皮膚黑色素瘤2022.v2（英文）-NCCN腫瘤臨床實(shí)踐指南

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)Melanoma:CutaneousersionJanuaryNCCNGuidelinesforPatients?availableat/patientsVersion2.2022,01/26/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:38:09AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dex*SusanM.Swetter,MD/Chair?StanfordCancerInstitute*JohnA.Thompson,MD??/Vice-ChairFredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceMarkR.Albertini,MD?UniversityofWisconsineCancerCenterChristopherA.Barker,MD§MemorialSloanKetteringCancerCenterJoelBaumgartner,MD?UCSanDiegoMooresCancerCenterGenevieveBoland,MD,PhD?MassachusettsGeneralHospitalCancerCenterBartoszChmielowski,MD,PhD??UCLAJonssonComprehensiveCancerCenterDominickDiMaio,MD≠Fred&PamelaBuffettCancerCenterAlisonB.Durham,MD?UniversityofMichiganRogelCancerCenterRyanC.Fields,MD?SitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineMartinD.Fleming,MD?TheUniversityofTennesseeeCenterAnjelaGalan,MD≠YaleCancerCenter/SmilowCancerHospitalesPanelDisclosuresBrianGastman,MD?CaseComprehensiveBrianGastman,MD?CaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussignstitutethaGuildAIMatMelanomaAshleyHolder,MD?O'NealComprehensiveCancerCenteratUABJohnHyngstrom,MD?HuntsmanCancerInstituteattheUniversityofUtahlasJohnsonMDUniversityofColoradoCancerCenterAnthonyJ.Olszanski,MD,RPh?FoxChaseCancerCenterPatrickA.Ott,MD,PhD??TDana-Farber/BrighamandWomen'senterMerrickI.Ross,MD?TheUniversityofTexasAprilK.Salama,MD?DukeCancerInstituteRohitSharma,MD?ngramCancerCenterRichardW.JosephngramCancerCenterRichardW.Joseph,MD??MayoClinicCancerCentersKarakousisMDJosephSkitzki,MD?RoswellParkCancerInstituteAbramsonCancerCenterattheAbramsonCancerCenteratthensylvaniaKariKendra,MD,PhD?TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandeResearchInstituteMaijaKiuru,MD,PhD?UCDavisComprehensiveCancerCenterJulieR.Lange,MD,ScM?TheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsRobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityKatyTsai,MD?UCSFHelenDillerFamilyComprehensiveCancerCenterYanXing,MD,PhDCityofHopeNationalMedicalCenterEvanWuthrick,MD§MoffittCancerCentercMillianMSenPhD?Dermatology?Hematology/HematologyoncologyTInternalmedicine?Medicaloncology≠Pathology￥Patientadvocacy§Radiotherapy/Radiationoncology?Surgery/Surgicaloncology*WritingcommitteememberVersion2.2022,01/26/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.anelMembersaryoftheGuidelinesUpdatesClinicalPresentationandPreliminaryWorkup(ME-1)Stage0(insitu),StageIA,IB(ME-2)StageIB,anelMembersaryoftheGuidelinesUpdatesClinicalPresentationandPreliminaryWorkup(ME-1)Stage0(insitu),StageIA,IB(ME-2)StageIB,StageII(ME-3)StageIIIBMicroscopicSatellites(ME-4)StageIII(SentinelNodePositive)(ME-5)StageIII(ClinicallyPositiveNode[s])(ME-6)StageIII(ClinicalSatellite/In-Transit)(ME-7)StageIVMetastatic(ME-8)Follow-up(ME-9andME-10)CommonFollow-upRecommendationsforAllPatients(ME-11)TrueScarRecurrence(PersistentDisease)(ME-12)LocalSatellite/In-TransitRecurrence(ME-13)NodalRecurrence(ME-14)DistantMetastaticDisease(ME-16)RiskFactorsforDevelopmentofSingleorMultiplePrimaryMelanomas(ME-A)PrinciplesofBiopsyandPathology(ME-B)PrinciplesofMolecularTesting(ME-C)PrinciplesofImaging(ME-D)PrinciplesofSurgicalMarginsforWideExcisionofPrimaryMelanoma(ME-E)PrinciplesofSentinelLymphNodeBiopsy(SLNB)(ME-F)PrinciplesofCompletion/TherapeuticLymphNodeDissection(ME-G)PrinciplesofRadiationTherapyforMelanoma(ME-H)SystemicTherapyforMetastaticorUnresectableDisease(ME-I)SystemicTherapyConsiderations(ME-J)ManagementofToxicitiesAssociatedwithTargetedTherapy(ME-K)PrinciplesofBrainMetastasesManagement(ME-L)dexlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceanddationsotherwisedNCategoriesofEvidenceandConsensus.NCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2022.Version2.2022,01/26/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:38:09AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexsionoftheNCCNGuidelinesforCutaneousMelanomafromVersioninclude?StageIB(T2a)orII(T2borhigher);Adjuvanttreatment:PembrolizumabforpathologicallyStagedIIBorIICwasaddedasanoption.ThefollowingcorrespondingfootnoteswerealsoaddedonME-3A:pFootnotez:Pathologicstaging(withSLNB)forstageIIBandIICmelanomaisstronglypreferredpriortotherecommendationofadjuvantpembrolizumab-toenhancerisk/benefitpatientdiscussionsandoptimizelocal/regionaldiseasecontrol.pFootnoteaa:AdjuvantpembrolizumabisactiveinreducingrelapseeventsforresectedStageIIBandIICmelanoma.However,longerfollowupisneededtoevaluatetheimpactofadjuvantpembrolizumabonoverallsurvival.CliniciansconsideringadjuvantpembrolizumabtherapyforStagesIIBorIICdiseaseshouldhaveadetaileddiscussionwiththepatient,toweightheprosandconsoftreatmentbenefitvstoxicity.Factorstobeconsidered,inadditiontostage,includepatient’sage,performancestatus,personal/familyhistoryofautoimmunedisease,andtoleranceforrisk.FootnoteuuThefollowingreferenceregardingneoadjuvanttalimogenelaherparepvecwasadded,DummerRDE,etal.Naturemedicine9-1796.(AlsoforME-14AandME-15A)ME-CPrinciplesofMolecularTestingME-C2of8?EmergingMolecularTechnologiesforCutaneousMelanomaDiagnosisandPrognosticationpKIT(proto-oncogenec-KIT)mutations;?Thirddiamondsub-bulletrevised:"...anddifferintheirsensitivitytoKITinhibitorstherapy(eg,imatinib,sunitinib,nilotinib)."andcorrespondingreferencewasadded,GuoJ,CarvajalRD,DummerR,etal.EfficacyandsafetyofnilotinibinpatientswithKIT-mutatedmetastaticorinoperablemelanoma:finalresultsfromtheglobal,single-arm,phaseIITEAMtrial.AnnOncol2017;28:1380-1387.?Firstdashedsub-bulletrevised:"...andexon13mutations(eg,W557R,V559D,L576P,K642E)appear..."ME-DPrinciplesofImagingME-D1of5?Footnoteaisnew:Nodalultrasoundassessmentformelanomarequiresspecificradiologicexpertise.Criteriaconcerningforearlymelanomanodalinvolvementincludethefollowing:hypoechoicisland(s)inthecortex,asymmetricalfocalcorticalthickening,andperipheralvascularity,particularlywhenthereisdetectableperfusiontotheareaofcorticalthickening.CorebiopsyorFNAofsuspiciouslymphnodesshouldbedirectedtotheatypicalarea(s)withinthecortexidentifiedonultrasound.ME-D5of5?Thereferenceswereupdatetocorrespondwithfootnotea.Version2.2022,01/26/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESPrintedbyMinTangon3/14/20227:38:09AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexUpdatestoVersion1.2022oftheNCCNGuidelinesforCutaneousMelanomafromVersion2.2021include:?Pathologyreport:Neurotropism/perineuralinvasionwasadded.?Footnotedisnew:Repeatnarrow-marginexcisionalbiopsyisrecommendedifaninitialpartialbiopsyisinadequatefordiagnosisormicrostagingbutshouldnotbeperformediftheinitialspecimenmeetscriteriaforsentinellymphnodebiopsy(SLNB)staging.?Footnoteerevised:"...Moreover,sincethereisalowprobabilityofmetastasisinstageI(T1)melanomaandahigherproportionoffalse-positiveresults,GEPtestingshouldnotguideclinicaldecision-makinginthissubgroup.Onanindividualbasis,thelikelihoodofapositiveSLNBmaybeinformedbytheuseofoptimizedmultivariablenomograms/riskcalculatorsandongoinginvestigationofGEPtests..."(AlsoforME-2A,ME-3)?Footnoteiisnew:Forhistologicallypositivemarginsonthebiopsyorwideexcisionspecimen,describewhetherinsituorinvasivemelanomaispresentattheperipheraland/ordeepmargins.Forhistologicallynegativemarginsonthewideexcisionspecimen,InternationalCollaborationonCancerReporting(ICCR)andCollegeofAmericanPathologists(CAP)guidelinesdonotrequirereportingofthemicroscopicallymeasureddistancesbetweentumorandlabeledlateralordeepmargins.Thismeasurementshouldnotgenerallyimpactclinicaldecision-making.?Footnotenisnew:Pathologyreportingofextensiveversusfocalneurotropism(ie,involvingonlyasinglenervevs.multiplenervesand/orsizeofinvolvednerves)mayhelpguideclinicaldecision-making.(AlsoforME-B)FootnoteqrevisedNodalbasinultrasound(US)isnotasubstituteforSLNB.ConsidernodalbasinUSpriortoSLNBformelanomapatientswithanequivocalregionallymphnodephysicalexam.AbnormalorsuspiciousfindingsonnodalbasinUSshouldbemedhistologicallywheneverpossibleNodalbasinUSisnotasubstituteforSLNB.NegativenodalbasinUSisnotasubstituteforbiopsyofclinicallysuspiciouslymphnodes.(AlsoforME-3,ME-4A)StageIBTaorIITborhigherAdjuvanttreatment:mendationsrevisedClinicaltrialforStageIIorObservationorLocoregionalradiationtherapy(category2B).?Footnoteyrevised:"...patientpreference,orotherfactors(suchasadvancedpatientageand/orpoorfunctionalstatus)..."(AlsoforME-4A)?Footnotezisnew:ConsiderRTtositeofresectedprimarytumorinselectedhigh-riskpatientsbasedondesmoplastichistologyand/orneurotropism.SeePrinciplesofRadiationME-H.?StageIIIA(sentinelnodepositive)andStageIIIB/C/D(sentinelnodepositive)pPrimaryTreatment:Nodalbasinultrasound(US)surveillance(generallypreferred)pAdjuvantTreatment:Systemictherapybasedonriskofrecurrence?Footnoteggisnew:NodalbasinUSsurveillancemaynotbepreferredoverCLNDinallcases(eg,patientpreferenceduetothelogisticsofsurveillance,whenprimarytumorhistologyandSLNtumorburdensuggestahigherlikelihoodofadditionalregioninvolvement,and/orwhenadjuvanttherapyisnotpursued).?Footnoteffrevised:"...numberofpositivenodes,andthickness/ulcerationoftheprimarytumor.NodalbasinUSsurveillancemaynotbepreferredoverCLNDinallcases(eg,patientpreferenceduetothelogisticsofsurveillance,orwhenprimarytumorhistologyandSLNtumorburdensuggestahigherlikelihoodofadditionalregionalnodalinvolvement)."?Footnotehhrevised:"...(MSLT-IIandDeCOG;ie,every4monthsduringthefirst2years,thenevery6monthsduringyears3through5).SeePrinciplesofImaging(ME-D)."?Footnoteiiisnew:Alternativeimagingmodalities(eg,CT,MRI)maybeusedforheadandneckmelanoma.Version2.2022,01/26/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESPrintedbyMinTangon3/14/20227:38:09AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexneoadjuvanttherapymightimpactthechoiceofFootnotellrevisedNivolumabhasshownFootnotellrevisedNivolumabhasshownaclinicallysignificantvementinRFScomparedtohighdoseipilimumabbutvementinRFScomparedtohighdoseipilimumabbutitsimpactonOShasnotyetbeenreportedcomparableOSat?PatelSP,etitsimpactonOShasnotyetbeenreportedcomparableOSatmonthsoffollow-up.Pembrolizumabhasshownaclinically?BlankCU,monthsoffollow-up.PembrolizumabhasshownaclinicallysignificantimprovementinRFScomparedtoplacebo,butitssignificantimprovementinRFScomparedtoplacebo,butitsimpactonOShasnotyetbeenreported.(AlsoforonOShasnotyetbeenreported.(AlsoforME-6A,ME-14A)FootnoteqqrevisedIntheeventofFootnoteqqrevisedIntheeventofunacceptabletoxicitiestoabrafenibtrametinibOtherBRAFMEKinhibitorcombinationscanabrafenibtrametinibOtherBRAFMEKinhibitorcombinationscanbeconsideredintheeventofunacceptabletoxicitiestodabrafenib/trametiniborbasedonsideeffectprofiles.pFootnotett:ProspectivetrialssupportingthesystemictherapyoptionsonME-Iasneoadjuvanttherapyareongoing.PatientsAlsoforMEAMEA,ME-13A,ME-14A,ME-15A)shouldAlsoforMEAMEA,ME-13A,ME-14A,ME-15A)therapymaybeinfluencedbypriorsystemictherapy,includingStageIIIclinicallypositivenode[s])whenandwhatStageIIIclinicallypositivenode[s])pFootnoteuu:TumorsthatwerelocallyadvancedandunresectablepWorkup;Firstbullet:"...CorebiopsypreferredorpWorkup;Firstbullet:"...CorebiopsypreferredorFNAiffeasible.Ifneedlebiopsy..."pAfterWorkup,anewbifurcationwasaddedfor"Resectablenodaldisease"and"Unresectable/borderlineresectable".pPrimaryTreatment:Considerneoadjuvanttherapy,preferablyinthecontextofaclinicaltrialaddedasanoption.resection.Forpatientswithunresectablenodaldisease,considertreatmentwithsystemictherapyfollowedbyresection,ortreatasstageIV.Thefollowingfootnoteswereadded(AlsoforME-14A,ME-15A)veryhighriskofrecurrenceaftercompleteresection,athighriskofperioperativemorbidityduetoextentofresectionorunderlyingcomorbidities,orifachievinggrosscompleteresectionofnodaldiseaseisuncertain,recommendmultidisciplinarytumorboardreviewtoconsiderneoadjuvantsystemictherapy,preferablyinthecontextofaclinicaltrial.Multipleearlyclinicaltrialshaveinvestigatedneoadjuvanttherapy,includingsingle/combinationcheckpointinhibitors,BRAF/MEKinhibitors,andintralesionaltherapieseitheraloneorincombinationwithcheckpointinhibitors(Seereferencesbelow).ClinicaltrialshavealsobeendesignedtostudypathologicresponseafterThefollowingfootnoteswereadded(AlsoforME-14A,ME-15A)veryhighriskofrecurrenceaftercompleteresection,athighriskofperioperativemorbidityduetoextentofresectionorunderlyingcomorbidities,orifachievinggrosscompleteresectionofnodaldiseaseisuncertain,recommendmultidisciplinarytumorboardreviewtoconsiderneoadjuvantsystemictherapy,preferablyinthecontextofaclinicaltrial.Multipleearlyclinicaltrialshaveinvestigatedneoadjuvanttherapy,includingsingle/combinationcheckpointinhibitors,BRAF/MEKinhibitors,andintralesionaltherapieseitheraloneorincombinationwithcheckpointinhibitors(Seereferencesbelow).Clinicaltrialshavealsobeendesignedtostudypathologicresponseafterneoadjuvanttreatmentanditseffectonrelapse-freesurvival.Atpresent,thereisnoconsensusregardingthedurationofneoadjuvanttherapyequentsurgeryorhowpathologicresponsetoUPDATESVersion2.2022,01/26/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:38:09AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dex?Workup;Firstbulletrevisedto"CorebiopsypreferredorFNAiffeasible.Ifneedle..."?InitialtreatmentpLimitedresectabledisease?Secondbulletrevised:IntralesionalT-VEC/intralesionaltherapy(AlsoforME-13)?Thirdbulletrevised:Systemictherapy(SeeadjuvanttreatmentME-7)(AlsoforME-13)?Adjuvanttreatment;Preferredregimens:Nivolumabchangedfromcategory2Atocategory1.?Footnoteyyrevised:Therearenoclinicaldatatosupportwidersurgicalmarginsforsatellite/in-transitmetastasis;clearhistologicmarginsshouldbeachieved.Considersentinelnodebiopsyforresectableclinicalsatellite/in-transitdiseaseifitwillchangetreatmentoptions(category2B).SeePrinciplesofSentinelLymphNodeBiopsy(SLNB)(ME-F).(AlsoforME-13A)?Footnotehhhisnew:CheckMate238isaphaseIIIrandomizedstudytoevaluateadjuvantnivolumabversusipilimumabaftercompleteresectioninpatientswithstageIIIb/corstageIVmelanoma.Thestudyincluded155patientswithin-transitmelanomaonly.NivolumabshowedaclinicallysignificantimprovementinRFScomparedtohigh-doseipilimumab.OSresultswerenotreportedforthesubjectswithin-transitdiseaseonly.PembrolizumabhasshownaclinicallysignificantimprovementinRFScomparedtoplacebo,butitsimpactonOShasnotyetbeenreported.TheNCCNPanelagreesthatitisappropriatetoextendtheindicationforadjuvantanti-PD-1therapytopatientswithclinicalormacroscopicsatellite/in-transitdiseaseandwhoareatsignificantriskofrecurrence.(AlsoforME-13A)?ThefollowingfootnoteswereremovedpProspectivetrialssupportingthesystemictherapyoptionsonME-IincludedonlyasmallsubsetofpatientswithstageIIIdisease.(AlsoforME-13A)pNivolumabhasshownaclinicallysignificantimprovementinRFScomparedtohigh-doseipilimumab,butitsimpactonOSyetbeenreportedPembrolizumabhasshownaclinicallysignificantimprovementinRFScomparedtoplacebo,butitsimpactonOShasnotyetbeenreportedAlthoughbothtrialsfocusedprimarilyonpatientswithstageIIInodaldisease,theNCCNPanelagreesthatitisappropriatetoextendtheindicationforadjuvantanti-PD-1therapytopatientswithclinicalormacroscopicsatelliteintransitdiseaseandwhoareatsignificantriskofrecurrence(Note:thisfootnotewasreplacedbyfootnotehhh)(AlsoforME-13A)?Footnotelllrevised:Truescarrecurrence(persistentdisease)attheprimarytumorwideexcisionsiteisdefinedbythepresenceofinsituand/orradialgrowthphaseabuttingthesurgicalscar.(AlsoforME-10,ME-12)?Footnotemmmrevised:Localsatellite/in-transitrecurrencewithoutmetastasislacksinsituorradialgrowthphase,withandisdefinedbyintralymphaticdeepdermalorsubcutaneousfatrecurrencewithinthemelanomascarorsatellitemetastasisadjacenttothemelanomascar.Satelliteandin-transitmetastasesarebiologicallyandprognosticallysimilar.(AlsoforME-10,ME-13A)ME-11CommonFollow-upRecommendationsforAllpatients?Firstbulletrevised:H&P(withemphasisonnodesandskin)atleastannually,dependingonstage.pFirstarrowsub-bulletrevised:"Available,noninvasivepre-biopsyimagingandmoleculartechnologieshavenotbeenprospectivelycomparedfordiagnosticaccuracy.Pre-diagnosticclinicalmodalities..."pSecondarrowsub-bulletrevised:Pre-diagnosticnoninvasivegenomicpatchtestingbemayalsobehelpfultoguidebiopsydecisions.?Fifthbulletrevised:"RegionallymphnodeUSinpatientswithapositiveSLNBwhodidnotundergoCLNDshouldbeconsideredisgenerallypreferredwhereexpertiseisavailable"Version2.2022,01/26/22?2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESclinicaltrialaddedasanoption.performcomplete/therapeuticlymphnodedissection,TLNDlclinicaltrialaddedasanoption.performcomplete/therapeuticlymphnodedissection,TLNDltrialaddedasanoptionrequiresfurtherinvestigation.dexofrecurrenceSecondbulletrevisedConsiderlymphaticppingofrecurrenceSecondbulletrevisedConsiderlymphaticppingSLNBaccordingtohistopathologyofthescarrecurrenceisticspreviouslymphnodedissectionMelanomas?FifthbulletGeneticpredisposition:Newarrowsub-bulletadded,AlsoseeNCCNGuidelinesforGenetic/FamilialHigh-RiskAssessment:ColorectalandNCCNGuidelinesforGenetic/FamilialHigh-RiskAssessment:Breast,Ovarian,andPancreatic?Referencesupdated.anewbifurcationwasaddedfor"Resectable"and"Unresectable."anewbifurcationwasaddedfor"Resectable"and"Unresectable."on?Lastbulletrevised:"...initialspecimenmeetscriteriaforSLNBstaging."Firstcolumn:Firstcolumn:Under"Diseaselimitedtonodalrecurrence"anewrecommendationwasadded,Biopsytoconfirm.?recommendationwasadded,Biopsytoconfirm.RecurrenceResectableRecurrenceResectablepathway?Specificmutations(BRAF,NRAS,KIT)andimplications:Firstendashsub-bulletrevised,"...beusedinpatientswithoutactivatingmutationsinBRAFV600mutationsAdjuvantTreatmentClinicaltrial,AdjuvantTreatmentClinicaltrial,ifapplicableaddedasanoption.?Footnoteiiiwasaddedtothispage.Itisnotanewfootnote.metastaticdisease?Thirdbullet,MethodsofmutationtestingpFirstarrowsub-bullet;Firstarrowdiamondsub-bulletrevised:"...ConfirmatoryBRAFmoleculartestingisencouraged,particularlyinthesettingofanegativeIHCresult."?Workup;Lastbulletrevised:BRAFmutationtestingif?Workup;Lastbulletrevised:BRAFmutationtestingifnotpreviouslyperformedonametastaticlesion?ThirdcolumnrevisedpLimited(Resectable)Oligometastatic?Moleculartestingontumort