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Gynecologic Malignancies J. Brian Szender 31 March 2016

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  • 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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