Table Of ContentSexual Function in the Prostate Cancer Patient
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Sexual Function in the Prostate
Cancer Patient
Edited by
John P. Mulhall
DepartmentofUrology,CornellUniversityWeillMedicalCollege,
NewYork
Editor
JohnP.Mulhall
CornellUniversity
WeillMedicalCollege
Dept.Urology
525East68thSt.
NewYorkNY10021
USA
[email protected]
ISBN978-1-60327-554-5 e-ISBN978-1-60327-555-2
DOI10.1007/978-1-60327-555-2
LibraryofCongressControlNumber:2008942049
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Foreword
Prostatecancerandsexualfunctionhavebeencloselyintertwinedsincethebegin-
ningofthetwentiethcentury,whenradicalperinealprostatectomywasfirstdevel-
opedbyHughHamptonYoungasaneffectivetherapyforlocalizedprostatecancer.
Itwasimmediatelyrecognizedthattreatmentforprostatecancercameatthecostof
erectilefunction.WiththepioneeringdiscoverybyHugginsandHodgesin1941that
prostatecancerwouldrespondtocastrationortheadministrationofestrogens,loss
ofsexualfunctionbecameindeliblyimpressedinthemindsofbothphysiciansand
thepublicasaninevitableconsequenceoftherapyforprostatecancer.Asradiation
therapybegantogrowasanattractiveformoftreatmentforprostatecancer,therela-
tionshipoftreatmenttosexualdysfunctionbecamemurkier.Manypatientstreated
withradiationwereelderly,theirsexualfunctionbeforetreatmentwaspoorlydocu-
mented,andhormonetherapywasusedindiscriminatelybeforeandafterradiation,
making it difficult to elucidate the effect of radiotherapy on sexual function. The
discoverybyWalshandDonkeroftheanatomicallocationofthecavernousnerves
intheearly1980sandthedevelopmentbyWalshoftheanatomical,“nerve-sparing”
radicalprostatectomybroughtthefieldintomuchsharperfocus.Ratherthansexual
function being an unavoidable consequence of effective prostate cancer treatment,
it became clear that fine details of surgical technique or the precise way in which
the treatment for prostate cancer was delivered had a major impact on the quality
ofsexualfunctionaftertreatment.Walshfirstreported,andthenmanyotherscon-
firmed,thatitwaspossibleformanymentorecoveradequate,evennormal,erectile
functionafterradicalprostatectomyifaskilledprocedurewasdonetoremovethe
entireprostateglandwhilepreservingtheneurovascularbundles.Shortlythereafter,
riskfactorswereidentifiedthatcouldpredicttheprobabilityofrecovery:age,qual-
ity of erectile function before the operation, and quantitative preservation of the
neurovascularbundles.
The modern era of precise measurement of the effects of prostate cancer treat-
mentonsexualfunctionwouldawaitthedevelopmentofmodernoutcomesresearch
methods, especially patient-completed quality-of-life questionnaires. These have
allowed more reliable and precise measurements of the effect of androgen depri-
vationtherapy,radiation,surgery,andothertreatmentsonsexualfunction.
With the availability of noninvasive forms of treatment—intracavernous injec-
tions, vasodilating agents, and oral phosphodiesterase-5 inhibitors—patients with
v
vi Foreword
erectiledysfunctionafterprostatecancertherapyhadmoreoptions.Withtheready
availability of medical information on the Internet and in bookstores, patients’
expectations rose substantially. More and more men became aware of the sexual
side effects of each treatment and much more interested in finding a way to treat
theircancereffectivelywithoutcompromisingsexualfunction.Asaresult,preser-
vationofsexualfunctionhasbecomeanimportantmetricformeasuringthequality
ofprostatecancertherapy.Eventhoughthisoutcomehasbeenreportedfartoocasu-
ally,toooftenassessedonlybythetreatingsurgeons,thepatientsaswellasreferring
physiciansincreasinglydemandtoknowthechancesthatapatientwillrecoversex-
ualfunctionaftertherapy.
Inthiswonderfulandtimelybook,Dr.JohnMulhallhasbroughttogethermany
oftheworld’sexpertsonprostatecancerandsexualfunctiontoassessindetailthe
state-of-the-art.Thesechaptersofferabroadoverviewofthepathophysiologyand
treatment of sexual dysfunction in men with prostate cancer, and leave the reader
withnumerouspearlsofwisdomabouthowsexualdysfunctioncanbeassessedand
preventedinthecareofpatientswithprostatecancer.
Sexual dysfunction presents a major challenge to physicians who take on the
task of treating men with prostate cancer. It is no longer good enough to cure the
diseaseorsavethepatient’slife.Inadiseasethatlingersaslongasprostatecancer,
evenwhenleftuntreatedortreatedpalliatively,patientsdemandthehighestpossible
quality-of-lifecompatiblewiththegreatestlengthoflife.Theyexpectustounder-
standexactlyhowourtreatmentalterstheirfunctionandtodoeverythingwecanto
minimizethedamage.
Wenowknowthatoutcomesofcancertherapy—cancercontrolaswellascom-
plicationsandsideeffects—arerelatedtotheskillandexperienceoftheindividual
surgeon,thedoseandtechniqueofirradiation,andthequalityofcaredeliverysys-
tems.Thebestoutcomerequirestherapydeliveredwiththebestpossibletechnique.
For surgery, this means precise, anatomical dissection that allows preservation of
theneurovascularbundles.Forradiotherapy,thismeansprecisedeliveryofdosage,
eitherthroughbrachytherapyimplantsorintensity-modulatedradiotherapy(IMRT),
to deliver maximum tumoricidal doses to the cancer with minimal collateral dam-
agetothesurroundingtissue.Forsystemictherapy,thismeansrestraintintheuse
ofandrogendeprivationtosituationsinwhichthebenefitclearlyoutweighstheside
effects.
These are challenges that can be met through greater understanding of the
anatomy and physiology of sexual function and through precise measurements of
the effects of each therapy, not only on the cancer but also on sexual function.
Dr.Mulhallandtheauthorsofthisnewtexthaveprovidedavaluablesourceofinfor-
mationthatclearlydefinesthestate-of-the-arttodayandwillundoubtedlystimulate
furtherprogressinthefield.
PeterT.Scardino,MD
Preface
Prostate cancer is the most common form of cancer in American men other than
skincancer.Itisestimatedthatabout185,000newcasesofprostatecancerwillbe
diagnosedin2008intheUSAalone.Almost30,000menwilldieofthediseasein
2008inthiscountry.Itisthesecond-leadingcauseofcancerdeathinmenafterlung
cancer.Whileamanhasa15%chanceofbeingdiagnosedwithprostatecancerin
hislifetime,only3%dieofthedisease.Thus,inthemodernera,thevastmajorityof
menliveforverylongperiodsoftime.Overthecourseofthelast20years,numer-
ousdiscoveriesandrefinementsinmanagementhaveoccurredinthisdisease.There
havebeenrefinementsinprostatebiopsytechnique,inimagingofprostatecancer,
in surgical technique (e.g., the introduction of laparoscopic and robotic prostatec-
tomy),inthedeliveryofradiationtherapy,andinthetreatmentofadvanceddisease.
Furthermore,theuseofPSAasascreeningtoolhasresultedinafargreaternum-
berofmenbeingdiagnosedwithprostatecanceratitsearlieststages.Thishasalso
translated into younger men being diagnosed with prostate cancer. Thus, a man’s
long-termsexualfunctionhasbecomeanevenbiggerissuenowgiventhesefactors.
With regard to the sexual function consequences of the treatment of prostate
cancer, the field has changed dramatically over the course of the last 20 years.
Manyofthedevelopmentsinthisareahavebeen“undertheradar”andhavebeen
missedbymostclinicians.Increasedunderstandingofthepathophysiologyofpost-
prostatectomysexualdysfunctionsandpost-radiationtherapyerectiledysfunction,
the controversial concept of penile rehabilitation, neuromodulatory drugs, and the
impactofandrogendeprivationtherapyonsexualfunctionarebutafewoftheareas
in which information explosion has occurred. The purpose of this book is to give
thepracticingclinician,whetheraurologist,radiationtherapist,medicaloncologist,
internist, or primary care physician, a comprehensive state-of-the-art overview of
sexualfunctionchangesandtheirtreatmentsintheprostatecancerpatient.
I am proud to say that I have been joined in this effort by the world’s leading
authoritiesinthisarea.Iamindebtedtomychairman,Dr.PeterT.Scardino,forhis
masterfulforeword.Dr.Scardinoisasurgeon–scientistwhoneedsnointroduction.
HeisChairmanoftheDepartmentofSurgeryatMemorialSloan-KetteringCancer
Centerandhasmademajorcontributionsinthetreatmentofandresearchinprostate
cancer.
vii
viii Preface
This book opens with a chapter on sexual dysfunctions following prostate can-
cer treatment. It would be remiss of us if we concentrated solely on erectile dys-
functionasthereareothersexualproblemsthatareprevalent,specifically,orgasm
changes, penile length changes, and the development of Peyronie’s disease after
radicalprostatectomy.Clinicalexperience tellsusthataman’serectilefunctionin
themonthsleadinguptohisprostatecancertreatmentisdifferentthanthatbefore
hisdiagnosis.Achapter byDr.David F.Penson andDr.ChristianJ.Nelsonhigh-
lightsthis,dealingwiththeimpactofprostatecancerdiagnosisonsexualfunction.
Dr.KevinT.McVary,aurologist,andDr.CarolA.Podlasek,ascientist,bothworld
authoritiesontheconsequencesofnerveinjuryonerectiletissue,discussthepatho-
physiologyoferectilefunctionchangesfollowingradicalprostatectomyusingtheir
experiencewiththecavernousnerveinjurymodelasanexample.
Dr. Victoria J.Croog and Dr. Michael J. Zelefsky, of the Department of Radia-
tion Oncology at Memorial Sloan-Kettering Cancer Center, follow with a chapter
of the pathophysiology of erectile dysfunction following radiation therapy. Dr. P.
WilliamMcLaughlinandDr.GregoryMerrick,bothradiationoncologists,discuss
theintriguingconceptoferection-sparingradiationtherapyandwhetherthisispos-
sibleornot.Dr.ArthurL.BurnettIIdiscussestheroleofneuromodulatorydrugsin
theradicalprostatectomypatient.Dr.Burnetthascontributedsignificantlytothislit-
eraturefromaclinicalandlaboratorystandpoint.Itisexcitingtothinkthat,atsome
point in time, we may have drugs that prevent cavernous nerve injury or promote
cavernousnerveregenerationatthetimeofsurgeryorevenafterradiationtherapy.
Achapteronintraoperativemaneuversdesignedtominimizepostoperativeerec-
tile dysfunction is written by Dr. Joseph A. Pettus and Dr. Farhang Rabbani. Dr.
Rabbani, one of the world’s authorities on cavernous nerve interposition grafting,
gives a comprehensive and critical account of this strategy. Dr. Alexander Mu¨ller
and I have contributed a chapter on the controversial topic of penile preservation
andrehabilitationandpresenttheanimalandhumandatasupportingthisconceptat
thistime.Dr.RicardoMunarrizandDr.AbdulTraish,aurologistandbasicscientist,
respectively,fromBostonUniversity,highlighttheimpactandrogendeprivationhas
on male sexual function. They present elegant data that outline the severity of the
impactthatanagonadalstatehasonerectilefunction.
Dr.FrancescoMontorsi(thefoundingfatheroftheconceptofpenilerehabilita-
tion)andDr.AndreaSalonia,fromMilan,Italy,discusstheuseofPDE5inhibitors
intheradicalprostatectomypatientpopulationandextensivelyreviewtheliterature
pertainingtotheuseofthesedrugs.Dr.AndrewMcCullough,fromNewYorkUni-
versityMedicalCenter,discussesintracavernosalinjectiontherapy,whileDr.Brian
R. Lane and Dr. Drogo K. Montague, from the Cleveland Clinic Foundation, dis-
cussnon-pharmacologictherapiesforerectiledysfunction,includingpenileimplant
surgery,afterthetreatmentofprostatecancer.
The penultimate chapter is written by Dr. Abraham Morgentaler, from Boston,
whodiscussesthehighlycontroversialsubjectofandrogensupplementationinthe
prostate cancer patient. Dr. Morgentaler, the world’s authority in this area, makes
a cogent argument in favor of a rational approach to the use of androgens in the
prostatecancerpatient.Thebookfinisheswitha“crystalball”viewforthefutureof
Preface ix
post-radical pelvic surgery pharmacotherapy. This chapter is written by Drs. Tony
Bella and Tom F. Lue, from the University of California, San Francisco, and no
oneisinabetterpositiontoaddressthisissuethantheyareDr.Lueistheworld’s
authorityonstemcelltherapyforerectiledysfunction.
Itismyhopethatyou,asaclinician,willfindthisinformationuseful.Further-
more,Ihopethatitwillattheveryleastprovokeyouintothinkingdifferentlyabout
theseproblemsinthispopulationandperhapsevenalterhowyoupractice.
JohnP.Mulhall,MD
Contents
Foreward ........................................................ v
Preface........................................................... vii
Contributors ..................................................... xiii
ColorPlates ...................................................... xix
Chapter1 SexualDysfunctionAfterRadicalProstatectomy .......... 1
RaananTalandJohnP.Mulhall
Chapter2 TheImpactofProstateCancerDiagnosisand
Post-treatmentSexualDysfunctiononQualityofLife ...... 17
DavidF.PensonandChristianJ.Nelson
Chapter3 PathophysiologyofErectileDysfunctionFollowingRadical
Prostatectomy ......................................... 33
JoshuaModder,CarolA.Podlasek,andKevinT.McVary
Chapter4 Pathophysiology of Erectile Dysfunction Following
RadiationTherapy ..................................... 55
VictoriaJ.CroogandMichaelJ.Zelefsky
Chapter5 Evolution of Radical Prostatectomy as It Pertains to
Nerve-Sparing ......................................... 69
OferYossepowitchandJamesA.Eastham
Chapter6 Laparoscopic and Robotic-Assisted Radical
Prostatectomy:SexualFunctionOutcome................. 83
PhillipePaparel,JavierRomeroOtero,BertrandGuillonneau,
andKarimTouijer
xi
xii Contents
Chapter7 Potency-SparingRadiation:MythorReality? ............. 91
P.WilliamMcLaughlinandGregoryMerrick
Chapter8 NeuromodulatoryDrugsfortheRadicalProstatectomy
Patient................................................111
ArthurL.BurnettII
Chapter9 NerveGraftingatRadicalRetropubicProstatectomy:
Rationale,Technique,andResults........................129
JosephA.PettusandFarhangRabbani
Chapter10 Erectile Function Preservation
andRehabilitation .....................................139
AlexanderMu¨llerandJohnP.Mulhall
Chapter11 ImpactofAndrogenDeprivationonMaleSexual
Function ..............................................163
RicardoMunarrizandAbdulTraish
Chapter12 TheUtilityofPDE5InhibitorsAfterRadical
Prostatectomy .........................................177
AndreaSalonia,AlbertoBriganti,AndreaGallina,
andFrancescoMontorsi
Chapter13 InjectableTherapiesAfterProstateCancerTherapy.......197
AndrewMcCullough
Chapter14 Non-pharmacologicErectileDysfunctionTreatmentsAfter
ProstateCancerTherapy ...............................209
BrianR.LaneandDrogoK.Montague
Chapter15 AndrogenSupplementationintheProstateCancer
Patient................................................233
AbrahamMorgentaler
Chapter16 Future Therapies Applicable to Post-radical Pelvic
SurgeryPatients .......................................245
AnthonyJ.Bella,WilliamO.Brant,andTomF.Lue
Index .............................................................257
