Initial Management of High-Risk Gestational Trophoblastic Neoplasia

2/4/2015
Initialmanagementofhighriskgestationaltrophoblasticneoplasia
Officialreprintfrom UpToDate
www.uptodate.com 2015UpToDate
Authors
RossSBerkowitz,MD
DonaldPeterGoldstein,
MD
NeilSHorowitz,MD
SectionEditor
BarbaraGoff,MD
DeputyEditors
DonSDizon,MD,FACP
SandyJFalk,MD,FACOG
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jan2015.|Thistopiclastupdated:Jan06,2015.
INTRODUCTIONGestationaltrophoblasticdisease(GTD)definesagroupofconditionsthatarisefroman
aberrantfertilizationevent.WhenGTDrecursorthereisevidenceofmetastaticdisease,itiscalledgestational
trophoblasticneoplasia(GTN)andcomprisesfoursubtypesofdisease:
Invasivemole
Choriocarcinoma
Placentalsitetrophoblastictumor(PSTT)
Epithelioidtrophoblastictumor(ETT)
TheinitialtreatmentofhighriskGTNisdiscussedhere.Thepathology,epidemiology,clinicalmanifestations,
andstagingofGTDarediscussedseparately.Inaddition,themanagementoflowriskandrecurrentGTNare
alsodiscussedseparately.
(See"Hydatidiformmole:Epidemiology,clinicalfeatures,anddiagnosis".)
(See"Gestationaltrophoblasticdisease:Pathology".)
(See"Hydatidiformmole:Management".)
(See"Initialmanagementoflowriskgestationaltrophoblasticneoplasia".)
DEFINITIONOFHIGHRISKDISEASEHighriskgestationaltrophoblasticneoplasia(GTN)ischaracterized
bytheInternationalFederationofGynecologyandObstetrics(FIGO)stageandtheWorldHealthOrganization
(WHO)riskscore(table1)(see"Gestationaltrophoblasticneoplasia:Epidemiology,clinicalfeatures,diagnosis,
staging,andriskstratification",sectionon'Stagingandriskassessment'):
StageIVdisease
StagesIIandIIIwithriskscore>6
Ofnote,theWHOPrognosticScoringSystemisnotapplicabletopatientswithplacentalsitetrophoblastic
tumor(PSTT)orepithelioidtrophoblastictumor(ETT),andthosepatientsarenotcategorizedaseitherlowrisk
orhighrisk.Theyare,however,stagedbasedontheFIGOStage.Themanagementofthesepatientsis
discussedbelow.(See'Placentalsiteorepithelioidtrophoblastictumor'below.)
APPROACHTOTREATMENTGestationaltrophoblasticneoplasia(GTN)isuniquelysensitiveto
chemotherapy,whichisthemajortreatmentmodalityforpatientswithhighriskdisease.Theexceptiontothis
iswomenwithplacentalsitetrophoblastictumor(PSTT)orepithelioidtrophoblastictumor(ETT),inwhichcase,
theprimarytreatmentmaybeacombinationofsurgeryandchemotherapy,primarilybecausePSTTandETT
arerelativelyresistanttochemotherapyascomparedwithchoriocarcinomaandinvasivemole.Regardless,in
thetreatmentofhighriskGTN,othermodalitiessuchassurgeryandradiationtherapy(RT)maybeindicatedin
additiontochemotherapy.
Forpatientsinwhomcombinationchemotherapyisindicated,treatmentmayresultinovarianinsufficiency.
Therefore,weadvocatefortheuseoforalcontraceptivestosuppressthepituitaryglands'productionof
luteinizinghormonewhichaimstoprotecttheovariesfromthetoxicityofchemotherapyandalsosuppressthe
productionofhumanchorionicgonadotropin(hCG),whichinourclinicalexperience,couldfalselysuggestthe
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presenceofactivediseaseifnotsuppressed[1].(See"Fertilitypreservationinpatientsundergoinggonadotoxic
treatmentorgonadalresection",sectionon'Gonadalsuppression'and"Hydatidiformmole:Management",
sectionon'Contraception'.)
ChemotherapyPatientswithhighriskGTNarelikelytodevelopdrugresistanceifsingleagenttherapyis
administered.Therefore,thesepatientsarecommonlytreatedwithmultiagentregimens.Evidenceofthe
greaterlikelihoodofresistancetosingleagentchemotherapycomesfromaretrospectivestudythatincluded
over300patientstreatedfornonmetastaticGTN[2].Althoughallpatientswerecured,27of253patients(11
percent)initiallytreatedwithmethotrexate(MTX)developedresistance.Inthisseries,onlysixpatients
experiencedarelapseafterobtainingaremissionofthese,fivepatientshadachoriocarcinoma.
Ourpreferredregimenforthesepatientsisetoposide,MTX,plusactinomycinD(ActD)alternatingwith
cyclophosphamideandvincristine(EMACO)becauseitresultsincompleteresponseratesbetween71and78
percentandlongtermsurvivalratesof85to94percent[311].However,a2012Cochranereviewhasfoundthat
regimensthatincorporateetoposideandcisplatinareeffectiveoptions,thoughthelackofrandomizedtrials
preventedananalysistodefinetheoptimalregimen[12].
EMACOEMACOhasemergedastheregimenofchoiceforinitialtreatmentofhighriskGTN.Thisis
predominantlybasedonretrospectivedatathatconsistentlyshowitisactiveinhighriskGTNandisassociated
withalowtoxicityprofile[12,13].
Thecomponentsofthisregimenare[11]:
Etoposide100mg/m2IVover30minutesondays1and2
MTX100mg/m2IVbolusfollowedby200mg/m2IVover12hoursonday1
ActD0.5mgIVbolusondays1and2
Leucovorincalcium15mgorallyevery12hoursforfourdoses,starting24hoursafterstartofMTX
Cyclophosphamide600mg/m2IVonday8
Vincristine1.0mg/m2IVonday8
AlthoughEMACOisthemostwidelyusedregimen,therehavebeennorandomizedtrialstodemonstratethatit
shouldbethepreferredregimen.However,comparedwithothercombinationregimens,itappearstobeas
effective(ifnotmoreso)andbettertolerated.
Thiswasshowninonereportthatincludedover200womenwithhighriskGTNtreatedwith[13]:
MTXplusActDandfolinicacid(MA,administeredbetween1971and1995)
MTX,ActD,cyclophosphamide,doxorubicin,melphalan,hydroxyurea,andvincristine(CHAMOCA,
administeredbetween1982and1995)
MTX,ActD,andchlorambucil(MAC,administeredbetween1971and1982)
EMACO(administeredbetween1985and1995)
Ofthesefourregimens,EMACOresultedin[13]:
Thehighestremissionrate(91percent)comparedwithMA,CHAMOCA,andMAC(63,76,and68
percent,respectively)andrequiredthefewestnumberofcoursestoattainremission
Thelowestmortalityrate(9percentversus37,22,and33percent,respectively)
Ina2012systematicreview,theadministrationofEMACOwasassociatedwithprimaryremissionrates
rangingfrom54to91percentofpatients[12].ThesedatasupporttheuseofEMACOasaprimarytreatment
forhighriskGTN.
AdministrationTreatmentwithEMACOshouldbeadministeredeverytwotothreeweeks.Althougha
treatmentdelayordosereductionmayberequiredduetosideeffects,theseshouldbeavoidedasbothhave
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beenassociatedwithlessthanoptimaloutcomes.
TreatmentshouldbecontinueduntilthehCGlevelbecomesundetectableandremainsundetectableforthree
consecutiveweeks.Finally,weadministeratleastthreecoursesofEMACOafterthepatientachieves
undetectablehCGlevelsasconsolidationtherapytoreducetheriskofrelapse,whichissupportedbythe
limiteddata.(See"Initialmanagementoflowriskgestationaltrophoblasticneoplasia",sectionon'Consolidation
therapy'.)
TheCharingCrossGrouphasreportedtheuseofinductionlowdoseetoposide(100mg/m2)andcisplatin(20
mg/m2)ondays1and2everysevendaysinselectedpatientswithhightumorburden.Thishasalmost
completelyeliminatedearlymortalityfromrespiratorycompromiseandhemorrhage.Theyalsoreporta94
percentremissionratewithEMACObycarefullyexcludingnongestationaltumorsusinggeneticanalysis[14].
PatientswithbrainmetastasesForpatientswithbrainmetastases,aneurosurgicalconsultshouldbe
obtainedpriortotreatment.Thesepatientsareatriskforcomplicationsdirectlyrelatedtotheirbrainmetastases
orasaconsequenceoftreatment,whichmayrequireurgentoremergenttreatment(eg,craniotomyfor
intracerebralbleeding).Forthesepatients,weadministeramodificationofsystemicEMACOthatusesa
higherMTXdose(1000mg/m2over24hours)thanwhatisroutinelyadministered[15].Thehigherdoseof
parenteralMTXallowsforadequatelevelsofMTXwithinthecerebrospinalfluid(CSF)[1518].Inaddition,these
patientsshouldreceivedexamethasonetodecreasecerebraledemahowever,prophylacticantiepilepticdrugs
aregenerallynotrecommendedinmostpatients,providedthereisnohistoryofanantecedentseizure.(See
"Seizuresinpatientswithprimaryandmetastaticbraintumors".)
Atypicalregimenisasfollows[18]:
Etoposide100mg/m2IVover60minutesondays1and2
MTX1000mg/m2IVover24hoursonday1
ActD0.5mgIVbolusondays1and2
Leucovorincalcium30mgintramuscular(IM)ororallyevery12hoursforthreedays,starting32hours
aftertreatmentwithMTX
Cyclophosphamide600mg/m2IVonday8
Vincristine1.0mg/m2IVonday8
Finally,thesepatientsshouldbecloselyfollowedduringtreatment,whichcanbedoneusingserialimaging.
RoleforintrathecaltherapyTheneedforintrathecal(IT)therapyinthesepatientsiscontroversial
[16,1820],anditsusealongsidehighdoseEMACOisbasedoninstitutionalpreferences.Ifadministered,MTX
isgivenasa12.5mgdoseITonday8,followedbyleucovorincalcium15mgat24and36hours.However,one
smallstudythatincluded15patientstreatedwithEMACOplusITMTXreportedthat87percent(13patients)
achievedasustainedremissionwithouttheuseofwholebrainirradiation[18].
ConcomitantwholebrainradiationtherapyAttheNewEnglandTrophoblasticDiseaseCenter
(NETDC),weadministercranialRT(20to30Gyin2Gydailyfractions)concurrentlywithhighdoseMTX
chemotherapy.AswiththeroleofITMTX,theroleofcranialRTisalsocontroversial.Inadditiontoshrinkingthe
brainmetastases,concomitantcranialirradiationincreasestheMTXconcentrationwithinthecentralnervous
system(CNS)[21]andreducestheriskofcerebralhemorrhagepriortoeradicationoftumor,andmayimprove
survival[22,23].However,theuseofconcurrentMTXandcranialirradiationalsoincreasedthelikelihoodof
treatmentrelatedtoxicity,especiallyleukoencephalopathy.(See"Delayedcomplicationsofcranialirradiation",
sectionon'Neurocognitiveeffects'.)
CisplatincontainingregimensInsomecenters,amodifiedEMACOregimenthatincorporates
cisplatinispreferentiallyadministeredtopatientswithariskscore>12.Themostcommonlyusedcombination
replacesvincristineandcyclophosphamide(usedinEMACO)withetoposideandcisplatinonday8(EMAEP).
EMAEPaloneorincombinationwithsurgeryinducedcompleteremissionin16(76percent)of21patientswith
EMACOresistance[5].
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WhilenorandomizedtrialscomparedEMACOwithcisplatincontainingregimens,aretrospectivestudy
evaluatedoutcomesamong83patientstreatedwithcisplatincontainingtreatmentand103patientstreatedwith
EMACO[24].ComparedwithEMACO,incorporationofcisplatinwasassociatedwith:
Aslightlylowerremissionrate(85versus92percent,respectively)
AlowernumberofcyclestoachieveanormalhCGlevel(threeversusfivecourses)
Moretoxicity,includingfever,nephropathy,nausea,anddiarrhea
APEGiventheactivityofcisplatinforGTN,onegroupreportedtheirexperienceusingActD,cisplatin,and
etoposide(APE)forhighriskGTNthatincluded59patients(outofatotalof96)whoweretreatedwiththis
regimenasinitialtherapybetween1985and2013[25].Patientswithbrainmetastasesorplacentalsite
trophoblastictumors(PSTT)wereexcludedfromtreatment.Theoverallremissionrateforthesepatientswas95
percent.Onepatientrequiredtreatmentdiscontinuationafterfourcyclesduetograde2ototoxicity.Thefinaltwo
hadrefractorydiseasetothisregimen,butallthreeenteredremissionwithsecondlineEMACOtherapy.The
fiveyeardiseasefreesurvivalratewas98percent.
SurgeryApproximately50percentofpatientswithhighrisk,metastaticGTNwillrequireadjuvantsurgeryto
achievecure,eveninthepresenceofmultiorganinvolvement[2639].Asanexample,inonestudyof50
patientswithhighrisk,metastaticGTNtreatedwithEMACObetween1986and2005,among24patientswho
underwentatotalof28surgicalprocedures,thecureratewas87.5percent.Theseproceduresincluded
hysterectomy,pulmonaryresection,uterinewedgeresection,smallbowelresection,andselectiveuterineartery
embolization[33].Surgeryisgenerallyperformedtoresectfociofchemotherapyresistantdiseaseortocontrol
complicationssuchasbleedingorinfection.
PLACENTALSITEOREPITHELIOIDTROPHOBLASTICTUMORAlthoughuniversallyacceptedguidelines
arenotavailable,patientswithplacentalsitetrophoblastictumor(PSTT)orepithelioidtrophoblastictumor(ETT)
shouldbetreatedwithacombinationofsurgeryandchemotherapy.Multiagentregimensareusually
administered,includingetoposide,methotrexate(MTX),plusactinomycinD(ActD)alternatingwith
cyclophosphamideandvincristine(EMACO)[40]orEMAplusetoposideandcisplatin(EMAEP)[41].There
arenoprospectivedatatoinformwhetheroneortheotheristhepreferredregimen.(See"Managementof
resistantorrecurrentgestationaltrophoblasticneoplasia",sectionon'Highriskgestationaltrophoblastic
neoplasia'.)
Unfortunately,patientswithmetastaticdiseasehaveapoorprognosisandahighfatalityrate[4244].Ina2012
reviewoftheliteraturethatreportedonthedeathsfromgestationaltrophoblasticneoplasia(GTN),30percent
hadplacentalsitetrophoblastictumors(PSTT)[44].Inaddition,onesingleinstitutionseriesof18patientswith
PSTTreportedthatfiveofsixwhohadextrauterinediseaseultimatelydieddespitetheadministrationofmulti
agentchemotherapy[43].SurvivalwithPSTTisstronglyrelatedtothenumberofyearssincetheantecedent
pregnancy.Papadopoulosetal,reportingon34patients,foundthatwhileall27patientsdiagnosedwithinfour
yearsoftheantecedentpregnancysurvived,allsevenpatientsdiedwhentheantecedentpregnancywasmore
thanfouryears[42].
MONITORINGDURINGTREATMENTAswithwomenwhoaretreatedforlowriskgestationaltrophoblastic
neoplasia(GTN),allwomenwithhighriskGTNshouldbemonitoredwithserialmeasurementsofserumhuman
chorionicgonadotropin(hCG)atthestartoftreatmentandthenatweeklyintervalsduringtherapy.Thisand
otherconsiderationsforpatientsduringtreatmentarediscussedseparately.(See"Initialmanagementoflow
riskgestationaltrophoblasticneoplasia",sectionon'Monitoringduringtreatment'.)
TheapproximatebiologichalflifeofhCGis1.5to3days,andserumlevelsshouldfallexponentially(byatleast
onelogwithin18days).Aslowerrateofdeclinesuggeststhepossibilityofchemoresistance,althoughthereis
noconsensusorclearguidelineastotheoptimalcutofffordeterminingchemoresistanceorthemanagementof
patientswithaslowerthanexpectedtumormarkerdecline[4547].
DefinitionofremissionRemissionisachievedwhenthequantitativehCGlevelbecomesundetectablefor
threeconsecutiveweeks.Giventhesensitivityofthistumormarker,noimagingisrequirediflevelsare
consistentwithremissionbecauseabnormalitiesonimagingcanpersistdespitetheattainmentofundetectable
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hCGlevels,representingfibrosisratherthanactivetumor.
PersistentorprogressivediseaseTheFrenchTrophoblasticDiseaseReferenceCenterinLyondefines
chemotherapyresistanceasanincreaseoraplateauintwoconsecutivehCGvaluesoveratwoweekinterval
[48].Asdescribedabove,othergenerallyacceptedcriteriaincludedetectionofnewmetastases[49].For
patientswhoappeartohavepersistentdisease,surgerymaybeacurativeoption.Theapproachtopatientswho
experiencediseaseprogressionisdiscussedseparately.(See"Gestationaltrophoblasticneoplasia:
Epidemiology,clinicalfeatures,diagnosis,staging,andriskstratification".)
PROGNOSISTheoverallcurerateforpatientswithhighriskgestationaltrophoblasticneoplasia(GTN)(stage
IItoIII)rangesbetween95and100percent[50].AttheNewEnglandTrophoblasticDiseaseCenter(NETDC),
wetreated90patientsbetweenJuly1965andDecember2013,ofwhom77.8percenthadasustainedcomplete
remissionwithprimarychemotherapy(table2).Asdepictedinthetable,ofthosewhodevelopedresistance,
secondlinetherapyultimatelyresultedinsustainedremissionin85percentofpatients.Overall,87(96.7
percent)of90patientswithhighriskstageIIandIIIGTNachievedcompleteremission.
ForpatientswithInternationalFederationofGynecologyandObstetrics(FIGO)stageIVhighriskGTN,the
prognosisisnotasgood,thoughcompleteremissioncanbeexpectedin60to70percentofpatients[50].
Muchofthissuccessisduetotheuseofcombinationchemotherapy.Aftercombinationchemotherapywas
introducedasprimarytreatmentinthisgroup,thesurvivalratedramaticallyimproved.Sincetheintroductionof
intensiveprimarycombinationchemotherapywithadjunctivesurgeryandradiationtherapy(RT),survivalatthe
NETDCincreasedfrom30to84percent(table3)[26].
PrognosticfactorsForpatientswithhighriskGTN,longtermsurvivalappearedtobeassociatedwith
variablesrelatedtodiseaseextent[51]:
Inthepresenceoflivermetastases,only27percentwerealive
Ifbrainmetastaseswerepresent,thesurvivalratewas70percent
Ifbothwerepresent,only10percentwerealive
DatafromtheCharingCrossHospitalindicatethatsurvivalwithhepaticmetastasesappearstohaveimproved
overtime.Excludingearlydeaths(withinfourweeksofpresentation)andtwodeathsunrelatedtoGTN,the
causespecificsurvivalin25patientswas68percent[52,53].
POSTTREATMENTSURVEILLANCEAfterremissionisachieved,serumhumanchorionicgonadotropin
(hCG)shouldbemeasuredmonthlyuntiltherehavebeenundetectablehCGlevelsfor12months[54,55].
Thefollowupofpatientstreatedforhighriskgestationaltrophoblasticneoplasia(GTN)issimilartothatof
womentreatedforlowriskGTNandincludesconsiderationsofcontraceptionandthetimingofsubsequent
pregnancies.Theseissuesarediscussedseparately.(See"Initialmanagementoflowriskgestational
trophoblasticneoplasia",sectionon'Posttreatmentsurveillance'and"Initialmanagementoflowriskgestational
trophoblasticneoplasia",sectionon'Fertilityandpregnancy'.)
UterinearteriovenousmalformationPatientstreatedforGTNthatinvadedthemyometrium(bothlowrisk
andhighrisk)areatriskofdevelopingauterinearterymalformation(alsoknownasanarteriovenousfistula),
whichcanpersistformonthsoryearsafterremissionisachieved.Afistulamayremainasymptomaticand
undiagnosedormaypresentwithmenorrhagia.Thepresenceofanarteriovenousmalformationhasalsobeen
associatedwithrecurrentmiscarriage.(See"Differentialdiagnosisofgenitaltractbleedinginwomen",section
on'Arteriovenousmalformation'.)
ThediagnosisismadewiththeuseofcolorDopplertransabdominalorendovaginalultrasonography.Selective
pelvicarteriographyclearlyidentifiestheabnormalvascularmalformationandhelpsinevaluatingpossible
treatmentmodalities.Ifsymptomatic,treatmentconsistsofhysterectomyor,whenpreservationofreproductive
functionisdesired,treatmentconsistsofselectiveuterinearteryembolization[5658].
DIAGNOSISOFRECURRENTORRESISTANTDISEASEPatientswhosehumanchorionicgonadotropin
(hCG)levelreelevatesafterbecomingundetectableforthreeconsecutiveweeksareconsideredtohave
recurrentdisease.Incontrast,patientswhosehCGlevelremainselevateddespitetreatmentareconsideredto
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haveresistantdisease.Despitethesuccessofcombinationchemotherapy,patientstreatedforhighrisk
gestationaltrophoblasticneoplasia(GTN)havean8to10percentriskofrecurrence,dependentonstageand
riskscore[59].ThisisoftendetectedbyareelevationinthequantitativeserumhCGlevelsafterthree
consecutiveweeksofundetectablequantitativehCGlevels.Theapproachtopatientswithrecurrentorresistant
diseaseisdiscussedseparately.(See"Gestationaltrophoblasticneoplasia:Epidemiology,clinicalfeatures,
diagnosis,staging,andriskstratification".)
SUMMARYANDRECOMMENDATIONS
Gestationaltrophoblasticneoplasia(GTN)ischaracterizedbytheInternationalFederationofGynecology
andObstetrics(FIGO)stageandtheWorldHealthOrganization(WHO)riskscore(table1).Patientsare
definedashavinghighriskGTNiftheyhavestageIVdiseaseorstageIItoIIIdiseasewithariskscore>6.
(See'Definitionofhighriskdisease'above.)
TheWHOPrognosticScoringSystemisnotapplicabletopatientswithplacentalsitetrophoblastictumor
(PSTT)orepithelioidtrophoblastictumor(ETT).Therefore,patientswiththesesubtypesofGTNarenot
categorizedaseitherlowriskorhighrisk.TheyshouldbecharacterizedbytheirFIGOStage.(See
'Definitionofhighriskdisease'above.)
GTNisuniquelysensitivetochemotherapy,whichisthemajortreatmentmodalityforpatientswithhigh
riskdisease.TheexceptiontothisiswomenwithPSTTorETT,inwhichcase,theprimarytreatmentmay
beacombinationofsurgeryandchemotherapy,primarilybecausePSTTandETTarerelativelyresistantto
chemotherapyascomparedwithchoriocarcinomaandinvasivemole.(See'Approachtotreatment'above.)
ForpatientswithhighriskGTN,werecommendmultiagentchemotherapyratherthansingleagent
therapy(Grade1B).Wesuggestacombinationofetoposide,methotrexate(MTX),plusactinomycinD
(ActD)alternatingwithcyclophosphamideandvincristine(EMACO)(Grade2C).(See'EMACO'above.)
ForpatientswithhighriskGTNandbrainmetastases,aneurosurgicalconsultshouldbeobtainedpriorto
treatment.WesuggestEMACOastheprimarysystemictreatment,usingahigherMTXdose(1000
mg/m2over24hours)thanwhatisroutinelyadministeredotherwise(Grade2C).Wealsosuggestcranial
radiationtherapy(RT)forthesepatients(Grade2C).However,forpatientswhodonotwishtoproceed
withcranialRT,wesuggestadditionalchemotherapyusingintrathecalMTX(Grade2C).(See'Patients
withbrainmetastases'above.)
Approximately50percentofpatientswithhighrisk,metastaticGTNwillrequireadjuvantsurgeryto
achievecure,eveninthepresenceofmultiorganinvolvement.(See'Surgery'above.)
Althoughuniversallyacceptedguidelinesarenotavailable,forpatientswithPSTTorETT,wesuggesta
combinationofsurgeryandchemotherapy(Grade2C).Multiagentregimensareusuallyadministered,
includingEMACOorEMAplusetoposideandcisplatin(EMAEP).Therearenoprospectivedatato
informwhetheroneortheotheristhepreferredregimen,andachoicebetweenthemisbasedon
institutionalpreferences.(See'Placentalsiteorepithelioidtrophoblastictumor'above.)
AswithwomenwhoaretreatedforlowriskGTN,allwomenwithhighriskGTNshouldbemonitoredwith
serialmeasurementsofserumhumanchorionicgonadotropin(hCG)atthestartoftreatmentandthenat
weeklyintervalsduringtherapy.(See'Monitoringduringtreatment'above.)
TheoverallcurerateforpatientswithhighriskGTN(stageIItoIII)rangesbetween95and100percent.
Theextentofdiseaseisaprognosticfactoramongthesepatients.(See'Prognosis'above.)
Afterremissionisachieved,serumhCGshouldbemeasuredmonthlyuntilmonitoringhasshownoneyear
ofnormalhCGlevels.(See'Posttreatmentsurveillance'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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Topic96232Version1.0
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GRAPHICS
FIGOStagingofGestationalTrophoblasticNeoplasia(GTN)and
modifiedWHOPrognosticScoringSystemasadaptedbyFIGO
Stage
I
Diseaseconfinedtothe
uterus
Stage
II
GTNextendsoutsideof
theuterus,butislimited
tothegenitalstructures
Stage
III
GTNextendstothelungs,
with
or
withoutgenitaltract
involvement
Stage
IV
Allothermetastaticsites
Thestageshouldbefollowed
bythesumoftheriskfactors
(eg,III:5)
Riskfactor
Score
Age(years)
<40
40
Antecedent
pregnancy
Mole
Abortion
Term
4to6
7to
>12
Interval
(months)*
12
Pretreatment
serumhCG
(mIU/mL)
<10 3
10 3to
10 4
10 4
to
10 5
>10 5
Largesttumor
<3cm
3to4
5cm
(including
uterus)
Siteof
metastases
Numberof
cm
Lung
Spleen,
kidney
GI
tract
Brain,
liver
1to4
5to8
>8
Single
drug
2
drugs
metastases
Priorfailed
chemotherapy
FIGO:InternationalFederationofGynecologyandObstetricsWHO:WorldHealthOrganization
hCG:humanchorionicgonadotropin.
*Interval(inmonths)betweenendofantecedentpregnancyandstartofchemotherapy.
Originalfiguremodifiedforthispublication.BerkowitzRS,GoldsteinDP.Currentmanagementof
gestationaltrophoblasticdiseases.GynecolOncol2009112:654.Tableusedwiththepermissionof
ElsevierInc.Allrightsreserved.
Graphic98185Version2.0
http://www.uptodate.com/contents/initialmanagementofhighriskgestationaltrophoblasticneoplasia?topicKey=ONC%2F96232&elapsedTimeMs=0&so
10/13
2/4/2015
Resultsofchemotherapyin90patientswithhighriskstageIIand
IIIgestationaltrophoblasticneoplasia(GTN)(NewEngland
TrophoblasticDiseaseCenter,July1965toDecember2013)
Stage
II
III
Total
Numberof
patients
Remissions(%)
16
16(100)
Primary
11
11(68.9)
Secondline
5(31.1)
74
71(95.9)
Primary
59
59(79.7)
Secondline
15
12(16.3)
90
87(96.7)
Primary
70
70(77.8)
Secondline
20
17(18.9)
Treatment
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Resultsofchemotherapyin39patientswithstageIVgestational
trophoblasticneoplasia(NewEnglandTrophoblasticDiseaseCenter,
July1965toDecember2013)
Timeperiod
Totalnumberof
patients
Remissions(%)
1965to1975
20
6(30)
1976to2013
19
16(84)
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Disclosures
Disclosures:RossSBerkow itz,MDNothingtodisclose.DonaldPeterGoldstein,MDNothingto
disclose.NeilSHorow itz,MDNothingtodisclose.BarbaraGoff,MDNothingtodisclose.DonS
Dizon,MD,FACPEmployeeofUpToDate,Inc.SandyJFalk,MD,FACOGEmployeeofUpToDate,Inc.
Contributordisclosuresarereview edforconflictsofinterestbytheeditorialgroup.Whenfound,these
areaddressedbyvettingthroughamultilevelreview process,andthroughrequirementsfor
referencestobeprovidedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofall
authorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy
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