ADJUVANTANDSALVAGERADIOTHERAPYAFTER

PROSTATECTOMY:ASTRO/AUAGUIDELINE
PanelMembers:
IanMurchieThompson*,RichardValicenti*,PeterC.Albertsen,BrianDavis,
S.LarryGoldenberg,CarolA.Hahn,EricA.Klein,JeffMichalski,Mack
RoachIII,OliverSartor,J.StuartWolfJr.andMarthaFaraday.
*Equalauthorcontribution.

Purpose
Thepurposeofthisguidelineistoprovideaclinicalframeworkfortheuseof
radiotherapyafterprostatectomyinpatientswithandwithoutevidenceof
prostatecancerrecurrence.

Methods
AsystematicreviewoftheliteratureusingthePubmed,EmbaseandCochrane
databases(searchdates1/1/90to12/15/12)wasconductedtoidentifypeer
reviewedpublicationsrelevanttotheuseofradiotherapyafterprostatectomy.
Thereviewyieldedanevidencebaseof294articlesaftertheapplicationof
inclusion/exclusioncriteria.Thesepublicationswereusedtocreatethe
guidelinestatements.Ifsufficientevidenceexisted,thenthebodyofevidence
foraparticulartreatmentwasassignedastrengthratingofA(highquality
evidence;highcertainty),B(moderatequalityevidence;moderatecertainty)or
C(lowqualityevidence;lowcertainty)andevidencebasedstatementsof
Standard,RecommendationorOptionweredeveloped.Additionalinformation
isprovidedasClinicalPrinciplesandExpertOpinionwheninsufficient
evidenceexisted.Seetextfordefinitionsanddetailedinformation.

GUIDELINESTATEMENTS
GuidelineStatement1.Patientswhoarebeingconsideredformanagementof
localizedprostatecancerwithradicalprostatectomyshouldbeinformedofthe
potentialforadversepathologicfindingsthatportendahigherriskofcancer
recurrenceandthatthesefindingsmaysuggestapotentialbenefitofadditional
therapyaftersurgery.(ClinicalPrinciple)
GuidelineStatement2.Patientswithadversepathologicfindingsincluding
seminalvesicleinvasion,positivesurgicalmargins,andextraprostatic
extensionshouldbeinformedthatadjuvantradiotherapy,comparedtoradical
prostatectomyonly,reducestheriskofbiochemical(PSA)recurrence,local
recurrence,andclinicalprogressionofcancer.Theyshouldalsobeinformed
thattheimpactofadjuvantradiotherapyonsubsequentmetastasesandoverall
survivalislessclear;oneoftworandomizedcontrolledtrialsthataddressed

theseoutcomesindicatedabenefitbuttheothertrialdidnotdemonstratea
benefit.However,theothertrialwasnotpoweredtotestthebenefitregarding
metastasesandoverallsurvival.(ClinicalPrinciple)
GuidelineStatement3.Physiciansshouldofferadjuvantradiotherapyto
patientswithadversepathologicfindingsatprostatectomyincludingseminal
vesicleinvasion,positivesurgicalmargins,orextraprostaticextensionbecause
ofdemonstratedreductionsinbiochemicalrecurrence,localrecurrence,and
clinicalprogression.(Standard;EvidenceStrength:GradeA)
GuidelineStatement4.Patientsshouldbeinformedthatthedevelopmentofa
PSArecurrenceaftersurgeryisassociatedwithahigherriskofdevelopmentof
metastaticprostatecancerordeathfromthedisease.Congruentwiththis
clinicalprinciple,physiciansshouldregularlymonitorPSAafterradical
prostatectomytoenableearlyadministrationofsalvagetherapiesifappropriate.
(ClinicalPrinciple)
GuidelineStatement5.Cliniciansshoulddefinebiochemicalrecurrenceasa
detectableorrisingPSAvalueaftersurgerythatis0.2ng/mlwithasecond
confirmatorylevel0.2ng/ml.(Recommendation;EvidenceStrength:Grade
C)
GuidelineStatement6.ArestagingevaluationinthepatientwithaPSA
recurrencemaybeconsidered.(Option;EvidenceStrength:GradeC)
GuidelineStatement7.Physiciansshouldoffersalvageradiotherapyto
patientswithPSAorlocalrecurrenceafterradicalprostatectomyinwhom
thereisnoevidenceofdistantmetastaticdisease.(Recommendation;Evidence
Strength:GradeC)
GuidelineStatement8.Patientsshouldbeinformedthattheeffectivenessof
radiotherapyforPSArecurrenceisgreatestwhengivenatlowerlevelsofPSA.
(ClinicalPrinciple)
GuidelineStatement9.Patientsshouldbeinformedofthepossibleshortterm
andlongtermurinary,bowel,andsexualsideeffectsofradiotherapyaswellas
ofthepotentialbenefitsofcontrollingdiseaserecurrence.(ClinicalPrinciple)

Acutetoxicity.PatientsshouldbeinformedthatduringRTandinthe
immediatepostRTperiodoftwotothreemonths,mildtomoderate
genitourinaryandgastrointestinaleffectsthatmayrequiretheuseof
medicationformanagementhavebeenfrequentlyreported,withover90%of
patientsexperiencingtheseeffectsinsomestudies.Serioustoxicityeffectsof

RT,includingthoserequiringaggressivemedicationmanagement,outpatient
procedures,orhospitalization,however,areuncommonorrare,withmost
studiesreportingratesof5%orless.Thelowestacutetoxicityrateshavebeen
reportedwithuseofIMRTRTtechniques.100,175
Latetoxicity.Patientsshouldbeinformedthat,similartoacutetoxicities,mild
tomoderatelatetoxicitiesoccurringmorethan90dayspostRTarecommonly
reportedwithsomestudiesreportingratesashighas79%.Seriouslate
toxicities,however,arerelativelyuncommon,withmoststudiesreportingrates
of10%orless.Patientsalsoshouldbetoldthatinasmallproportionof
patients,latetoxicitiesthataremoderatetomajormayemergeforuptofourto
fiveyearspostRTandmaypersistbeyondthatpoint.Thesetoxicitiesaremore
likelytoincludeGUsymptoms(upto28%ofpatients)129thantoincludeGI
symptoms(upto10.2%ofpatients).99TheuseofnewerRTtechniquessuchas
IMRT,however,isassociatedwithlowercumulativeratesoflateGU(upto
16.8%ofpatients)andGI(4.0%ofpatients)toxicities.99
Urinaryincontinence.Patientsshouldbeinformedthatratesandseverityof
urinaryincontinenceinpatientswhohavehadRPandthenadjuvantRTare
generallysimilartoratesforpatientswhohavehadRPonly.StudiesofSRT
patientsindicatepossiblemildworseningofUIinsmallnumbersofpatients
andisolatedcasesofnewonsetUI.Overall,thePanelinterpretedthesedatato
indicatethatRTisunlikelytohaveamajorimpactonUI.
Sexualfunction.PatientswithintacterectilefunctionpostRPshouldbe
informedthattheimpactofRTonerectilefunctioninmenwhohavealready
hadaprostatectomyisnotclear.Thisuncertaintyderivesfromthefactthatfew
studieshaveaddressedtheimpactofRTonerectilefunctioninpostRP
patientsandalsofromthefactthatmostmenpostRPdonothaveintact
erectilefunction,makingitdifficulttodeterminewhetherRTresultsinfurther
lossoffunction.
AdjuvantRTmayreducetheneedforsalvagetherapies.Patientsalsoshouldbe
informedthattheuseofART,becauseitisassociatedwithimproved
biochemicalrecurrencefreesurvivalcomparedtoRPonly,islikelytoreduce
theneedforsubsequentsalvagetherapies.Salvagetherapiessuchasandrogen
deprivationcanhavedebilitatingsideeffectsandalsopresentincreasedrisks
forosteoporosis,cardiovasculardiseaseandotherhealthproblems.
Secondarymalignancies.Cliniciansshouldadvisepatientsthatthepotential
fordevelopingsecondarymalignanciesexistswhenpostoperativeRTisgiven,
butthatstudiesinvestigatingtheriskofdevelopingsecondarymalignanciesin
menundergoingprostatecancerRTarecontradictory.209210Furthermore,in
clinicaltrialsofadjuvantandsalvageradiotherapynodatahavebeenreported
onsecondarymalignancies.Finally,theriskofsecondarycancersmaybe

relatedtocoexistingbehavioralfactorssuchasthepresenceofpastorcurrent
smoking.212214Therefore,thePanelconcludedthatatthistimetheriskof
developingasecondarymalignancyasaresultofARTorSRTadministration
isnotknown.