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EndometrialCancerOB/GYNHospitalFudanUniversityXinLU,MD,Ph.D.EndometrialCancerOB/GYNHospi1Endometriodcancer---ContentsIncidenceRiskfactorsClassificationSymptomsPathologyFIGOStagingDiagnosisTreatmentEndometriodcancer---ContentsI2WHOCancerReportGlobalcancerratescouldincreaseby50%to15millionby2020Endometrialcanceristhe4thmostcommoncancerinwomenNewDiagnosedcases:142,000Diedcaseseachyear:42,000incidence~2-3%Averageage:60sWHOCancerReportGlobalcancer3HistologicTypesEndometrialCancersEndometrioid(87%)Adenosquamous(4%)PapillarySerous(3%)ClearCell(2%)Mucinous(1%)Other(3%)HistologicTypesEndometrialCa4
EndometrialCancer:TypeI/IITypeIEstrogenRelatedYoungerandheavierpatientsLowgradeBackgroundofHyperplasiaPerimenopausalExogenousestrogenFamilial/genetic(~15%)LynchIIsyndrome/HNPCCFamilialtrendTypeII(~10%)AggressiveHighgradeUnfavorableHistologyUnrelatedtoestrogenstimulationOccursinolder&thinnerwomenEndometrialCancer:TypeI/IIT5EndometrialCancer:RiskFactorsRiskFactorsRelativeRisk[X]
Obesity2-5
PCOS＞5Estrogenuse10-20Nulliparous3Infertility2-3Diabetes/Hypertension1.3-3Nulliparous3EarlyMenarche(<12y/o)1.5-2AtypicalHyperplasiaOC0.3-0.5From:WilliamsGynecology2009EndometrialCancer:RiskFact6EndometriumCarcinoma
2009Classification
StageCharacteristicStageI*TumorconfinedtothecorpusuteriIA*NoorlessthanhalfmyometrialinvasionIB*InvasionequaltoormorethanhalfofthemyometriumStageII*Tumorinvadescervicalstroma,butdoesnotextendbeyondtheuterus**StageIII*Localand/orregionalspreadofthetumorIIIA*Tumorinvadestheserosaofthecorpusuteriand/oradnexae#IIIB*Vaginaland/orparametrialinvolvement#IIIC*Metastasestopelvicand/orpara-aorticlymphnodes#.IIIC1*•PositivepelvicnodesIIIC2*•PositiveparaaorticlymphnodeswithorwithoutpositivepelviclymphnodesStageIV*Tumorinvadesbladderand/orbowelmucosa,and/ordistantmetastasesIVA*Tumorinvasionofbladderand/orbowelmucosaIVB*Distantmetastases,includingintra-abdominalmetastasesand/oringuinallymphnodes
EndometriumCarcinoma
2009Cla7StageI(73%)ConfinedtouterusStageII(11%)CervixinvolvedStageIII(13%)Uterineserosa,adnexae,positivecytology,vaginalmetastases,pelvic/aorticnodemetastasesStageIV(3%)Bladder,bowel,inguinalnode,distantmetastasisEndometrialCancer:FIGOSurgicalStageStageIConfinedtouterusStage8EndometrialCancerPrognosis:SurvivalbyStage:Stage%5yrsurvivalIA91IB88IC81IIA77IIB67IIIA60IIIB41IIIC32IVA20IVB5SurvivalbyGrade:Grade%5yrsurvival192287374Overall5YrSurvival84%StageandGradearethemostimportantprognosticfactorsAlteredoncogene/tumorsuppressorgeneexpressionisnowbeingevaluated(molecularstagingconcept)EndometrialCancerPrognosis:S9AggressiveHistologicSubtypes(Clear-cell,Serous)Increasingage(over65)VascularinvasionAneuploidyAlteredoncogene/tumorsuppressorgeneexpression(“molecularstaging”concept-p53,PTEN,microsatelliteinstability,MDR-1,HER2/neu,ER/PR,Ki67,PCNA,CD31,EGF-R,MMRgenes)Race?EndometrialCancer:PoorPrognosticFactorsAggressiveHistologicSubtypes10MolecularGeneticsPTENmutations:32%Tumorsuppressorgene(chrom10)PhosphataseEarlyeventincarcinogenesisAssociatedwith:endometrioidhistologyearlystagefavorablesurvivalMolecularGeneticsPTENmutatio11MolecularGeneticsp53tumorsuppressorgeneCellcycleandapoptosisregulationMostcommonlymutatedgeneinhumancancersOverexpression(markerformutation)Associatedwithpoorprognosisearlystage: 10%havep53mutationadvancedstage:50%havep53mutationnotfoundinhyperplasiaslateeventincarcinogenesisMolecularGeneticsp53tumorsu12GeneticSyndromes:HNPCC
HereditaryNon-PolyposisColonCancerLynchIISyndromeAutosomaldominantinheritanceMMR(mismatchrepair)mutationsGeneticinstabilityleadstoerror-proneDNAreplicationhMSH2(chrom2)hMLH1(chrom3)EarlyageofcolonCa:mean45.2yearsEndometrialCa:secondmostcommonmalignancy20%cumulativeincidencebyage70EarlierageofonsetthansporadiccasesOther:ovary(3.5-8fold),stomach,smallbowel,pancreas,biliarytractGeneticSyndromes:HNPCC
Here13Diagnosisofdisease:PatientAwareness*Morethan95%ofpatientswithEndometrialCancerreporthavingsymptomsPostmenapausalbleedingMenorrhagiaMetrorrhagiaBloodyDischargeEndometrialbiopsyisthemaindiagnostictoolperformedeitherintheofficeorviaD&CinORDiagnosisofdisease:Patient14UterineCancer:
Diagnosis/ScreeningPatientSymptoms/Awareness*Cytology–NotasatisfactoryscreeningtestSonography–NotCosteffectiveHysteroscopy–NotCosteffectiveHistology–Secondarytosymptoms(notasascreeningtest)UterineCancer:
Diagnosis/Scre15EndometrialCancer:
TransvaginalUltrasoundScreeningEndometrialCancer:
Transvagin16EndometrialCancer:
TransvaginalUltrasoundScreeningEndometrialCancer:
Transvagin17EndometrialCancer:
TransvaginalUltrasoundScreeningEndometrialCancer:
Transvagin18Normalendometrialstripe:Postmenopausal 4-8mmPostmenopausalonHRT 4-10mmU/SforDetectionofanyuterinepathologySensitivity: 85-95%Specificity: 60-80%PPV2-10%NPV99%Summary:EndometrialCancer:
TransvaginalUltrasoundScreeningNormalendometrialstripe:Summ19Hysteroscopy–NotsatisfactoryforscreeningtestStudiesoftheefficacyofhysteroscopyasadiagnostictoolvarywidelySensitivityreportedrangingfrom60-95%comparedtoD&CobtainedatthesametimeSpecificity50-99%Hysteroscopy–Notsatisfactor20妇产科课件子宫内膜癌英文21HysteroscopyandPositiveCytology?Studieshavebeenmixed:SomestudiessuggestanincreaseinpositiveperitonealcytologyseenatstaginglaparotomyinpatientswhohavehadhysteroscopyOtherstudieshavefailedtofindadifferenceinpositivecytologyinpatientsdiagnosedviahysteroscopyascomparedtoofficebiopsyorD&CHysteroscopyandPositiveCyto22Hysteroscopy–NotsatisfactoryToomuchcostandrisktobeusedasascreeningtest.Usefulforevaluationofabnormaluterinebleedingwhereofficebiopsyisunrevealing.UseinconjunctionwithuterinecurettageUsefultoseeandresectpolypsandsmallsubmucousfibroidsUsefultoperformdirectedbiopsyofsmalllesions.Hysteroscopy–Notsatisfactor23EndometrialCancer:
WhoNeedsanEndometrialBiopsy?PostmenopausalbleedingPerimenopausalintermenstrualbleedingAbnormalbleedingwithhistoryofanovulationPostmenopausalwomenwithendometrialcellsonPapThickenedendometrialstripeviasonographyEndometrialCancer:
WhoNeeds24SamplingoftheEndometriumOfficebiopsyprocedures(Pipelle,Vabraaspirator,Karmancannula)willagreewithaD&CperformedintheOR~95%ofthetimeOfficebiopsyhasa16%falsenegativeratewhenthelesionisinapolyporthecancercoverslessthan50%oftheendometriumGuidoetal.JReprodMed.1995;40:553PatientswithpersistentPMBafternegativeofficebiopsyshouldhaveD&C(+/-hysteroscopy)D&CisthegoldstandardsamplingmethodpreoperativeD&Cwillagreewithdiagnosisathysterectomy94%ofthetimeSamplingoftheEndometriumOff25妇产科课件子宫内膜癌英文26妇产科课件子宫内膜癌英文27妇产科课件子宫内膜癌英文28TreatmentforEndometrialHyperplasiawithoutatypia:ProgestintherapycontinuousorcyclicalChildbearingage:ProgestindominantOCPsorDepo-Provera150mgIMq3monthsorProvera10mgpo10days/monthandMayfollowwithovulationinductionafternormalbiopsyifpregnancydesiredPeriorPostmenopausal:Provera20mgpo10days/monthorDepo-Provera200mgIMq2monthsRepeatbiopsyin3-4monthsTreatmentforEndometrialHype29TreatmentforAtypicalEndometrialHyperplasia:23%riskofprogressiontocarcinoma(over10years)ifuntreated.Standardtreatmentwhenchildbearingiscompleteistotalhysterectomy(abdominalorvaginal)Frozensectiontoruleoutcarcinoma(upto20%havecoexistingendometrialcancer)TreatmentforAtypicalEndomet30TreatmentforAtypicalEndometrialHyperplasia:Conservativemedicaltherapycanbeattemptedinyoungerpatientswhorequestpreservationoffertility.D&CpriortoinitiationofmedicaltherapytoruleoutcarcinomaMegace40-80mg/day,Norethindroneacetate5mg/dayConservativetherapymayalsobeattemptedinyoungpatientswithearly,welldifferentiatedendometrialcarcinomas.Megace120-200mg/day,Norethindroneacetate5-10mg/dayTreatmentforAtypicalEndomet31Endometroidcarcinoma,GradingFIGO -Gr1-<5%solidtumor -Gr2-6%-50%solid -Gr3->50%solidtumorNUCLEARGRADESize,shape,stainingandchromatin,variability,prominentnucleoli.HighnucleargradeaddsonepointtoFIGOgradeEndometroidcarcinoma,Grading32CA125ChestX-rayMammogramsColonEvaluationOthersasindicatedUterineCancer:Pre-opEvaluationCA125UterineCancer:Pre-opEv33UterineCancer:Pre-opEvaluationTransvaginalU/S?CTScan?MRI?UterineCancer:Pre-opEvaluat34UterineCancer:Pre-opEvaluationUterineCancer:Pre-opEvaluat35UterineCancer:SurgicalStagingPreoperativepreparationAntimicrobialprophylaxisDVTprophylaxisSteepTrendelenburgLonginstrumentsavailableUterineCancer:SurgicalStagi36Availabilityoffrozensectiontodeterminetheextentofstagingprocedure.CapabilityofcompletesurgicalstagingCapabilityoftumorreductionifindicatedEndometrialCancer:Intra-operativeSurgicalPrincipalsAvailabilityoffrozensection37EndometrialCancer:SurgicalApproachTAH-BSO/washingsonlyEndometrioid*Grades1and<50%myometrialinvasion*orGrade2andnoorminimalinvasionand<2cmtumordiameter**VerifiedviafrozensectionEndometrialCancer:SurgicalA38EndometrialCancer:SurgicalApproachCompleteSurgicalStaging*AllGrade3Any>50%myometrialinvasionAny>2cmtumordiameterAllSerous/clearcellsubtype**Preoperativeassessmentofadvanceddisease(grosscervicalorvaginaldz,etc)*TAH-BSO,washings,lymphadenectomy**omental/peritonealbiopsyEndometrialCancer:SurgicalA39EndometrialCancer:AdjuvantTherapyBrachytherapyExternalbeamradiotherapyHormonaltherapyCytotoxicchemotherapyCombinationtherapyEndometrialCancer:AdjuvantT40EndometrialCancer:RecurrencePelvicexaminationPapsmearsCA125(high-risk)ChestX-ray(high-risk)EndometrialCancer:Recurrence41EndometrialCancer:SiteofRecurrence
InRadiatedPatientsSite%Distant65Pelvicanddistant15Pelvisonly15Vagina5EndometrialCancer:SiteofRe42EndometrialCancer:Follow-Up75-95%ofrecurrencesareinfirst36months60%ofpatientshavesymptoms(pain,wgtloss,vaginalbleeding)Raretocuredistantrecurrences50%vaginalrecurrencescuredEndometrialCancer:Follow-Up743EndometrialCancerOB/GYNHospitalFudanUniversityXinLU,MD,Ph.D.EndometrialCancerOB/GYNHospi44Endometriodcancer---ContentsIncidenceRiskfactorsClassificationSymptomsPathologyFIGOStagingDiagnosisTreatmentEndometriodcancer---ContentsI45WHOCancerReportGlobalcancerratescouldincreaseby50%to15millionby2020Endometrialcanceristhe4thmostcommoncancerinwomenNewDiagnosedcases:142,000Diedcaseseachyear:42,000incidence~2-3%Averageage:60sWHOCancerReportGlobalcancer46HistologicTypesEndometrialCancersEndometrioid(87%)Adenosquamous(4%)PapillarySerous(3%)ClearCell(2%)Mucinous(1%)Other(3%)HistologicTypesEndometrialCa47
EndometrialCancer:TypeI/IITypeIEstrogenRelatedYoungerandheavierpatientsLowgradeBackgroundofHyperplasiaPerimenopausalExogenousestrogenFamilial/genetic(~15%)LynchIIsyndrome/HNPCCFamilialtrendTypeII(~10%)AggressiveHighgradeUnfavorableHistologyUnrelatedtoestrogenstimulationOccursinolder&thinnerwomenEndometrialCancer:TypeI/IIT48EndometrialCancer:RiskFactorsRiskFactorsRelativeRisk[X]
Obesity2-5
PCOS＞5Estrogenuse10-20Nulliparous3Infertility2-3Diabetes/Hypertension1.3-3Nulliparous3EarlyMenarche(<12y/o)1.5-2AtypicalHyperplasiaOC0.3-0.5From:WilliamsGynecology2009EndometrialCancer:RiskFact49EndometriumCarcinoma
2009Classification
StageCharacteristicStageI*TumorconfinedtothecorpusuteriIA*NoorlessthanhalfmyometrialinvasionIB*InvasionequaltoormorethanhalfofthemyometriumStageII*Tumorinvadescervicalstroma,butdoesnotextendbeyondtheuterus**StageIII*Localand/orregionalspreadofthetumorIIIA*Tumorinvadestheserosaofthecorpusuteriand/oradnexae#IIIB*Vaginaland/orparametrialinvolvement#IIIC*Metastasestopelvicand/orpara-aorticlymphnodes#.IIIC1*•PositivepelvicnodesIIIC2*•PositiveparaaorticlymphnodeswithorwithoutpositivepelviclymphnodesStageIV*Tumorinvadesbladderand/orbowelmucosa,and/ordistantmetastasesIVA*Tumorinvasionofbladderand/orbowelmucosaIVB*Distantmetastases,includingintra-abdominalmetastasesand/oringuinallymphnodes
EndometriumCarcinoma
2009Cla50StageI(73%)ConfinedtouterusStageII(11%)CervixinvolvedStageIII(13%)Uterineserosa,adnexae,positivecytology,vaginalmetastases,pelvic/aorticnodemetastasesStageIV(3%)Bladder,bowel,inguinalnode,distantmetastasisEndometrialCancer:FIGOSurgicalStageStageIConfinedtouterusStage51EndometrialCancerPrognosis:SurvivalbyStage:Stage%5yrsurvivalIA91IB88IC81IIA77IIB67IIIA60IIIB41IIIC32IVA20IVB5SurvivalbyGrade:Grade%5yrsurvival192287374Overall5YrSurvival84%StageandGradearethemostimportantprognosticfactorsAlteredoncogene/tumorsuppressorgeneexpressionisnowbeingevaluated(molecularstagingconcept)EndometrialCancerPrognosis:S52AggressiveHistologicSubtypes(Clear-cell,Serous)Increasingage(over65)VascularinvasionAneuploidyAlteredoncogene/tumorsuppressorgeneexpression(“molecularstaging”concept-p53,PTEN,microsatelliteinstability,MDR-1,HER2/neu,ER/PR,Ki67,PCNA,CD31,EGF-R,MMRgenes)Race?EndometrialCancer:PoorPrognosticFactorsAggressiveHistologicSubtypes53MolecularGeneticsPTENmutations:32%Tumorsuppressorgene(chrom10)PhosphataseEarlyeventincarcinogenesisAssociatedwith:endometrioidhistologyearlystagefavorablesurvivalMolecularGeneticsPTENmutatio54MolecularGeneticsp53tumorsuppressorgeneCellcycleandapoptosisregulationMostcommonlymutatedgeneinhumancancersOverexpression(markerformutation)Associatedwithpoorprognosisearlystage: 10%havep53mutationadvancedstage:50%havep53mutationnotfoundinhyperplasiaslateeventincarcinogenesisMolecularGeneticsp53tumorsu55GeneticSyndromes:HNPCC
HereditaryNon-PolyposisColonCancerLynchIISyndromeAutosomaldominantinheritanceMMR(mismatchrepair)mutationsGeneticinstabilityleadstoerror-proneDNAreplicationhMSH2(chrom2)hMLH1(chrom3)EarlyageofcolonCa:mean45.2yearsEndometrialCa:secondmostcommonmalignancy20%cumulativeincidencebyage70EarlierageofonsetthansporadiccasesOther:ovary(3.5-8fold),stomach,smallbowel,pancreas,biliarytractGeneticSyndromes:HNPCC
Here56Diagnosisofdisease:PatientAwareness*Morethan95%ofpatientswithEndometrialCancerreporthavingsymptomsPostmenapausalbleedingMenorrhagiaMetrorrhagiaBloodyDischargeEndometrialbiopsyisthemaindiagnostictoolperformedeitherintheofficeorviaD&CinORDiagnosisofdisease:Patient57UterineCancer:
Diagnosis/ScreeningPatientSymptoms/Awareness*Cytology–NotasatisfactoryscreeningtestSonography–NotCosteffectiveHysteroscopy–NotCosteffectiveHistology–Secondarytosymptoms(notasascreeningtest)UterineCancer:
Diagnosis/Scre58EndometrialCancer:
TransvaginalUltrasoundScreeningEndometrialCancer:
Transvagin59EndometrialCancer:
TransvaginalUltrasoundScreeningEndometrialCancer:
Transvagin60EndometrialCancer:
TransvaginalUltrasoundScreeningEndometrialCancer:
Transvagin61Normalendometrialstripe:Postmenopausal 4-8mmPostmenopausalonHRT 4-10mmU/SforDetectionofanyuterinepathologySensitivity: 85-95%Specificity: 60-80%PPV2-10%NPV99%Summary:EndometrialCancer:
TransvaginalUltrasoundScreeningNormalendometrialstripe:Summ62Hysteroscopy–NotsatisfactoryforscreeningtestStudiesoftheefficacyofhysteroscopyasadiagnostictoolvarywidelySensitivityreportedrangingfrom60-95%comparedtoD&CobtainedatthesametimeSpecificity50-99%Hysteroscopy–Notsatisfactor63妇产科课件子宫内膜癌英文64HysteroscopyandPositiveCytology?Studieshavebeenmixed:SomestudiessuggestanincreaseinpositiveperitonealcytologyseenatstaginglaparotomyinpatientswhohavehadhysteroscopyOtherstudieshavefailedtofindadifferenceinpositivecytologyinpatientsdiagnosedviahysteroscopyascomparedtoofficebiopsyorD&CHysteroscopyandPositiveCyto65Hysteroscopy–NotsatisfactoryToomuchcostandrisktobeusedasascreeningtest.Usefulforevaluationofabnormaluterinebleedingwhereofficebiopsyisunrevealing.UseinconjunctionwithuterinecurettageUsefultoseeandresectpolypsandsmallsubmucousfibroidsUsefultoperformdirectedbiopsyofsmalllesions.Hysteroscopy–Notsatisfactor66EndometrialCancer:
WhoNeedsanEndometrialBiopsy?PostmenopausalbleedingPerimenopausalintermenstrualbleedingAbnormalbleedingwithhistoryofanovulationPostmenopausalwomenwithendometrialcellsonPapThickenedendometrialstripeviasonographyEndometrialCancer:
WhoNeeds67SamplingoftheEndometriumOfficebiopsyprocedures(Pipelle,Vabraaspirator,Karmancannula)willagreewithaD&CperformedintheOR~95%ofthetimeOfficebiopsyhasa16%falsenegativeratewhenthelesionisinapolyporthecancercoverslessthan50%oftheendometriumGuidoetal.JReprodMed.1995;40:553PatientswithpersistentPMBafternegativeofficebiopsyshouldhaveD&C(+/-hysteroscopy)D&CisthegoldstandardsamplingmethodpreoperativeD&Cwillagreewithdiagnosisathysterectomy94%ofthetimeSamplingoftheEndometriumOff68妇产科课件子宫内膜癌英文69妇产科课件子宫内膜癌英文70妇产科课件子宫内膜癌英文71TreatmentforEndometrialHyperplasiawithoutatypia:ProgestintherapycontinuousorcyclicalChildbearingage:ProgestindominantOCPsorDepo-Provera150mgIMq3monthsorProvera10mgpo10days/monthandMayfollowwithovulationinductionafternormalbiopsyifpregnancydesiredPeriorPostmenopausal:Provera20mgpo10days/monthorDepo-Provera200mgIMq2monthsRepeatbiopsyin3-4monthsTreatmentforEndometrialHype72TreatmentforAtypicalEndometrialHyperplasia:23%riskofprogressiontocarcinoma(over10years)ifuntreated.Standardtreatmentwhenchildbearingiscompleteistotalhysterectomy(abdominalorvaginal)Frozensectiontoruleoutcarcinoma(upto20%havecoexistingendometrialcancer)TreatmentforAtypicalEndomet73TreatmentforAtypicalEndometrialHyperplasia:Conservativemedicaltherapycanbeattemptedinyoungerpatientswhorequestpreservationoffertility.D&CpriortoinitiationofmedicaltherapytoruleoutcarcinomaMegace40-80mg/day,Norethindroneacetate5mg/dayConservativetherapymayalsobeattemptedinyoungpatientswithearly,welldifferentiatedendometrialcarcinomas.Megace120-200mg/day,Norethindroneacetate5-10mg/dayTreatmentforAtypicalEndomet74Endometroidcarcinoma,Gra
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