prostate health review

7/29/2019 Prostate Health Review

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AssessingProstateHealth

1

Christopher French MD FRCSCClinical Assistant Professor of SurgeryMemorial University of Newfoundland

Tuesday, 2 October, 12



Disclosures–Dr.ChristopherFrenchMD,FRCSCUrology,EasternHealth

Speakerhonorariuminpast12monthsfrom:- GlaxoSmithKline

- AstraZeneca




ProgramObjecvesUponcomple*onoftheprogram,par*cipantswillbe

ableto:

1. Defineanddifferen*atebenignprosta*chyperplasia

(BPH)andlowerurinarytractsymptoms(LUTS)2. Recognizeclinicalimplica*onsofdiseaseprogression

3. Dis*nguishandpreciselydefinetherolesofconserva*vemanagement,alpha-blockers,5-alphareductaseinhibitorsandcombina*ontherapyinthemanagementofBPHandLUTS

4. CitetheCanadianguidelinesonthediagnosisandmanagementofLUTSandBPH

5. Applytheevidenceforalpha-blockers,5-alphareductaseinhibitorsandcombina*ontherapytotheclinicalmanagementofpa*entswithLUTSandBPH




CasePresentaon:Jeff • Jeffisa55-year-oldmaningoodhealth.

• Duringhisannualexam,hecomplainsoftroublesurinaFng.Heisconcernedabouthisriskofprostate

cancer.




DiscussionPoints• Whatconcernsdrivementoseeadoctorabouttheirurinarysymptoms?

• Whatarethebarrierstomenseekingtreatment?

• WhatareyouriniFalinvesFgaFonsforJeff?




EvaluaonofLUTS/BPHHistory(Mandatory)

• Symptomandbother

assessment

– Priorandcurrentillnesses – CurrentmedicaFons

NickelJC,etal.Availableonlineat:hp://www.cua.org/guidelines/bph_2009_en__v2a.pdf.LastaccessedonJuly30,2010.




EvaluaonofLUTS/BPH• PerformaDRE

• Inspecttheurethratoruleoutobviousstenosis

• eeltheabdomentoruleoutadistendedbladder

• Afocusedneurologicexammaybeconsidered




EvaluaonofLUTS/BPH

Descriptors WhatToFeelFor

Small 10−30cc Normal Nomorethan1fingerwidtheither

sideofmidline

Medium 30−50cc 1+ 1−2fingerwidthseithersideofmidline

Large 50−70cc 2+ 2fingerwidthseithersideofmidline

VeryLarge

70−90cc 3+ 2−3fingerwidthseithersideofmidline

>90cc 4+ 3+fingerwidthseithersideofmidline

PinskyP,etal.Urology 2006;68:352-6.




DREReporngDescriptors:Consistency

Parameter Descriptors WhatToFeelFor

Consistency Boggy

So

Normal

Benign

“Boggy”typicallydescribesaninflamedprostate(prosta**s);feelslikepressingagainstyourcheek.

“SoV”istypicallyequatedwith“normal”.Likepressingagainstthenareminence.

Firm

“Firm”isaverysubtledescrip*on.Mayequatewithnormal;however,focalareasthatarefirmerthanelsewhereareconcerning.Likepressingagainstapinkeraser.

Indurated(hard)

NodularWorrisomeforMali nanc

Anyhardnessornodularityisconcerningformalignancy.(NB.“SoVnodules”aresome*mesfelt,butshouldalwaysbefurtherevaluated.)

Symmetry Prostatemayg furtherevalua

rowasymmetricall ed.

;however,anyfocalasymmetryshouldbe




ClinicalDREPearlsforthePrimaryCarePhysician:ThingstoFeelfor

1. Nodularity

2. Asymmetry/irregularity3. Abnormalfirmness




EvaluaonofLUTS/BPHSymptomInventory(OpXonal)

InternaFonalProstateSymptomScore(IPSS)

• Validated,widelyusedinmostBPHstudies

• Usefultooltoassessbaselinesymptomsandmonitorprogressionandtreatment

• Symptomassessment(7quesFons,Score0−35) – 0−7:mild

– 8−19:moderate – 20−35:severe

• Botherindex(onequesFon,Score0−6)

KirbyRandLeporH.In:Campbell’sUrology,9thediFon.Philadelphia,Pa:Saunders;2007:2766-2802.MadersbacherS,etal.EurUrol2004;46:547-54.




EvaluaonofLUTS/BPH• RequiredtoruleoutdiagnosesotherthanBPH

–Posi*vepredic*veforcancerorotherurologicdiagnosisis4−26%

•PresenceofbacteriaorpuscellsmayrequirefurtherinvesFgaFonorurologicassessment

• Presenceofbloodmayrequirecytology,cystoscopyanduppertractimaging

NickelJC,etal.Availableonlineat:hp://www.cua.org/guidelines/bph_2009_en__v2a.pdf.

LastaccessedonJuly30,2010.;Kirby,LeporH.2007;2766-2802.




EvaluaonofLUTS/BPHProstate-SpecificAngen(Recommended)

• Toruleoutprostatecancer

(>10yearlifeexpectancy) –ElevatedPSAforage

–Asasurrogateforprostatesize

NickelJC,etal.Availableonlineat:hp://www.cua.org/guidelines/bph_2009_en__v2a.pdf.LastaccessedonJuly30,2010.;www.prostatecentre.ca/diagnosis_psa.html;RhodenEL,MorgentalerA.NewEnglJMed2004;5:482-492.


http://www.prostatecentre.ca/diagnosis_psa.html








AgeandSerumPSAcanHelpIdenfy

*EachpredicFonissubjecttoanerrorofapproximately±5mL.

TheseresultsarebasedonthetrialpopulaFonstudied,andesFmatetheaverageprostatevolumefora

givenageandPSAlevel.

AdaptedfromRoehrbornC.Urology1999;53:581.

PSA 1.5 ng/mL

1 2 3 4 5 6 7 8

SerumPSA(ng/ml)

30

35

40

45

50

5560

65

70

P r o s t a t e v o l u m e ( c c )

75

70

65

6055

504540

Predictedprostatevolumevs.serumPSAlevelatvariousages




PSAScreening• BPH/LUTSpresentaFoniscasedetecFonandnotscreening.

• RealworldpaFentsmayaskaboutscreeningbeforesymptomsorwithmildLUTS

• DiscussionofrisksandbenefitsofPSAtest

• Prostatecancerriskfactors – Age,amilyHxandEthnicity

15




PLCO Dataset

76693 men screened

Yearly DRE and PSA

Vs “Usual Care”

116 per 10000 screened

95 per 10000 usualcare

Conclusion: At 7-10 years follow-up

The death rate of prostate cancer was low

And did not differ significantly.

But Controls are suboptimal in this study and low compliance in f/u.




182000 men randomized to

Screening every 4 years

Compared to control.

Age 55=69

Mean follow up 9 yrs

Incidencescreened 8.2%

control 4.8%

Conclusion: PSA based screening reduced the

death rate of prostate cancer by 20% but

resulted in a high risk of overdiagnosis




18

Source:CFP JournalSept 2012




DiscussionPoint• Jeff’sprostatevolumeisenlarged(~30-40cc)andheisfoundtohaveaPSAof1.5ng/mL.Youreassurehimthathedoesnothave

prostatecancer.• WhatdoyouadviseJeffabouthisriskof progression?




LUTSandBPHareCommoninMen• LUTSandBPHarecommonandincreasewithage

• Importanttake-homepoint: –BPHisprogressiveinmanymen,leadingtoworseningsymptoms,complicaFons,needforsurgicalintervenFon,andimpacFngqualityoflife

IrwinD.EurUrol2006;50:1306.;ArrighiH.Urology1991;38(Suppl):4.RosenR.EurUrol2003;44:637.




MarkersofIncreasedRiskofBPHProgression

• Enlargedprostatesize(>30cc)

• PSA(asasurrogateforprostatesize)

≥1.5ng/mL• Age>50years

AndersonJ.EurUrol2001;39:390.;MadersbacherS.EurUrol2007;51:1522.;MarksL. JUrol2006;176(4Pt1):1299.;DjavanB.CurrOpinUrol2004;14:45.;

RoehrbornC.BJUInt2006;97(Suppl2):7.




DiscussionPoint• Jeffwantshissymptomsmanaged

• HowwouldyoucounselJeff,basedonhisriskofprogression,abouthowtomanage

hissymptomsandop>mizeoverall prostatehealth?




PaentswithLUTSSecondarytoBPH

Treatbothersomesymptoms

Improvehealth-relatedqualityoflife

IdenFfyandcounselmenontheriskofprogressionandthegoaltoprevent

complicaFons

IdenFfyearlymenwhoshouldbereferredtoaurologist




CanadianGuidelinesfortheManagement

TYPICAL MAN PRESENTING WITH LUTS

Mild Symptoms Moderate - Severe Symptoms

Large Prostate

WatchfulWaiting Watchful

Waitingor

5-alphaReductase

Therapy

No Significant Bother Moderate - Severe Bother

Small Prostate Large Prostate Small Prostate Large Prostate

WatchfulWaiting

WatchfulWaiting

or 5-alpha

ReductaseTherapy

Alpha-blocker Therapy

or SurgicalOptions

Alpha-blocker Therapyor

5 Alpha ReductaseTherapy

or Combination Therapy

or Surgical Options

Small Prostate





CanadianGuidelinesfortheManagement

TYPICAL MAN PRESENTING WITH LUTS

Mild Symptoms Moderate - Severe Symptoms

Large Prostate

WatchfulWaiting Watchful

Waitingor

5-alphaReductase

Therapy

No Significant Bother Moderate - Severe Bother

Small Prostate Large Prostate Small Prostate Large Prostate

WatchfulWaiting

WatchfulWaiting

or 5-alpha

ReductaseTherapy

Alpha-blocker Therapy

or SurgicalOptions

Alpha-blocker Therapyor

5 Alpha ReductaseTherapy

or Combination Therapy

or Surgical Options

Small Prostate


SYMPTOMS

BOTHER

SIZETuesday, 2 October, 12



ConservaveMeasuresto

• WatchfulwaiFng – Educateandreassure – Reduceeveningfluids

– Avoiddecongestants/anFhistaminesandotherdrugsthatexacerbatesymptoms

– Avoidbladderirritants(eg,caffeine)

– Avoid/treatconsFpaFon

– SmokingcessaFon





DiscussionPoint• Asareminder,Jeffhas:

–Moderatesymptoms

–Moderatebother

–Enlargedprostate –PSA=1.5ng/mL

• HowwouldyouapproachJeff’sLUTS?




Alpha-blockers

• RapidlyimprovesymptomsandurinaryflowbutdonotreduceprostatesizeoraffectPSA

• AcceptableopFonforpaFentswithmoderate/

severeLUTSandsmallprostates – ailureratemaybeincreasedinmenwithmedium-

largeprostates(overall5-yrfailurerate15-40%)

• Donotreducetheoveralllong-termriskof

urinaryretenFonorneedforsurgery

DjavanB.EurUrol1999;35:1.;McConnellJ.NEnglJMed2003;349:2387.;




CommonAlpha-blockersAGENTS DOSE

NonselecXve

Terazosin(Hytrin™) 2−10mgdaily

Doxazosin(Cardura™) 1−8mgdaily

SelecXve

Tamsulosin(Flomax™,FlomaxCR™) 0.4mgdaily

Alfuzosin(Xatral™) 10mgdaily

MilaniS,DjavanB.BJUInt2005;95(suppl4):29-36.

Kirby,LeporH.2007;2766-2802.




Alpha-blockerSideEffects

• Posturalhypotension 5% – Dizziness 5−15%

• Nasalconges*on 5%

• Headache 5−10%

• Asthenia 5−10%

• Abnormalejacula*on – Tamsulosin 3−10%

• Erec*ledysfunc*on(maycauseorimproveED!)

KirbyRandLeporH.In:Campbell’sUrology,9thedi*on.Philadelphia,Pa:Saunders;2007:2766-2802.MilaniS.BJUInt2005:95(suppl4);29

PatelA.BMJ2006;333:535.




Jeff:One-yearFollow-up• Jeffwasstartedonanalpha-blocker.

• ResultswereiniFallygood,butaer1year,hissymptomshaveworsened. –Symptoms:moderate

–Bother:moderate

• DRE – Prostate“enlarged”(appreciablywiderthan1fingerper

sideofmidline)

• Lab

– Urinalysisnormal – PSA1.6ng/mL




DiscussionPoints

• DiscussthepotenFaloutcomeforJeffifhehadbeeniniFallytreatedwitha5ARIincombinaFonwithanalpha-blocker.

Whatdoestheevidencesay?• WhatarethenextstepsinJeff’smanagement?




Dutasteride

Dutasteride

Finasteride

Prostate

SizeReduced

DHTTestosterone

5-alphaReductaseInhibitors(5ARIs)

BartschG.EurUrol2000;37:367.SteersW.Urology 2001;58(suppl6A):17.

x x

x

5-AR = 5-alpha reductase; DHT = dihydrotestosterone

Type I 5AR

Type II 5AR




5ARIEfficacy:Summary

• Dutasterideandfinasteridehaveasignificanteffecton: –Reducingsymptoms(30%frombaseline)andimpactofBPH

–Reducingprostatesize(20-30%) –Improvingurinarystream(1−2ml/sec) –ReducingriskofurinaryretenFonandsurgery(>50%)

• Improvementsaregenerallyseenaer

approximately6monthsormoreandconFnuetobuildbeyond2yearsoftherapy

McConnellJ.NEnglJMed1998;338:557.RoehrbornC.Urology 2002;60:434.




Alpha-blockervs5ARIforProgressiveBPH

RoehrbornC.Urology 1999.;54:662.;McConnellJ.NEnglJMed2003;349:2387.;RoehrbornC. JUrol2008.;179:616.;RoehrbornC.EurUrol2010;57:123.

Alpha-blockers 5ARIs

Symptomrelief Superiorinshort-termFailureratesdependonprostate

size,symptomseverity,

dura*onoftherapy

Equivalent/beerinlong-termandwithlarger

prostates

AffectonPSA None Lowerby~50%in~6months

Preven*onofdiseaseprogression

No Yes

AErates 5−15% 5−10%

Combination therapy offers the potential for optimumearly symptom control and long-term success




EvidenceSupporngCombinaon

Therapy• inasteride:MTOPS(MedicalTherapyofProstateSymptoms)

•MeningeneralpopulaFon>50y/oRxwithplacebo,finasteride,doxazosin,orcombinaFon.3,047men,followedfor4.5years

• CombinaFontherapywassuperiorinreducingsymptomsandimprovingstream,andinreducingriskofAURorsurgery

• Dutasteride:CombAT(CombinaFonofAvodart®andTamsulosin)Study

•Menatriskofprogression,randomizedtotamsulosin,dutasteride,orcombinaFon,followedfor4years.

• irstFmeinaclinicaltrialamonotherapy5ARIshowsimprovementoveramonotherapyalphablockeratthe15-monthFmepoint.

McConnellJ.NEnglJMed2003;349:2387.RoehrbornC. JUrol2008;179:616.




0 12 24 36 48

CombinationDutasteride

Tamsulosin

Time (months)

P e r c e n t o f p a

t i e n t s

67%

58%

p<0.001

14

13

12

11

10

9

87

6

5

4

3

2

1

0

NNT=13

RoehrbornC.EurUrol2010;57:123.

CombAT:PrimaryOutcome–TimetoAUR




SymptomImprovement

LOC=lastobservaFoncarriedforward*PaFentsgenerallyperceivea3-pointchangeintheAUA-SIscoreasmeaningful

-8.0

-6.0

-4.0

-2.0

0

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48

C h a n g e ( u n i t s

)

Treatmentmonth

IPSS—AdjustedMeanChangeFromBaseline(LOCF)

*

Tamsulosin(n=1582)

Dutasteride(n=1592)

CombinaXon(n=1575)

-4.3

-4.9

-6.2

-3.8

-5.3

-6.3

P <0.001CombinaXonvsDutasteride

P <0.001CombinaXonvsTamsulosin

RoehrbornC.EurUrol2010;57:123.




Whattodowiththealpha-blocker?

• InmentreatedwithcombinaFontherapy,removalofthealpha-blockeraer6-9monthsoftherapyisreasonable

• ThemajorityofmenwillconFnuetoenjoygoodsymptomcontrol

• Thosewithmoreseverebaselinesymptomsmayrequirethatthealpha-blockerbe

conFnuedlonger-term

NickelJC,Méndez-ProbstCE,etal.2010;BarkinJ.EurUrol2003;44:461.;BaldwinK.Urology 2001.;58:230.;NickelC.CUAJ2008;2:16.




5ARISideEffects

• Decreasedlibido 3−8%

• Ejaculatorydisorder 1−5%

• ErecFledysfuncFon 5−10%

• Breasttenderness 1%

• GynecomasFa 1%

Side effects are mild and decrease with duration of therapy

RoehrbornCG,etal.Urology 2004;63:709-715.;LoweFC,etal.Urology 2003;61:791-6.;MarksLS.CurrUrolRep2006;7:293-303.




PSATesnginPaentson5ARI

• BaselinePSAiscriFcal

• RepeatPSAaer6monthstreatment(newbaseline)

• PSAwillremainsuppressedon5ARItherapy – ProgressivelyrisingPSAontreatmentisan

indicaFonforreferral

RoehrbornCG,etal.Urology 1999;53:581-589.McConnellJD,etal.AHCPR,No.94-0582,1994.




Prostate-SpecificAngen

Treatment month

M e d i a n c h a n g e ( % )

RoehrbornC.EurUrol2010;57:123

0

-53.7 -55.0 -56.0

0

0.0

12.518.4

-55.6 -55.7 -57.1-70

-60

-50

-40

-30

-20

-10

0

10

20

30

12 24 48

Dustasteride Tamsulosin CombinaXon

0




SuggestedClinicalApproachEnlargedProstate,ModerateSymptoms


LastaccessedonJuly30,2010.





• Startalpha-blockerforimmediaterelief – ollow-upin1−3months

• Importanttomonitorfor

– ConservaFvemeasures – Compliance – Sideeffectsandefficacy(symptoms,bother)

• Consideradding5ARIorstartwithcombinaFontherapyforlong-termbenefit

– MeasurebaselinePSA – ollow-upin6−9months

• Monitorasabove,repeatPSA







• Startalpha-blockerforimmediaterelief – ollow-upin1−3months

• Importanttomonitorfor

– ConservaFvemeasures – Compliance – Sideeffectsandefficacy(symptoms,bother)

• Consideradding5ARIorstartwithcombinaFontherapyforlong-termbenefit

– MeasurebaselinePSA – ollow-upin6−9months

• Monitorasabove,repeatPSANB. It is also acceptable to (a) start 5ARI monotherapy if patient is okay waiting longer for symptom improvement, or (b) start both drugs together






IndicaonsforReferral




IndicaonsforReferral

• AbsoluteindicaFonsforsurgery – Acuteorchronicurinaryreten*on – Hematuria,infec*ons,orrenalinsufficiencyfelttobe

secondarytoBPH

• ailureofmedicaltherapyorinabilitytotolerate – Drivenbypa*entpercep*on,sa*sfac*on,riskofprogression

– Alpha-blockersshouldshowefficacywithin1month – 5ARIsshouldshowefficacywithin~6months

• Cancerconcern

– ElevatedbaselinePSAorabnormalDRE – ConsistentlyrisingPSA

*AcuteurinaryretenFon:reasonabletofirststartalpha-blocker,thentrialofvoidingwithoutcatheter48hourslater.**MayvarywithdoseFtraFon.




DiscussionPoint

• Jeffreturnsaeroneyearandhissymptomshaveimproved

• Lab –Normalurinalysis

–PSA0.75ng/mL

• Heraisesconcernsaboutprostatecanceragain.

• Whatdoestheevidenceshowinregardtothe preven>onofbiopsydetectableprostatecancer

with5ARIs?




ProstateCancer

ChemoprevenonStudies

• TheProstateCancerPrevenFonTrial(PCPT) – ThompsonI.Urology 2001;57(Suppl4A):230.

• REducFonbyDUtasterideofprostateCancerEvents(REDUCE) – AndrioleG.NEnglJMed2010;362:1192-202.

5ARIsarenotcurrentlyindicatedforprostatecancerriskreducFon




5ARITrialsforCancerPrevenon

PCPT REDUCE

StudyduraXon 7years 4years

No.ofsubjects 18,882 ~8000

LocaXon U.S.only InternaXonalBaselinebiopsies No Yes(1negbx)

Follow-upbiopsies 7years 2and4years

PSAentrycriteria <3.0 2.5−10.0

FreePSA --- <25%

Age ≥55 ≥50

RoehrbornCG,etal.EurUrol2010;5:123-31.AndrioleG.NEngJMed2010;362:1192.




PCPT:Seven-yearPrevalence

24.4%

18.4%

0%

5%

10%

15%

20%

25%

30%

Finasteride Placebo

P r o p o r X o n o f M e n

w i t h

P r o

s t a t e C a n c e r D e t e c

t e d ( % )

RRR24.8%

P<0.001

ThompsonI.NEnglJMed2003;349:215.




REDUCE:ProporonsofMenwitha

9.1%

11.9%13.4%

17.2%

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

Yr1-2 Yr3-4

Dutasteride

Placebo

P r o p o r X o n o f M e n

w i t h

P r o

s t a t e C a n c e r D e t e c

t e d ( % )

AndrioleG.NEnglJMed2010;362:1192.

RRR22.4%

P<0.001

RRR23.7%

P<0.001

RRR31.4%(95%CI12.3-46.2)withdutasterideinmenwithaposiFvefamilyhistoryofprostatecancer




5ARIsforProstateCancer

RiskReducon• Enlargedprostate(>30cc)• PaFentconcernsofprostatecancer• Highriskforprostatecancer

• ElevatedPSA• amilyhistoryofprostatecancer

Importanttake-homepoint:• 5ARIsprovidetheaddiXonalbenefitof

prostatecancerriskreducXoninmenwithLUTSwhoareatrisk

ThompsonI.Urology 2001;57(Suppl4A):230.AndrioleG.NEngJMed2010;362:1192.




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