%;p<0.001)

§ In26.7%,CISwasdetectedonlybyFC(p<0.001)§ RecurrencesweresignificantlylowerwithFC

§ 34.5%vs.45.4%(p=0.006)

Page 23: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

NarrowBandImagingTM (NBI)

Cauberg ECetal.Urol 76:658,2010

• OlympusOpticalimagingtechnologyenhancesvisibilityofvesselsonmucosalsurfaces

• FiltersWLintospecificlightwavelengthsthatpenetrateonlysurfaceofhumantissueandareabsorbedbyHgB

• Bluishlightenhancessuperficialcapillarynetwork(brown)

• Greenishlightenhancesdeepervesselvisibility:vesselsaregreenish-blue(cyan)

Page 24: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

DetectionofCISbyCystoscopyWLandNBI

HerrHW.CurrUrolRep2014

§ Collectively, these studies show superior sensitivity and negative predictive value >90% for NBI over WL

Series No. Cysto Sens. Spec. PPV NPV

Herr&Donat 67 WL/NBI 83/100 72/76 36/36 97/100

Tatsugami 30 WL/NBI 50/90 83/75 76/78 61/87

Cauberg 14 WL/NBI 55/69

Shen 11 WL/NBI 68/77 82/77 75/83

Page 25: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

StrategiestoReducePersistenceandRecurrenceofBCGRefractoryCIS

§ BetterAgentsè EnhancedIVechemotherapyandimmunotherapy

Page 26: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Valrubicin:PivotalStudy

§ Open-label,phaseIIItrial§ 90patientswithCISafterpriorIVe therapy§ 21%CRat6months§ 32%CRat6monthsifyouconsider thatwithlowgraderecurrences(10pts)

§ Overallprogressionwaslow§ But,only8%remainedNEDat30months

SteinbergGetal.JUrol.2000;163:761-7.

Page 27: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Valrubicin:TakeHomeMessage

• FDA-approvedforpatientswithCISwhofailBCGandareunfitorunwillingtoundergoaradicalcystectomy

• DespiteFDAapproval,long-termDFSremainspoorandhighlightstheneedforadditionalbladder-conservingtherapies

Page 28: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Gemcitabine Trials• InhibitsDNAsynthesis• IntroducedbyDalbagni (2002)assafe• EfficacydemonstratedinmultiplePhaseIItrialswithBCGnaïveandsomefailurepatients

BrooksNA&O’DonnellMA:IndianJUrol.2015;31:312-319

Page 29: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Gemcitabine:SWOGS0353• U.S.Phase2Trial• 47patientswithHGTa,T1and/orCISwhohasreceivedat

least2priorcoursesofBCG• Received2gramsin100ccNSqweekx6weeksandtheq

monthx10months• Results:Recurrence-free

– 3months:47%CR– 12months:28%CR– 24months:21%CR

SkinnerECetal,JU2013

Page 30: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Taxane Trials• Inhibitsmicrotubuledepolymerization• IntroducedinBCGfailuresbyMcKiernan(2006)withnodose-

limitingtoxicityat75mg• EfficacydemonstratedinseveralPhaseI/IIstudies,mostwith

someformofmaintenance

BrooksNA&O’DonnellMA:IndianJUrol.2015;31:312-319

Page 31: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Docetaxel

Barlow et al, J Urol 189:834, 2013

§ 54 patients§ All failed prior BCG – 22 had only one prior course§ 83% high grade, 53% with CIS

Recurrence-free SurvivalDFSat12months=40%DFSat36months=25%

Page 32: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Paclitaxel

McKiernan et al, J Urol. 2014; 192:1633-8,

§ PhaseIIstudyof28patientsrecurrentTis,T1andTawhofailedatleast1cycleofBCG

§ 6weeklynab-paclitaxel500mg/100ml,andmonthlymaintenancefor6months

CR35%and8of10completed6months,7of8CRat21months

Page 33: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

BCG+IFNinBCGFailures• Luciani,Urol.2001:

– 9/15(60%)CR(NED)withmedianF/U18months• Lam,Urol Oncol,2003:

– 12/20(60%)NEDwithmedianF/U22months• Punnen,CanJUrol,2003:

– 6/12(50%)NEDat12months• O’Donnell,2004:

– 231pts:42%remainingdisease-freeat24months

Page 34: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

BCG+IFN• Multicenter Phase II: 1,007 pts BCG naïve and failure• At 24 months, 45% of BCG failure were disease-free• Those with >/=2 prior courses of BCG or BCG-refractory had worse

outcomes

Rosevear, J Urol 2011; 186:817

Page 35: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

ForCertainHighRisk,NMIBC: TheMostDefinitiveTherapy

Page 36: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

StrategiestoReducePersistenceandRecurrenceofBCGRefractoryCIS

§ BetterDeliverySystemè EnhancedBladderPenetration

Page 37: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

HyperthermiaSynergy§ Deliveryof

hyperthermicchemotherapywithtemp41°- 44°C

§ Mechanism:-Directcytotoxiceffects-Enhancedpenetrationofchemoagent

CancercellwithMitomycin C deliveredat43°C

Hyperthermia IncreasedIntracellularConcentrationofChemotherapyAgent

Vasodilation

Denatured UnfoldedProtein

Activated Heated ChemotherapyAgent

Increased Permeability of CellMembrane

Heat Shock ProteinsSignaltoNaturalKillerCells

Damaged ImpairedDNA

Page 38: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

MMCandHyperthermia• 160patients:129(80.6%)BCGfailuresfromacombined“10-

yearsinglecenterexperience”• MMCinductionplusmaintenance• MedianF/U75months• RFS:60%(1year)• RFS:47%(2years)• ProgressiontoMIBC:4.3%• 6.3%discontinuedduetoside-effects

ArendsTJH etal.JUrol2014

Page 39: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

HyperthermiaSystems

§ Synergo§ Intravesicalmicrowaveapplicator§ 5thermocouplers deliver

hyperthermiatothebladderviadirectcontact

§ CombatBRS§ BladderRecirculationSystem§ Externalwarmer

vanderHeijdenAGetal.EurUrol2004Souas Aetal.Int JHyperthermia2014

Page 40: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

• Photosensitizingagentwithactivationbylight• Initialreportw/BCGfailureswith5-ALAbyWaidelich (2001)with60%CRinCis

and21%papillarytumors• ALAmaycausehypotensionrequiringintervention• PilotstudieswithHALandRadachlorin showpromise

PhotodynamicTherapy(PDT)

BrooksNA&O’DonnellMA:IndianJUrol.2015;31:312-19

Page 41: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

LotsofMedicationsInTrials

Page 42: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

BCGUnresponsiveClinicalTrialsBCGUnresponsiveTrials

Page 43: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

StrategiestoReducePersistenceandRecurrenceofBCGRefractoryCIS

§ BetterDiagnosticsè EnhancedPredictiveandPrognosticTools

Page 44: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

OptimizingBCGTherapy

• BCGreducesrecurrence andprogression

• ~30%patientsfailBCGtherapy– Innon-responders,diseaseoftenprogressesbeforecurativecystectomy

– Decreasedsurvival

• Ifwecanidentifynonrespondersearly,offeralternatetherapyatearliertimepoint

Page 45: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Jinesh G & Kamat A, Oncoimmunology, 2012

Page 46: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

• Cytokine responsetoBCGdoesdifferentiaterespondersfromnon-responders

• RespondershavehigherlevelsofBCGinducedcytokinesatBCG– 6

• Magnitudeofinductionofcytokinescorrelateswithrecurrencerateandtimetorecurrence

• Complexinterplayofcytokines

CytokinesandBCGResponse

Page 47: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

0%

20%

40%

60%

80%

100%

0 10 20 30 40 50 60

%Rec

urrenc

e-Free

Months

Change 3-2: IL-8 < 1500 Change 3-2: IL-8 ≥ 1500

ΔIL-8with6th BCG

p=0.041

CourtesyofDr.Ashish Kamat,MDACC

Page 48: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

CytokineNomogramPoints 0 10 20 30 40 50 60 70 80 90 100

IL-2 >=200<200

IL-6 >=425<425

IL-8 >=1500<1500

IL-18 >=40<40

IL-1ra -2000 -1500 -1000 -500 0 500 1000 1500 2000 2500 3000TRAIL -400 0 400 800 1200 1600 2000IFN-γ

8000 7000 6000 5000 4000 3000 2000 1000 0 -1000IL-12(p70) -5 0 5 10 15 20 25 30TNF-α 0 100 300 500 700 900Total Points 0 20 40 60 80 100 120 140 160 180 200 220 240Probability of Recurrence

0.01 0.5 0.95

Courtesy of Dr. Ashish Kamat, MDACC

Page 49: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Recommendations• RepeatTURBTwithPPDorNBItechnology• Fulgurateallabnormalappearingareas• If>1yearfromBCG,attemptBCGagain• Ifithasbeen<1yearsinceBCG:ConsiderRC• Ifunwillingorunfitforcystectomy

– Clinicaltrialpreferred– IfHGTa,IVe chemogemcitabine,taxotere– ForCIS,IVe valrubicin

Page 50: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Conclusions:BCGFailure

§ BCGfailuregroupremainspoorlydefined§ Bestsalvagetherapytobedetermined,modestdurableresponseratesmodest

§ Riskofprogressionissignificant,increasingwitheachroundoffailedtherapy

§ Cystectomyremainsthemostdurableoptionforappropriatesurgicalcandidates

Page 51: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Forecast for the Future:We need to develop…

• Markersthatpredictresponseorfailure• BettersurgicalstrategiestoeradicateCIS• Moreeffective,lesstoxicsalvageregimens• Enhanceddeliveryforsalvagetherapy• Personalizedtherapytailoredtoindividualpatientandtumorriskprofiles

Page 52: BCG Failure or BCG Unresponsive: Defining and Managing ......BCG Failure or BCG Unresponsive: Defining and Managing Difficult Patients Michael S. Cookson, MD, Professor and Chair Department

Stephenson Cancer at OU Health Sciences Center


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