Gynecologic Malignancies
J.BrianSzender31March2016
Outline
• FemaleCancerStatistics• UterineCancer• AdnexalCancer• CervicalCancer• VulvarCancer
Uterine CancerEndometrialCancerUterineSarcoma
Endometrial Cancer
• EpidemiologyandRiskFactors• Histology• Presentation• Diagnosis• Staging• Therapy
• Early• LocallyAdvanced• Metastatic• Recurrent
• Follow-Up• FutureTherapy
Epidemiology
• 60,500casesexpectedin2016• 25.3per100,000women
• 10,470deathsexpectedin2016
Epidemiology
IncreasedRisk
• Age• UnopposedEstrogens• Exogenous• Tamoxifen• Obesity
• GeneticRisk• LynchSyndrome• CowdenSyndrome
DecreasedRisk
• ProgestationalAgents• OralContraceptivePills• LevonorgestrelIUS
• PhysicalActivity• Pregnancy• Breastfeeding
Histology
• TypeI• Endometrioid,welldifferentiated• Lessaggressive• Usuallylocalized• GoodPrognosis
• TypeII• Clearcell,papillaryserous,MMMT,poorlydifferentiated• Moreaggressive• Likelytospread• WorsePrognosis
Histology – Molecular Features
TypeI
• Diploid• K-rasoverexpression• PTENmutations• Microsatelliteinstability
TypeII
• Aneuploid• K-rasoverexpression• P53overexpression
Clinical Presentation
• AbnormalUterineBleeding• PostmenopausalUterineBleeding• AbnormalVaginalDischarge• Endometrialcellsonapapsmear• Bloating/pelvicpressure/pain(ifadvanceddisease)
Diagnosis
• Ultrasound• EndometrialBiopsy• Hysteroscopy• DilationandCurettage
• Hysterectomy+/-BSO+/-Lymphnodesampling
wikipedia
Staging
Therapy – Early disease
Therapy – Locally advanced disease
Therapy – Metastatic disease
Therapy - Recurrence
• Re-excision• Radiation• SystemicTherapies:
Follow-up
• Regularpelvicexaminations• Symptomawareness• Noroleforroutineimaging/vaginalcytology
Emerging Therapies
• SentinelNodeMapping• FertilityPreservation• TargetedTherapies
Uterine Sarcoma
• EpidemiologyandRiskFactors• Histology• Presentation• Diagnosis/Staging• Therapy• Follow-Up• FutureTherapy
Epidemiology
• Medianagerangesis40sto50sbasedonhistologictype• Leiomyosarcomasaremorecommoninblackwomenthanwhitewomen(ageadjustedriskis1.5vs0.9per100,000)
Risk Factors
• Priorradiationexposure• Hormoneexposure• ESSistheonlytruecontraindicationtohormonereplacementaftersurgeryforagynecologicmalignancy
• TamoxifenUse• HereditaryPredisposition• HNPCC/Lynchsyndrome
Histology
• Leiomyosarcoma• Fleshy• NuclearAtypia• TumorNecrosis
• Endometrialstromalsarcoma• LowGrade• “Bland”• Singlemass• ER/PRpositive
Histology
• UndifferentiatedUterineSarcoma• VERYatypicalcells
Presentation
• Abnormalvaginalbleeding• Abdominopelvicmass• Incidentaldiagnosisatthetimeofhysterectomy
Diagnosis/Staging
Therapy
• EndometrialStromalSarcoma• Observation• HormonalTherapy• ConsiderRadiotherapy
• LMS/UUS• Chemotherapy• Radiotherapy
• Lotsofnegativetrials…disappointingresults• Mosttrialshaveslowaccrualduetorarityoftumors
Therapy
Follow-Up
• Recurrenceiscommon• Routineexams• RoutineCTscans• Patientsymptommonitoring
Emerging Therapies
• Continuedchemotherapytrials• Biologictherapies• Numerousgeneticmutationsinthesetumors• Targetedtherapies
• Anti-VEGF• Multi-kinaseinhibitors• mTORinhibitors
Adnexal CancersEpithelialTumorsGermCellTumorsStromalTumors
Epithelial Cancers (OV/FT/PP)
• EpidemiologyandRiskFactors• Histology• Presentation• Diagnosis• Staging• Therapy
• PrimaryDisease• Recurrent
• Follow-Up• FutureTherapy
Epidemiology
• 22,280casesexpectedin2016• 11.9per100,000women
• 14,240deathsexpectedin2016
Epidemiology
IncreasedRisk
• Age• FamilyHistory• BRCA• Lynch
• PID• Endometriosis• Smoking(mucinous)
DecreasedRisk
• OralContraceptivePills• TubalInterruption• Hysterectomy• Pregnancy• Breastfeeding• Lowfatdiet
Histology
• Serous• Mucinous• Endometrioid• ClearCell• TransitionalCell• Squamous• Undifferentiated• Carcinosarcoma
PNAS2011
Clinical Presentation
• Earlydiseaseisusuallyasymptomatic• Symptomsaregenerallybenignandnon-specific• Anorexia• Fatigue• Earlysatiety• Lossofappetite• Bloating• Diffuse/dull/constantabdominalpain
“Thecancerthatwhispers”
Diagnosis
• Ultrasound• CA125• CTforextentofdiseasespread• Paracentesis/thoracentesis
• Limitedroleforscreeningpatientsatpopulationrisk
• Surgicalevaluation
Staging
Nethealthbook.com
Therapy – Primary disease
Therapy – Recurrence
Follow-up
• Regularpelvicexaminations• MonitorCA125-controversial• Imagingforsymptoms(orelevatedCA125)• GENETICCOUNSELING/TESTING• CascadeTestingforfamilymembers• Clinicaltrials
Emerging Therapies
• Targetedtherapies• Cytotoxicagents• HIPEC• Alternatedosingschemes
• Vaccinetherapies• Revisitingradiotherapy
Germ Cell Tumors
• Epidemiology• Histology• Presentation• Diagnosis• Staging• Therapy
• Early• LocallyAdvanced• Metastatic• Recurrent
• Follow-Up• FutureTherapy
Epidemiology
• Approximately5%ofovariantumors• “JuvenileOvarianCancer”• Medianage16-20yearsdependingonhistology
• 10-yearsurvivalupto88.6%
Histology
• Dysgerminoma• Mostcommonmalignantovariangermcelltumor• 5-10%associatedwithgonadoblastomas• 10%bilateralongrossexamandanother10%havemicroscopicinvolvement
• YolkSacTumor(endodermalsinustumor)• Tan-gray• Abundanthemorrhageandnecrosis• AFPiselevated
Histology
• Choriocarcinoma• Rareasaprimarytumoroftheovary• Syncytiotrophoblast/cytotrophoblastadmixture• Spreadsbyvascularinvasion
• Teratomas• Maturecysticteratomas(Benign,“dermoids”)• Immature(malignant)teratomas=3%ofteratomas• Mostareunilateral
Presentation
• Abdominalpainassociatedwithapalpableabdominopelvicmass(85%ofpatients)• Acuteabdominalpain(10%)• Duetorupture,hemorrhage,ortorsion
• Abdominaldistension(35%)• Fever(10%)• Vaginalbleeding(10%)
Diagnosis
• Largemass,generallyfoundatthetimeofsurgery• Primarysurgeryisoftenrequiredfordiagnosisandtherapy(resolutionofsymptoms)• Fertilitypreservation:• removalofabnormalovaryandsamplingofotherpelvictissues• preferableifpossible(youngpatientages)
Staging
Nethealthbook.com
Therapy – Primary Setting
• Observationfor:• StageIGrade1immatureteratomas• StageIdysgerminoma
• Systemiccytotoxicchemotherapyforeveryoneelse• Bleomycin/Etoposide/Clisplatin(BEP)
• 5daysoftherapyevery3weeksfor3-4cycles• Etoposide/Carboplatin
• 3daysoftherapyevery3weeksfor3cycles• Selectedpatientsonlybasedonriskoftoxicityanddisease
Therapy – Recurrence
Borrowedfromtesticularcancerstudies
Follow-up
• PsychosocialSupport• Routineexams• Serumbiomarkers(ifindicated)
Emerging Therapies
• Clinicaltrials• Lessextensivesurgery• Lesscytotoxictreatment• Targetedtherapies
Stromal Tumors
• Epidemiology• Histology• Presentation• Diagnosis• Staging• Therapy
• Early• LocallyAdvanced• Metastatic• Recurrent
• Follow-Up• FutureTherapy
Epidemiology
• Accountfor7%ofmalignantovarianneoplasms• Accountfor90%offunctionaltumors• Annualincidencebetween0.5and1.7casesper100,000women
Histology
• GranulosaCellTumors• Estrogenproducing• Inhibinasabiomarker
• BisbetterthanA• Adulttype
• Lowgrade/indolent• Diagnosedlaterinlife
• Juveniletype• 44%diagnosedbeforeage10• Isosexualprecociouspuberty
Histology
• Thecoma/Fibroma• Lipid-ladenstromalcells• Occurlaterthanotherstromaltumors(mostin30s/40s)• Abnormalbleedingand/orapelvicmass
Histology• Stertoli-LeydigTumors• Lessthan0.2%ofovariantumors
• Androgenproducingtumorsleadingtovirilization
Presentation
• Abdominopelvicmass• Abnormalbleeding• Virilization(Sertoli-Leydigcelltumors)
Staging / Therapy / Follow-up
• Staging• Sameasotherovariantumors
• Therapy• Hybridofgermcellandepithelialcancers
• Follow-up• Routineexams• Serummarkersifappropriate
Cervical Cancer
Cervical Cancer
• EpidemiologyandRiskFactors• Histology• Presentation• Diagnosis• Staging• Therapy
• Early• LocallyAdvanced• Metastatic• Recurrent
• Follow-Up• FutureTherapy
Epidemiology
• 12,990casesexpectedin2016• 7.7per100,000women
• 4,120deathsexpectedin2016
Epidemiology
• HPVinfection• Highparity• Increasednumberofsexualpartners• Youngageattimeoffirstsexualintercourse• Lowsocioeconomicstatus• Historyofsmoking• Long-termuseoforalcontraceptives• Physicalinactivity
Histology
• Squamous• Adenocarcinoma• Rarehistologies• Clearcell• Serous• GlassyCell• Neuroendocrine• Mesenchymaltumors
Pathogenesis
JCI.org
Clinical Presentation
• Post-coitalbleeding• Abnormaluterinebleeding• AbnormalPapsmear• Pelvicpain• Flankpain• Uncontrolledleakageofurine/stoolfromvagina
Diagnosis
• Pelvicexamination/biopsies• Conebiopsy• Chestx-ray• IVP• Cystoscopy• Proctoscopy
Staging
http://dx.doi.org/10.1590/S0100-39842007000300014
• Clinicallystaged• PETCToftenusedin
westerncountriesbutnotavailableinthehighestprevalenceregionsoftheworld
Therapy
• StageIA1–Conebiopsy,hysterectomy• StageIA2–modifiedradicalhysterectomy• StageIBandIIA–radicalhysterectomyORpelvicRT• AddchemotherapytoRTinIB2andIIA2• CanaddtoRTinIB1andIIA1
• StageIIBtoIVA–pelvicRTwithchemotherapy• StageIVB–systemicchemotherapy/clinicaltrials
Follow-up
• PsychosocialSupport• Routineexams• Cytologictesting
Emerging Therapies
• SentinelNodeMapping• FertilityPreservation• TargetedTherapies
Vulvar Cancer
Vulvar Cancer
• EpidemiologyandRiskFactors• Histology• Presentation/Diagnosis• Staging• Therapy• Early• LocallyAdvanced• Metastatic
• Follow-Up
Epidemiology
• 5,950casesexpectedin2016• 1,110deathsexpectedin2016
Epidemiology
• Condyloma• Historyofsquamousdysplasia• HPVinfectioninbasaloidorwartytypes• Commonriskfactorswithcervicalcancer• Multiplesexpartners• Earlyageatinitiationofsexualintercourse• HistoryofabnormalPapsmears
• HPVassociatedmorecommoninwomen<50years• Non-HPVismorecommoninolderwomen
Histology
Presentation – Early disease
PersistentIrritationDiscolorationBleeding
Presentation – Late disease
PainBleedingPressurefromenlargedmassesFoulodor
Staging
Staging
Therapy – Early
• Localexcision(simpleorradical)
Therapy – Locally Advanced
Therapy – Metastatic
• Systemiccytotoxictherapyisdisappointing• Targetedtherapiesareunderdevelopment
Follow-up
• PsychosocialSupport• Routineexams
Summary
• Riskcanbereducedbymodifyingriskfactors• Mostcancersareresponsivetofront-linetherapy• Managementofrecurrentdiseasevariesbysiteoforigin/histologybutisoftensub-optimal• Morediscoveriesareneededtoovercomethesediseases
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