NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)VulvarCancerVersion2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/28/202211:53:31AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ancerdex*NadeemR.Abu-Rustum,MDΩ/ChairMemorialSloanKetteringCancerCenter*CatherynM.Yashar,MD§/ViceChairUCSanDiegoMooresCancerCenterRebeccaArend,MDΩO'NealComprehensiveCancerCenteratUABKristinBradley,MD§UniversityofWisconsinCarboneCancerCenterRebeccaBrooks,MDΩUCDavisComprehensiveCancerCenterSusanaM.Campos,MD,MPH,MS?Dana-Farber/BrighamandWomen’sCancerCenterJunzoChino,MD§DukeCancerInstituteHyeSookChon,MDΩMoffittCancerCenterChristinaChu,MDΩFoxChaseCancerCenterMartaAnnCrispens,MDΩVanderbilt-IngramCancerCenterShariDamast,MD§YaleCancerCenter/SmilowCancerHospitalChristineM.Fisher,MD,MPH§UniversityofColoradoCancerCenterNCCNShailiAggarwal,PhDNicoleMcMillian,MSesPanelDisclosuresPeterFrederick,MDΩRoswellParkComprehensiveCancerCenterTriciaFredericks,MD,MPHΩFred&PamelaBuffettCancerCenterDavidK.Gaffney,MD,PhD§HuntsmanCancerInstituteattheUniversityofUtahRobertGiuntoliII,MDΩAbramsonCancerCenterattheUniversityofPennsylvaniaErnestHan,MD,PhDΩCityofHopeNationalMedicalCenterBrookeHowitt,MD≠StanfordCancerInstituteJayanthiLea,MDΩUTSouthwesternSimmonsComprehensiveCancerCenterAndreaMariani,MDΩMayoClinicCancerCenterKatherineMoxley,MD,MSΩUniversityofMichiganRogelCancerCenterDavidMutch,MDΩSitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineChristaNagel,MDΩTheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandSoloveResearchInstituteLarissaNekhlyudov,MD,MPHTDana-Farber/BrighamandWomen’sCancerCenterMirnaPodoll,MD≠Vanderbilt-IngramCancerCenterRituSalani,MD,MBAΩUCLAJonssonComprehensiveCancerCenterJohnSchorge,MDΩSt.JudeChildren'sResearchHospital/TheUniversityofTennesseeHealthScienceCenterRachelSisodia,MDΩMassachusettsGeneralHospitalCancerCenterPamelaSoliman,MD,MPHΩTheUniversityofTexasMDAndersonCancerCenterStefanieUeda,MDΩUCSFHelenDillerFamilyComprehensiveCancerCenterRenataUrban,MDΩFredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceStephanieL.Wethington,MD,MScΩTheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsEmilyWyse￥tientAdvocateKristineZanotti,MDΩCaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussigCancerInstituteΩGynecologiconcologyTInternalmedicine?Medicaloncology≠Pathology￥Patientadvocacy§Radiotherapy/Radiationoncology*DiscussionSectionWritingCommitteeVersion2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/28/202211:53:31AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ancerdexVULVOVAGINALMELANOMASUBCOMMITTEEUterinePanelDMBASubcommitteeLeadeCancerCenterRAbuRustumMDloanKetteringCancerCenterChristinaChu,MDΩerCenterDavidK.Gaffney,MD,PhD§HuntsmanCancerInstituteattheUniversityofUtahDavidMutch,MDΩSitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicinePamelaSoliman,MD,MPHΩTheUniversityofTexasMDAndersonCancerCenterCatherynM.Yashar,MD§UCSanDiegoMooresCancerCenteranelGenevieveBoland,MD,PhD?MassachusettsGeneralHospitalCancerCenterGiorgosKarakousis,MD?AbramsonCancerCenterattheUniversityofPennsylvaniaKariKendra,MD,PhD?TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandSoloveResearchInstituteMerrickI.Ross,MD?TheUniversityofTexasMDAndersonCancerCenterJosephSkitzki,MD?RoswellParkhensiveCancerCenterSusanM.Swetter,MD?StanfordCancerInstituteJohnA.Thompson,MD??FredHutchinsonCancerResearchCenter/SeattleCancerCareAlliance?DermatologyΩGynecologiconcology?Hematology/Hematologyoncology?Medicaloncology§Radiotherapy/Radiationoncology?Surgery/SurgicaloncologyVersion2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/28/202211:53:31AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ancerdexlievesthatthebestlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceanddationsotherwisedNCategoriesofEvidenceensusNCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.aryoftheGuidelinesUpdatesSquamousCellCarcinomaorAdenocarcinomaWorkup(VULVA-1)rRiskFactorsVULVAdalStatusVULVALimitedtotheVulvaVULVAorDistantRecurrenceVULVAAFVulvovaginalMelanomaClinicalPresentation;Workup;PrimaryTreatment;AdjuvantTreatment(VM-1)Follow-up/Surveillance;TreatmentforRecurrence(VM-2)PrinciplesofRadiationTherapy(VM-A)TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2022.Version2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/28/202211:53:31AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ancerdexeNCCNGuidelinesforVulvarCancerfromVersioninclude?GeneralChangespTheGuidelinenamewasrevisedasfollows:"VulvarCancer(SquamousCellCarcinoma)pAnewalgorithmforthetreatmentofvulvovaginalmelanoma(includescutaneousvulvarmelanomaandmucosalvulvovaginalmelanoma)wasadded(VM-1)?Workup:Newbulletadded,Considersomaticmutationaltestingforvulvarmelanomaandmucosalvulvovaginalmelanomaasclinicallyindicated(ie,BRAF,KIT)?Secondcolumn:Pathwayrevised,Squamouscellcarcinomaoradenocarcinoma?Footnotearevised:SeePrinciplesofPathology(VULVA-A).Ifvulvovaginalmelanomaissuspected,seePrinciplesofBiopsyandPathology(ME-B)intheNCCNGuidelinesforMelanoma:Cutaneous.?Footnotebrevised:SeePrinciplesofImaging(VULVA-B).Ifvulvovaginalmelanomaissuspected,SeePrinciplesofImaging(ME-D)intheNCCNGuidelinesforMelanoma:Cutaneous)?Footnotecrevised:ConsiderHIVtesting,especiallyinyoungerpatientssuspectedofhavingsquamouscellcarcinomaofthevulvaorotherHPV-relateddisease.PatientswithvulvarcancerandHIV...UpdatesinVersion1.2022oftheNCCNGuidelinesforVulvarCancerfromVersion3.2021include:VULVA-8icSurvivorshipsocialeffectsrevisedPsychosocialeffectsaftercancericSurvivorshipsocialeffectsrevisedPsychosocialeffectsaftercancerinpatientswhohavereceivedpelvicradiation.epsychologicalepsychologicalegdepressionanxietyfearofecurrencealteredbodyimagefinancialegreturntoworkranceconcernsranceconcernsandorinterpersonalegrelationshipsalityintimacyeffectsinnaturepnonalityintimacyeffectsinnaturenicalapproachpSentencerevised:"...HPV-independentSCCusuallynicalapproachp1stbullet:"...focusesonmanagingchronicdiseasemanagement,p1stbullet:"...focusesonmanagingchronicdiseasemanagement,monitoringofcardiovascularriskfactors,providingrecommendedvaccinations..."p2ndbullet:"...physicalexamination,andconductprovideanynecessaryimagingand/orlaboratorytesting.Allwomenpatients,whethersexuallyactiveornot,shouldbeaskedaboutgenitourinarysymptoms,includingvulvovaginaldryness..."pNewbulletadded:Forpremenopausalpatients,hormonereplacementtherapyshouldberaepithelialneoplasia(dVIN)IHCwhichmayshowsaberrantp53staining..."?PathologicassessmentforsquamouscellcarcinomapNewbulletadded:RecommendancillarytestingtodetermineHPVstatuseitherbyp16IHCorRNAinsituhybridizationorDNAVULVA-ESystemicTherapy?Footnotecregardingpembrolizumabwasrevised:"...metastatictumormutationalburden-high(TMB-H)[≥10mutations/megabase(mut/Mb)]tumors,asdeterminedbyanavalidatedand/orFDA-approvedtest..."?Footnotedregardingpembrolizumabwasrevised:"...orafterchemotherapyinpatientswhosetumorsexpressPD-L1(CPS≥1)asdeterminedbyanavalidatedand/orFDAapprovedtest."UPDATESVersion2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.ForelderlypatientswithvulvaroseetheNCCNGuidelinesrAdultOncologyvulvarmelanomaorMucosalvulvovaginalmelanomaPrintedbyMinTangon8/28/202211:53:31AM.Forpersonaluseonly.ForelderlypatientswithvulvaroseetheNCCNGuidelinesrAdultOncologyvulvarmelanomaorMucosalvulvovaginalmelanomaancerdexWORKUPCLINICALSTAGEaPRIMARYTREATMENTWORKUPTsmallerTe(VULVA-2)EarlystageTsmallerTe(VULVA-2)HPrTTebylsparinggeryuscell?Biopsy,uscell?Imagingbasneededfor?Imagingbasneededfordelineatingtenttentoftumororfortreatmentadenocarcinomas)?EUAcystoscopyorproctoscopyasindicated?SmokingcessationandcounselingMetastaticdiseasebeyondpelvisSeePrimaryMetastaticdiseasebeyondpelvisSeePrimaryTreatmentNMNMbeyondpelvisVULVACessation)?Considercervicalhumanpapillomavirus(HPV)andcytologytestingsiderHIVtestingc?Considersomaticmutationaltestingforvulvarmelanomaandmucosalvulvovaginalmelanomaasclinicallyindicated(siderHIVtestingcaSeePrinciplesofPathology(VULVA-A).Ifvulvovaginalmelanomaissuspected,seePrinciplesofBiopsyandPathology(ME-B)intheNCCNGuidelinesforMelanoma:Cutaneous.bSeePrinciplesofImaging(VULVA-B).Ifvulvovagionalmelanomaissuspected,SeePrinciplesofImaging(ME-D)intheNCCNGuidelinesforMelanoma:Cutaneous.cConsiderHIVtesting,especiallyinyoungerpatientssuspectedofhavingsquamouscellcarcinomaofthevulvaorotherHPV-relateddisease.PatientswithvulvarcancerandHIVshouldbereferredtoanHIVspecialistandshouldbetreatedforvulvarcanceraspertheseguidelines.ModificationstocancertreatmentshouldnotbemadesolelyonthebasisofHIVstatus.dHistologichigh-gradesquamousintraepitheliallesion(HSIL;formerlydefinedascarcinomainsitu[CIS]andincorporatesvulvarintraepithelialneoplasia2and3[VIN2/3])canbetreatedwithwidelocalexcision.eSmallerT2tumors:≤4cm.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.VULVA-1SentinellymphnodeAssessmentof(≤1mminvasion)vulvectomyf,gTsmallerT2e)primarytumoriandnodalsurgicalpathologypydonryrsodalation?SLNBhorbilateralSentinellymphnodeAssessmentof(≤1mminvasion)vulvectomyf,gTsmallerT2e)primarytumoriandnodalsurgicalpathologypydonryrsodalation?SLNBhorbilateralbiopsy(SLNB)horancerdexCLINICALSTAGEPATHOLOGICFINDINGSPRIMARYTREATMENTT1aSimplepartial T1aSimplepartial ?Ifpositivemargins,(SeeVULVA-3)2cmfromvulvarmidlineRadicalpartialvulvectomyandipsilateralaluationfinguinofemoralaluationfipsilateralinguinofemorallymphadenectomy(>1mminvasion)orT2ntralrorRadicalpartialvulvectomyandbilateralaluationfinguinofemoralaluationfeSmallerT2tumors:≤4cm.fSeePrinciplesofSurgery(VULVA-C).gIfpartialsuperficialvulvectomypathologyrevealstumorinaggregateof≥1mminvasion,thenadditionalsurgerymaybewarranted.hInguinofemorallymphadenectomyisrequiredonside(s)wheresentinelnodesarenotdetected.iSeePrinciplesofSurgery:TumorMarginStatus(VULVA-C1of5).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.VULVA-2Version2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.skfactorslPrintedbyMinTangon8/28/202211:53:31AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.skfactorslancerdexPRIMARYTUMORRISKFACTORSADJUVANTTHERAPYTOTHEPRIMARYSITEorinvasivediseasejorinvasivediseasejfNegativemarginsforinvasivediseasePositivemarginsforinvasivediseaseUnresectablewithoutexenterativeapproachorAdjuvantexternal(EBRT)kbased(EBRT)kbasedonAdjuvantEBRTkfSeePrinciplesofSurgery(VULVA-C).jThemanagementofpositivemarginsforHSIL(noninvasivedisease)shouldbeindividualized.kSeePrinciplesofRadiationTherapy(VULVA-D).lOtherprimaryriskfactorsinclude:closetumormargins,lymphovascularinvasion(LVSI),tumorsize,depthofinvasion,andpatternofinvasion(sprayordiffuse).Nodalinvolvement(asanindicatoroflymphovascularspaceinvasion)mayalsoimpactselectionofadjuvanttherapytotheprimarysite.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.VULVA-3PrintedbyMinTangon8/28/202211:53:31AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ancerdexNODALEVALUATIONADJUVANTTHERAPYTOTHENODESnodesornodes≤2mmmetastasisoconcurrentchemotherapypSinglepositive≤2mmmetastasisoconcurrentchemotherapypSLNspositivemnPositiveSLN>2mmmetastasisoCompletepypRTkpypwithpositiveLN(s)EBRTk(category1forradiationif≥2LNscurrentchemotherapyppositivecurrentchemotherapypEBRTk(category1forradiationif≥2LNscurrentchemotherapyppositivecurrentchemotherapypkSeePrinciplesofRadiationTherapy(VULVA-D).mIfipsilateralgroinispositive,thecontralateralgroinshouldbeevaluatedsurgicallyand/ortreatedwithEBRT.Inselectcasesofasingle,small-volume,unilateral,positiveinguinalnodewithawell-lateralizedprimarytumordiameter≤2cmanddepthofinvasion≤5mmandwithaclinicallynegativecontralateralgroinexamination,acontralateralinguinofemorallymphadenectomyorradiationmaybeomitted.(GonzalezBosquetJ,etal.GynecolOncol2007;105:742-746.)nSeePrinciplesofSurgery:InguinofemoralSentinelLymphNodeBiopsy(VULVA-C4of5).oThesizeof2mmisusedtoinformtreatmentselection/managementandthe5-mmcutoffisusedforstaging.SeePrinciplesofPathology(VULVA-A).pSeeSystemicTherapy(VULVA-E).SeeSurveillance(VULVA-8)Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.VULVA-4ADDITIONALTREATMENT PrintedbyMinTangon8/28/202211:53:31AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsADDITIONALTREATMENT ancerdexCLINICALSTAGEPRIMARYTREATMENT(LargerT2,q(LargerT2,qT3:Unresectablebynon-visceral–sparingprimarysurgery)?RadiologicimagingworkupifnotpreviouslydonergePositiveLNss lymphadenectomyfNegativeLNsineineneedlespirationFNAforenlargedLNes(includespelvic-confinedM1,LNRadiologicimagingtoassessextentofdiseaseedLNsConsiderFNAedLNsfSeePrinciplesofSurgery(VULVA-C).kSeePrinciplesofRadiationTherapy(VULVA-D).pSeeSystemicTherapy(VULVA-E).qLargerT2tumors:>4cmand/orinvolvementoftheurethra,vagina,oranus.rSeePrinciplesofImaging(VULVA-B).sSeePrinciplesofPathology(VULVA-A).RTkconcurrentRTkconcurrenttumor/inguinofemoralLNs/pelvicnodesRTkconcurrentRTkconcurrentumoreinguinofemoraleinguinofemoralRTkconcurrenttumoringuinofemoralLNs/Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.VULVA-5Version2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/28/202211:53:31AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ancerdexEVALUATIONOFRESPONSETOEBRT+CONCURRENTCHEMOTHERAPYADDITIONALTREATMENTBiopsyrbiopsymorbedtorbiopsymorbedtoancemoratprimarysiteandnodesCRCRtrrrSystemictherapyporvecarevecareresidualtumoratprimarysiteand/ornodesrnalEBRTknalEBRTkrctherapypvecarefSeePrinciplesofSurgery(VULVA-CvecarekSeePrinciplesofRadiationTherapy(VULVA-D).pSeeSystemicTherapy(VULVA-E).tNosoonerthan3monthsfromcompletionoftreatment.uConsiderpelvicexenterationforselectcaseswithacentralrecurrence.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.VULVA-6Version2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/28/202211:53:31AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.ancerdexCLINICALSTAGEPRIMARYTREATMENTseslvisEBRTk,vforlocoregionalcontrol/symptompalliationctherapyctherapyporBestsupportivecare(SeeNCCNGuidelinesforPalliativeCare)kSeePrinciplesofRadiationTherapy(VULVA-D).pSeeSystemicTherapy(VULVA-E).vCanconsiderablativetherapyfor1–5metastaticlesionsiftheprimaryhasbeencontrolled.(PalmaDA,etal.Lancet2019;393:2051-2058.)Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.VULVA-7Version2.2022,08/17/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon8/28/202211:53:31AM.Forpersonal