皮肤鳞癌2022.v1（英文）-NCCN肿瘤临床实践指南

NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines®)SquamousCellSkinCancerersionNovemberNCCNGuidelinesforPatients®availableat/patientsVersion1.2022,11/17/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:41:35AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.mousCellSkinCancerdexChrysalyneD.Schmults,MD,MS/Chairϖ¶Dana-Farber/BrighamandWomen’senterRachelBlitzblau,MD,PhD/ViceChair§DukeCancerInstituteSumairaZ.Aasi,MDϖStanfordCancerInstituteMuradAlam,MD,MBA,MSCIϖ¶ζRobertH.LurieComprehensiveCancerCenterofNorthwesternUniversityJamesS.Andersen,MD¶ŸCityofHopeNationalMedicalCenterBrianC.Baumann,MD§SitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineJeremyBordeaux,MD,MPHϖCaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussignstitutePei-LingChen,MD,PhD≠MoffittCancerCenterRobertChin,MD,PhD§UCLAJonssonComprehensiveCancerCenterCarloM.Contreras,MD¶TheOhioStateUniversityComprehensiveCancerCenter-JamesCancerHospitalandSoloveResearchInstituteDominickDiMaio,MD≠Fred&PamelaBuffettCancerCenternesPanelDisclosuresJessicaM.Donigan,MDϖHuntsmanCancerInstituteattheUniversityofUtahJeffreyM.Farma,MD¶FoxChaseCancerCenterMaxwellA.Fung,MDϖ≠UCDavisComprehensiveCancerCenterKarthikGhosh,MDÞCancerCenterRoyC.Grekin,MDϖ¶UCSFHelenDillerFamilyComprehensiveCancerCenterKellyHarms,MD,PhDϖUniversityofMichiganRogelCancerCenterAlanL.Ho,MD,PhD†MemorialSloanKetteringCancerCenterAshleyHolder,MD¶O’NealComprehensiveCancerCenteratUABJohnNicholasLukens,MD§AbramsonCancerCenterattheUniversityofPennsylvaniaTheresaMedina,MD†UniversityofColoradoCancerCenterKishwerS.Nehal,MDϖ¶MemorialSloanKetteringCancerCenterPaulNghiem,MD,PhDϖFredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceSooPark,MD†UCSanDiegoMooresCancerCenterTejeshPatel,MDϖ≠St.JudeChildren’sResearchHospital/UniversityofTennesseeHealthScienceIgorPuzanov,MD,MSCI†RoswellParkComprehensiveCancerCenterJeffreyScott,MD,MHSϖTheSidneyKimmelComprehensiveCancerCenteratJohnHopkinsAleksandarSekulic,MD,PhDϖMayoClinicCancerCenterAshokR.Shaha,MD¶ζMemorialSloanKetteringCancerCenterDivyaSrivastava,MDϖUTSouthwesternSimmonsComprehensiveCancerCenterWilliamStebbins,MDϖ¶Vanderbilt-IngramCancerCenterValenciaThomas,MDϖTheUniversityofTexasYaohuiG.Xu,MD,PhDϖUniversityofWisconsineCancerCenterenPhDMcCulloughRNBSBDermatologyÞInternalmedicine†MedicaloncologyζOtolaryngology≠Pathology/DermatopathologyŸReconstructivesurgery§Radiotherapy/Radiationoncology¶Surgery/Surgicaloncology*DiscussionSectionWritingCommitteeVersion1.2022,11/17/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.usCellSkinCancerPanelMembersaryoftheGuidelinesUpdatesinicalPresentationWorkupDiagnosisandRiskStatusSCCTreatmentforLocalLowRiskSquamousCellusCellSkinCancerPanelMembersaryoftheGuidelinesUpdatesinicalPresentationWorkupDiagnosisandRiskStatusSCCTreatmentforLocalLowRiskSquamousCellSkinCancerSCCorLocalHighRiskVeryHighRiskSquamousCellSkinCancerSCCeoperativeAssessmentandPrimaryTreatmentSCCegionalLymphNodesSCCPathologySCCAificationtoDetermineTreatmentOptionsandFollowupforLocalCSCCBasedonRiskFactorsforLocalRecurrenceMetastasesorDeathfromDiseaseSCCB)IdentificationandManagementofPatientsatHighRiskforMultiplePrimaryCSCCs(SCC-C)mentSCCDiationTherapySCCEesofSystemicTherapySCCFmousCellSkinCancerdexlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceanddationsotherwiseindicated.ategoriesofEvidenceensusNCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualclinicalcircumstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetwork®(NCCN®)makesnorepresentationsorwarrantiesofanykindregardingtheircontent,useorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinghtsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.©2021.Version1.2022,11/17/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion1.2022,11/17/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:41:35AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.mousCellSkinCancerdexersionoftheNCCNGuidelinesforSquamousCellSkinCancerfromVersionincludeGlobalchanges:•Changed"Mohsmicrographicsurgery(MMS)orotherformsofCCPDMA"to"MohsorotherformsofPDEMA."•Changed"Completecircumferentialperipheralanddeepmarginassessment(CCPDMA)"to"Peripheralanddeepenfacemarginassessment(PDEMA)."•Changed"CCPDMA"to"PDEMA."•Changed"MMS"to"Mohs."SCC-1•WorkuppSecondsub-bulletunderH&Prevised:Regionallymphnodeexamasindicatedforsuspicionofnodaldisease.•Footnoteerevised:Forrarecasesthatpresentwithdistantmetastaticdiseaseatdiagnosis,treatasdistantmetastasespathwayonSCC-6.Imagingmodalityandtargetedareashouldbeatthediscretionofthetreatingteambasedonthesuspectedextentofdisease(ie,local,regional,metastatic).•Footnotegadded:Imagingmodalityandtargetedareashouldbeatthediscretionofthetreatingteambasedonthesuspectedextentofdisease(ie,local,regional,metastatic).Histologicconfirmationisoftensufficienttodiagnoselocalrecurrence,butMRIcanbeconsideredtoassessextentoflocaldisease.Fornodalordistantmetastases,histologicanalysisand/orotherimagingmodalitiescanbeemployedforconfirmationandtogaugeextentofdisease.SCC-2•PrimaryTreatmentpCurettageandelectrodesiccation(C&E),secondbulletrevised:Iftumorappearstobenotconfinedtoskin(penetratesbeyondtheskin)extendbeyondthedermis,surgicalexcisionshouldgenerallybeperformedratherthanC&E.pSecondoptionrevised:Standardexcisionwith4-to6-mmclinicalmarginsandpostoperativemarginassessment.Tissuerearrangement(eg,flapreconstruction,extensiveundermining)shouldnotbeundertakenuntilclearmarginsareidentifiedand(secondintentionhealing,linearrepair,orskingraftareacceptable).pOptionadded:Mohsorotherformsofperipheralanddeepenfacemarginassessment(PDEMA).SCC-2(continued)•Footnotesremoved:pClosureslikeadjacenttissuetransfers,inwhichsignificanttissuerearrangementoccurs,arebestperformedafterclearmarginsareverified.(AlsopageSCC-3A)pRTisoftenreservedforpatientsolderthan60yearsbecauseofconcernsaboutlong-termsequelae.(AlsopageSCC-3A)•Footnotejrevised:Excisionwithcompletecircumferentialperipheralanddeepmarginassessment(CCPDMA)PDEMAwith(viapermanentsectionanalysisorintraoperativefrozensectionanalysis)isanalternativetoMMSMohs.SeePrinciplesofCCPDMAPDEMATechnique(SCC-G).(AlsopageSCC-3A)•Footnotekadded:WhenMohsisbeingperformedandthepreoperativebiopsyisconsideredinsufficientforprovidingallthestaginginformationrequiredtoproperlytreatthetumor,submissionofthecentralspecimenforverticalparaffin-embeddedpermanentsectionsordocumentationofstagingparametersinMohsreportisrecommended.SCC-3•PrimaryTreatmentpSecondoptionrevised:Standardexcisionwithwidersurgicalmarginsandpostoperativemarginassessmentandsecondintentionhealing,linearrepair,ordelayedrepairskingraft.pPathwayfollowingMohsorotherformsofPDEMA,Negativemarginsrevised:Ifextensiveperineural,large,ornamednerveinvolvement,orifotherhigh-riskfeaturespoorprognosticfeatures:RecommendmultidisciplinaryconsultationandConsideradjuvantRT.UPDATESVersion1.2022,11/17/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:41:35AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.mousCellSkinCancerdexersionoftheNCCNGuidelinesforSquamousCellSkinCancerfromVersioninclude•Footnotesrevised:pFootnotek:WhenMMSMohswithmarginassessmentisbeingperformedandthepreoperativebiopsyisconsideredinsufficientforprovidingallthestaginginformationrequiredtoproperlytreatthetumor,submissionofthecentralspecimenforverticalparaffin-embeddedpermanentsectionsordocumentationofstagingparametersinMohsreportisrecommended.pFootnotel:Forcomplicatedcases,considermultidisciplinaryconsultation.ForlocallyadvanceddiseaseinwhichcurativeRTandcurativesurgeryarenotfeasible,considertreatmentwithimmunotherapysystemictherapyi-mab-rwlcorclinicaltrial).SeePrinciplesofSystemicTherapypFootnoteo:Discussandconsidersentinellymphnodebiopsy(SLNB)priortoPDEMAforpatientswiththevery-high-riskCSCCsthatarerecurrentorhavemultipleriskfactorsplacingtheminvery-high-riskgroup,andhavenormalexamofdrainingnodalbasin(category2B).SeeStratificationtoDetermineTreatmentOptionsandFollow-upforLocalCSCCBasedonRiskFactorsforLocalRecurrence,Metastases,orDeathfromDisease(SCC-B).pFootnotep:Ifinvasiontoparotidfascia,superficialparotidectomyismaybeindicated.pFootnotes:LargenerveinvolvementisdefinedbytheAmericanJointCommitteeonCancer(AJCC)CancerStagingManual,8thEditionforCSCCoftheheadandneckas≥0.1mmornerveinvolvementdeeperthanthedermis.;mMostnervesdeeptothedermisare>0.1mm.pFootnoteu:Fortumorsincheeks,forehead,scalp,neck,andpretibiathatare<6mmindepthandconfinedtothedermis...SCC-4•ClinicalStagingandPreoperativeAssessmentpOptionfollowingFNAorcorebiopsy,Negativerevised:Considerre-evaluation:clinicalexam,CTwithcontrastofthenodalbasin,repeatFNA,corebiopsy,oropenlymphnodeexcisionalbiopsy.•PrimaryTreatmentpOptionfollowingSurgicalevaluationrevised:Unresectable,inoperable,ornotfullyincompletelyresectableresecteddisease.•Footnotexadded:AnopenbiopsymaybeconsideredtoconfirmanegativeinitialFNAorcorelymphnodebiopsyifclinicalsuspicionremainshigh.•Footnotesrevised:pFootnotegrevised:Imagingmodalityandtargetedareashouldbeatthediscretionofthetreatingteambasedonthesuspectedextentofdisease(ie,local,regional,metastatic).Histologicconfirmationisoftensufficienttodiagnoselocalrecurrence,butMRIcanbeconsideredtoassessextentoflocaldisease.Fornodalordistantmetastases,histologicanalysisand/orCTotherimagingmodalitiescanbeemployedforconfirmationandtogaugeextentofdisease.pFootnoteffrevised:SurveillanceCTwithcontrastimagingofregionalnodalbasinandtoevaluatefordistantmetastaticdisease,ideallybasedonmultidisciplinaryboardrecommendation,orasclinicallyindicated.•Footnoteggadded:Underhighlyselectivecircumstances,inthecontextofmultidisciplinaryconsultation,resectionoflimitedmetastasescanbeconsidered.SCC-A•Secondheaderrevised:PrinciplesofExcisionReporting(includingMohsmicrographicexcisions)pThirdbulletrevised:Immunohistochemistrymaybeutilizedasneededtohelpidentifylymphovascularornerveinvasion,ortoidentifysingletumorcellsorsmallaggregatesfew-celltumorfoci.•Thirdheaderrevised:RecommendedElementsforPathologyReportingofExcisionalSpecimens(includingMohsmicrographicexcisions).SCC-B2of2•Footnote1revised:Riskstratificationcategoryassignmentshouldbebasedonthehighestriskfactorpresent.Thehigh-riskgrouphaselevatedriskoflocalrecurrence;thevery-high-riskgrouphaselevatedriskoflocalrecurrenceandelevatedriskofmetastasis.UPDATESVersion1.2022,11/17/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:41:35AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.mousCellSkinCancerdexersionoftheNCCNGuidelinesforSquamousCellSkinCancerfromVersionincludeSCC-C2of3•Firstheaderrevised:TreatmentofPrecancers(DiffuseActinicKeratoses,FieldCancerization,andCSCCProphylaxis).pBulletadded:UseofnicotinamidemaybeeffectiveinreducingthedevelopmentofCSCCs.pSecondbullet,firstsub-bulletrevised:Acceptedtreatmentmodalitiesincludecryotherapy,topical5-fluorouracil(5-FU)(preferred)withorwithoutcalcipotriol(calcipotriene),topicalimiquimod,topicalingenolmebutatetopicaltirbanibulin,photodynamictherapy(eg,aminolevulinicacid[ALA],porfimersodium),andC&E...•TreatmentofSkinCancerspSecondbulletrevised:Inpatientswhodevelopmultipleadjacenttumorsincloseproximity,surgicalexcisionofinvasivediseasesometimesdoesnotincludesurroundinginsitudisease,andtissuerearrangementshouldbeminimized.Insitudiseasemaythenbetreatedwithtopicalapproachessimilartoactinickeratoses/fieldcancerization.secondaryapproaches.•Footnote2added:ThelongestdurationofprophylaxisagainstSCChasbeendemonstratedwith5-FUpluscalcipotriol.•Referencesupdated.SCC-C3of3•Referencesupdated.SCC-D•Bulletremoved:UseofnicotinamidemaybeeffectiveinreducingthedevelopmentofCSCCs.SCC-E•Bulletadded:Isotope-basedbrachytherapycanbeaneffectivetreatmentforcertainsitesofdisease,particularlyontheheadandneck.•Lastbulletrevised:Thereareinsufficientlong-termefficacyandsafetydatatosupporttheroutineuseofradioisotopeorelectronicsurfacebrachytherapy.SCC-F1of2•Secondheaderrevised:PrimaryandRecurrentLocallyAdvancedDiseaseinNon-SurgicalCandidates(SeeSCC-3)•NewRegionalDiseasepThirdbulletrevised:Forpatientswithunresectable,inoperable,ornotfullyincompletelyresectableresecteddiseaseinoperableorincompletelyresectedregionaldisease,multidisciplinaryconsultationtoconsider.•Table1:SystemicTherapyOptionsforUsewithRTpUsefulinCertainCircumstances,optionrevised:Carboplatin±paclitaxelSCC-F2of2•Reference3revised:RecentpublishedphaseIItrialdatareportedanobjectiveresponse(OPR)of44%(95%CI,32-55),partialresponserate(PR)of31%andcompleteresponserate(CR)of13%tocemiplimab-rwlcinpatientswithlocallyadvancedorrecurrentCSCC.DatafromthephaseIIKEYNOTE-629trial,whichincludedpatientswithrecurrentormetastaticCSCCorlocallyadvancedCSCC,reportedanOPRof50%(95%CI,36-64),aPRof33%,andaCRof17%,forpatientstreatedwithpembrolizumab.supporttheefficacyandsafetyofcemiplimab-rwlcandpembrolizumabinpatientswithlocallyadvanced,recurrent,andmetastaticCSCC.PreliminarydataandtheclinicalexperienceofNCCNPanelMemberssuggestthatotheranti–PD-1inhibitorsmayalsobeeffectiveinthissetting.•Referencesupdated.SCC-G•Headerrevised:PrinciplesofCCPDMAPDEMATechnique•Newbulletadded:ThemostcommonlyusedformofPDEMAisMohs.Whenanatomicstructuresatthedeepmargin(eg,majorvessels,nerves,bone)precludecompletehistologicevaluationofthemarginalsurfaceviaMohsorotherformsofPDEMA,MohsorotherformsofPDEMAshouldbeusedtoevaluateasmuchofthemarginalsurfaceasfeasible.Treatmentconsiderationsfornon-visualizedareasmaybethesubjectofmultidisciplinarydiscussion.CSCCrmedfImagingstudiesofareaofinterestPrintedbyMinTangon3/14/20227:41:35AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.CSCCrmedfImagingstudiesofareaofinterestmousCellSkinCancerdexCLINICALPRESENTATIONsuspiciousforWORKUPWORKUPHPpCompleteskinexampRegionallymphnodeexamasindicatedforsuspicionofnodalamousamouscell•Biopsy:bpIfmorethansuperficiallesion,deepreticularsivediseasedegassivediseasedegRISKSTATUSLowriskcHighrisk/VeryyorradiographicallyyorradiographicallyphDistantmetastaticdiseaseryrynicalStagingandPreoperativeAssessment(SCC-4)onalenceortastasesaFormoreinformation,seeAmericanAcademyofDermatologyAssociation:/public/diseases/skin-cancer/squamous-cell-carcinoma.bSeePrinciplesofPathology(SCC-A).cSeeStratificationtoDetermineTreatmentOptionsandFollow-upforLocalCSCCBasedonRiskFactorsforLocalRecurrence,Metastases,orDeathfromDisease(SCC-B)andIdentificationandManagementofPatientsatHighRiskforMultiplePrimaryCSCCs(SCC-C).dExtensivediseaseincludesdeepstructuralinvolvementsuchasbone,perineuraldisease,anddeepsofttissue.Ifperineuraldiseaseordeepsofttissueinvolvementissuspected,MRIwithcontrastispreferred.Ifbonediseaseissuspected,CTwithcontrastispreferredunlesscontraindicated.eForrarecasesthatpresentwithdistantmetastaticdiseaseatdiagnosis,treatasdistantmetastasespathwayonSCC-6.fIncludingCSCCinsitu(showingfull-thicknessepidermalatypia,excludingactinickeratoses).gImagingmodalityandtargetedareashouldbeatthediscretionofthetreatingteambasedonthesuspectedextentofdisease(ie,local,regional,metastatic).Histologicconfirmationisoftensufficienttodiagnoselocalrecurrence,butMRIcanbeconsideredtoassessextentoflocaldisease.Fornodalordistantmetastases,histologicanalysisand/orotherimagingmodalitiescanbeemployedforconfirmationandtogaugeextentofdisease.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version1.2022,11/17/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.SCC-1PrintedbyMinTangon3/14/20227:41:35AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.mousCellSkinCancerdexPRIMARYTREATMENThCurettageandelectrodesiccation(C&E):•Excludingterminalhair-bearingareassuchasscalp,pubic,axillaryregions,andbeardareainmalesIftumorappearstoextendbeyondthedermis,surgicalexcisionshouldgenerallybeperformedratherthanC&EMohskMohskorotherformsofPDEMAjPositiveclinicallyfeasibleskPositiveclinicallyfeasiblesklowUpRTifornon-surgicalcandidateshmarginsandpostoperativemarginassessment.Tissuerearrangement(eg,flapreconstructionundermining)shouldnotbeundertakenuntilclearmarginsareidentified(secondintentionhealing,linearrepair,orskingraftareacceptable)epenfacemarginassessmentPDEMAjMohskorepenfacemarginassessmentPDEMAjRadiationtherapy(RT)ifornon-surgicalcandidateshbSeePrinciplesofPathology(SCC-A).cSeeStratificationtoDetermineTreatmentOptionsandFollow-upforLocalCSCCBasedonRiskFactorsforLocalRecurrence,Metastases,orDeathfromDisease(SCC-B)andIdentificationandManagementofPatientsatHighRiskforMultiplePrimaryCSCCs(SCC-C).hSeePrinciplesofTreatment(SCC-D).iSeePrinciplesofRadiationTherapy(SCC-E).submissionofthecentralspecimenforverticalparaffin-embeddedpermanentsectionsordocumentationofstagingparametersinMohsreportisrecommended.enanir()esubmissionofthecentralspecimenforverticalparaffin-embeddedpermanentsectionsordocumentationofstagingparametersinMohsreportisrecommended.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.SCC-2Version1.2022,11/17/21©2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.•RTi±systemictherapyrSystemictherapyifcurativeRTnotfeasiblelPDEMAjnotfeasible•RTi±systemictherapyrnot•SystemictherapyifcurativeRTsiblelPrintedbyMinTangon3/14/20227:41:35AM.Forpersonaluse•RTi±systemictherapyrSystemictherapyifcurativeRTnotfeasiblelPDEMAjnotfeasible•RTi±systemictherapyrnot•SystemictherapyifcurativeRTsiblelmousCellSkinCancerdexPRIMARYTREATMENThLocal,high-risk/hlhlmeresectiffeasibleeresectiffeasiblePositivemarginsPositiveeferredforMohseferredforveryhighrisk)j,n,o,p,uIfextensiveperineural,large,veryhighrisk)j,n,o,p,ufeatures:b,sinvolvement,orifotherfeatures:b,smultidisciplinaryconsultationandmarginsardmultidisciplinaryconsultationandmarginsardexcisionwithwidersurgicalmarginsqpostoperativemarginassessmentn,oandIfresidualpostoperativemarginassessmentn,oandecondintentionhealingecondintentionhealingPositiveFornon-surgicalcandidates:•RTi±systemictherapyr•SystemictherapyifcurativeRTnotfeasiblelHYPERLINK