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NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines®)MerkelCellCarcinomaersionMarchVersion2.2022,03/24/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/26/202210:10:19AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexChrysalyneD.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&PamelaBuffettCancerCenteresPanelDisclosuresJessicaM.Donigan,MDϖHuntsmanCancerInstituteattheUniversityofUtahJeffreyM.Farma,MD¶FoxChaseCancerCenterKarthikGhosh,MDÞCancerCenterRoyC.Grekin,MDϖ¶UCSFHelenDillerFamilyComprehensiveCancerCenterKellyHarms,MD,PhDϖUniversityofMichiganRogelCancerCenterAlanL.Ho,MD,PhD†MemorialSloanKetteringCancerCenterJohnNicholasLukens,MD§AbramsonCancerCenterattheUniversityofPennsylvaniaTheresaMedina,MD†UniversityofColoradoCancerCenterKishwerS.Nehal,MDϖ¶MemorialSloanKetteringCancerCenterPaulNghiem,MD,PhDϖFredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceKellyOlino,MD¶YaleCancerCenter/SmilowCancerHospitalSooPark,MD†UCSanDiegoMooresCancerCenterTejeshPatel,MDϖ≠St.JudeChildren’sResearchHospital/UniversityofTennesseeHealthScienceCenterIgorPuzanov,MD,MSCI†RoswellParkComprehensiveCancerCenterJeffreyScott,MD,MHSϖTheSidneyKimmelComprehensiveCancerCenteratJohnHopkinsAleksandarSekulic,MD,PhDϖMayoClinicCancerCenterAshokR.Shaha,MD¶ζMemorialSloanKetteringCancerCenterDivyaSrivastava,MDϖUTSouthwesternSimmonsComprehensiveCancerCenterValenciaThomas,MDϖTheUniversityofTexasYaohuiG.Xu,MD,PhDϖUniversityofWisconsineCancerCenterMehranYusuf,MD§O'NealComprehensiveCancerCenteratUABenPhDMcCulloughRNBSBDermatologyÞInternalmedicine†MedicaloncologyζOtolaryngology≠Pathology/DermatopathologyŸReconstructivesurgery§Radiotherapy/Radiationoncology¶Surgery/Surgicaloncology*DiscussionSectionWritingCommitteeVersion2.2022,03/24/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.ellCarcinomaPanelMembersaryoftheGuidelinesUpdateseliminaryWorkupDiagnosisAdditionalWorkupandClinicalFindingsMCC)ellCarcinomaPanelMembersaryoftheGuidelinesUpdateseliminaryWorkupDiagnosisAdditionalWorkupandClinicalFindingsMCC)tTreatmentofClinicalNDiseaseMCCtTreatmentofClinicalNDiseaseMCCtmentofClinicalMDiseaseMCCpRecurrenceandTreatmentMCCPrinciplesofPathologyMCC-A)iationTherapyMCCBExcisionMCCCsofSystemicTherapyMCCDdexlievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.ofEvidenceanddationsotherwiseindicated.ategoriesofEvidenceensusNCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNllrightsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.©2022.Version2.2022,03/24/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion2.2022,03/24/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/26/202210:10:19AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexrsionoftheNCCNGuidelinesforMerkelCellCarcinomafromVersioninclude•TheDiscussionsectionhasbeenupdatedtoreflectthechangesinthealgorithm.rsionoftheNCCNGuidelinesforMerkelCellCarcinomafromVersioninclude•Footnotecrevised:ImagingisencouragedinmostcasesofMCC.ImagingisindicatedwhenevermetastaticorunresectablediseaseissuspectedbasedonH&Pfindings...(AlsopageMCC-2A,MCC-3,MCC-5)•Footnoteeadded:AsimmunosuppressioninMCCisariskfactorforpooroutcomes,immunosuppressivetreatmentsshouldbeminimizedasclinicallyfeasibleinconsultationwiththerelevantmanagingphysician.Asimmunosuppressedpatientsareathighriskforrecurrence,morefrequentfollow-upmaybeindicated.(AlsopageMCC-4,MCC-5)MCC-2•ManagementofthePrimaryTumor:pFollowing≥1baselineriskfactor,categoryrevised:NarrowmargineExcisionwithindividualizedmarginsandmultimodaltherapydeterminedfrommultidisciplinaryassessmentincludingradiationoncology.•ManagementoftheDrainingNodalBasin:pFollowingSLNnegative,secondoptionrevised:MayconsiderRTtothenodalbasininhigh-riskpatientsatincreasedriskforafalse-negativeSLNB.MCC-2A•Footnotesrevised:pFootnoteh:Baselineriskfactors:largerprimarytumor(>21cm);chronicT-cellimmunosuppression,HIV,CLL,solidorgantransplant;head/neckprimarysite;lymphovascularinvasionpresent.pFootnotej:Intheheadandneckregion,riskoffalse-negativeSLNBsishigherduetoaberrantlymphnodedrainageandfrequentpresenceofmultipleSLNbasins.IfSLNBisnotperformedorisunsuccessful,considerirradiatingnodalbedsforsubclinicaldisease.ConsiderempiricRTtothenodalbasinwhen:1)theaccuracyofSLNBmayhavebeensubjecttoanatomiccompromise(lymphomainvolvednodes,orhistoryofremotelymphnodeexcision);2)whentheriskoffalse-negativeSLNBishighduetoaberrantlymphnodedrainageandpresenceofmultipleSLNbasins(suchasinhead&neckormidlinetrunkMCC);or3)whenidentifiedbylymphoscintigraphyincasesofprofoundimmunosuppression(ie,solidorgantransplantrecipients).SeePrinciplesofRadiationTherapy(MCC-B).pFootnotel:SLNBistypicallyperformedatthistime.pFootnoten:MohsorCCPDMAotherformsofperipheralanddeepenfacemarginassessment(PDEMA),usingmarginssimilartoWLE[widelocalexcision]widelocalexcision(WLE),maybeappropriate.SeeNCCNGuidelinesforSquamousCellSkinCancer-PrinciplesofCCPDMAPDEMATechniquefordescriptionofCCPDMAPDEMA.pFootnotes:Neoadjuvant/aAdjuvantchemotherapymaybeconsideredinselectclinicalcircumstances;however,availableretrospectivestudiesdonotsuggestsurvivalbenefitforneoadjuvant/adjuvantchemotherapy.Nodataareavailabletosupporttheadjuvantuseofimmunotherapyoutsideofaclinicaltrial.SeePrinciplesofSystemicTherapy(MCC-D).(AlsopageMCC-3)PrintedbyMinTangon3/26/202210:10:19AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexrsionoftheNCCNGuidelinesforMerkelCellCarcinomafromVersionincludeMCC-2A(continued)•Footnoteremoved:ConsiderRTwhenthereisapotentialforanatomic(eg,previoushistoryofsurgeryincludingWLE),operator,orhistologicfailure(eg,failuretoperformappropriateimmunohistochemistryonSLNs)thatmayleadtoafalse-negativeSLNB.ConsiderRTincasesofprofoundimmunosuppression.MCC-3ClinicalN:pHeaderrevised:ClinicalN+(regionalMCC).•ManagementoftheDrainingNodalBasin,Positive,followingM0:pThirdbulletrevised:Clinicaltrialforneoadjuvantoradjuvanttherapypreferredifavailable.pNewbulletadded:Considerneoadjuvantimmunotherapy.•Footnotetadded:SeePrinciplesofSystemicTherapy(MCC-D).MCC-4ClinicalM:pHeaderrevised:ClinicalM1(DisseminatedMCC).•Footnotevrevised:Underhighlyselectivecircumstances,inthecontextofmultidisciplinaryconsultation,resectionofoligometastasislimitedmetastasescanbeconsidered.(AlsopageMCC-5)MCC-5•Footnoteremoved:Asimmunosuppressedpatientsareathighriskforrecurrence,morefrequentfollow-upmaybeindicated.Immunosuppressivetreatmentsshouldbeminimizedasclinicallyfeasible,inconsultationwiththeirmanagingphysician.•Footnotewadded:Patientsathighriskofrecurrenceincludethosewhoareimmunosuppressedandpatientswhohavepositivenon-SLNmetastases.MCC-B1of2•FollowingResectionofPrimaryMCC:pRemoved:orConsiderobservation.•Footnoteremoved:Considerobservationoftheprimarysiteincaseswheretheprimarytumorissmall(eg,<1cm)andwidelyexcisedwithnootheradverseriskfactorssuchasLVIorimmunosuppression.MCC-B2of2•SLNBwithoutLNdissection,SLNnegativerevised:SLNnegative-RTnotroutinelyindicated,unlessatriskforfalse-negativeSLNB.•Footnotesremoved:pConsiderRTwhenthereisapotentialforanatomic(eg,previousWLE),operator,orhistologicfailure(eg,failuretoperformappropriateimmunohistochemistryonSLNs)thatmayleadtoafalse-negativeSLNB.pIntheheadandneckregion,riskoffalse-negativeSLNBishigherduetoaberrantlymphaticdrainageandfrequentpresenceofmultipleSLNbasins.IfSLNBisunsuccessful,considerirradiatingdrainingnodalbasinforsubclinicaldisease.pConsiderRTtodrainingnodalbasinidentifiedbylymphoscintigraphyincasesofprofoundimmunosuppression(ie,solidorgantransplantrecipients).UPDATESVersion2.2022,03/24/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/26/202210:10:19AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexrsionoftheNCCNGuidelinesforMerkelCellCarcinomafromVersionincludeMCC-B2of2(continued)•Footnote3added:ConsiderempiricRTtothenodalbasinwhen:1)theaccuracyofSLNBmayhavebeensubjecttoanatomiccompromise(lymphomainvolvednodes,orhistoryofremotelymphnodeexcision);2)whentheriskoffalse-negativeSLNBishighduetoaberrantlymphnodedrainageandpresenceofmultipleSLNbasins(suchasinhead&neckormidlinetrunkMCC);or3)whenidentifiedbylymphoscintigraphyincasesofprofoundimmunosuppression(ie,solidorgantransplantrecipients).MCC-C•SurgicalApproaches:pSecondsub-bulletrevised:IfadjuvantRTmaynotbeindicated(SeeMCC-2),performwideexcisionwith1-to2-cmmarginstoinvestingfasciaofmuscleorpericraniumwhenclinicallyfeasibleandconsistentwithreconstructionandradiationgoalslistedbelow.pThirdsub-bulletrevised:Techniquesformoreexhaustivehistologicmarginassessmentmaybeconsidered(Mohsmicrographicsurgery,CCPDMAorotherformsofPDEMA),providedtheydonotinterferewithSLNBwhenindicated.•Footnote2revised:IfWhenMohsmicrographicsurgeryisused,adebulkedspecimenofthecentralportionofthetumorshouldbesentforpermanentverticalsectionmicrostaging.beingperformedandthepreoperativebiopsyisconsideredinsufficientforprovidingallthestaginginformationrequiredtoproperlytreatthetumor,submissionofthecentralspecimenforverticalparaffin-embeddedpermanentsectionsordocumentationofstagingparametersinMohsreportisrecommended.•Footnoteremoved:CCPDMA=completecircumferentialperipheralanddeepmarginassessment.MCC-D•Headerrevised:LocalDiseaseN0pFirstbulletrevised:Forprimarydisease,adjuvantchemotherapyisnotrecommended.•Headerrevised:RegionalDiseaseN+pBulletremoved:Forrecurrentregionaldisease,considerpembrolizumabifcurativesurgeryandcurativeRTarenotfeasible.pSecondbulletrevised:Forregionaldisease,neoadjuvant/adjuvantchemotherapyisnotroutinelyrecommendedforregionaldiseaseassurvivalbenefithasnotbeendemonstratedinavailableretrospectivestudies,butcouldbeusedonacase-by-casebasisifclinicaljudgmentdictates.Nodataareavailabletosupporttheadjuvantuseofimmunotherapyoutsideofaclinicaltrial.pOptionsusefulincertaincircumstances:◊Optionadded:Neoadjuvantnivolumab.pBulletadded:Forrecurrentregionaldisease,considerpembrolizumabifcurativesurgeryandcurativeRTarenotfeasible.•Headerrevised:DisseminatedDiseaseM1pPreferredinterventions,Pembrolizumab:reference4added.•Referenceadded:TopalianSL,BhatiaS,AminA,etal.NeoadjuvantnivolumabforpatientswithresectableMerkelcellcarcinomaintheCheckMate358Trial.JClinOncol2020;38:2476-2487. SeePrimaryandAdjuvantinicalN SeePrimaryandAdjuvantlinicalNinicalMPrintedbyMinTangon3/26/202210:10:19AM.Forpersonaluseonly.Notapprovedfor SeePrimaryandAdjuvantinicalN SeePrimaryandAdjuvantlinicalNinicalMdexPRELIMINARYPRELIMINARYWORKUPPRESENTATIONforskincanceraforskincancerabeosinbeosinHEDIAGNOSISCLINICALFINDINGSCLINICALFINDINGSWORKUPHP•Completeskinandlymphnodeexamination•Imagingstudiesandlyindicatedclyindicatedcd•Multidisciplinaryconsultationrecommended•Ifpatientisimmunosuppressed,considermodificationorreductionofpriateeaFormoreinformation,seeAmericanAcademyofDermatologyAssociation:/public/diseases/skin-cancer/merkel-cell-carcinoma.bSeePrinciplesofPathology(MCC-A).cImagingisencouragedinmostcasesofMCC.ImagingisindicatedwhenevermetastaticorunresectablediseaseissuspectedbasedonH&Pfindings.Occultmetastaticdiseasethatresultedinupstaginghasbeendetectedin12%–20%ofpatientspresentingwithoutsuspiciousH&Pfindings(SinghN,etal.JAmAcadDermatol2021;84:330-339).Whole-bodyPETwithfusedaxialimaging(CTorMR)orchest/abdomen/pelvisCTwithcontrast,withneckCTifprimarytumoronhead/neckorbrainMRIifclinicalsuspicion,maybeusefultoidentifyandquantifyregionalanddistantmetastases.Severalstudiesindicatewhole-bodyPETwithfusedaxialimagingismoresensitivefordetectingoccultmetastaticdiseaseatbaseline.Imagingmayalsobeusefultoevaluateforthepossibilityofaskinmetastasisfromanoncutaneousprimaryneuroendocrinecarcinoma(eg,smallcelllungcancer),especiallyincaseswhereCK20isnegative.Themostreliablestagingtooltoidentifysubclinicalnodaldiseaseissentinellymphnodebiopsy(SLNB)(GeorgeA,etal.NuclMedCommun2014;35:282-290;HawrylukEB,etal.JAmAcadDermatol2013;68:592-599;SivaS,etal.JNuclMed2013;54:1223-1229).dQuantitationofserumMerkelcellpolyomavirus(MCPyV)oncoproteinantibodiesmaybeconsideredaspartofinitialworkup;seronegativepatientsmayhaveahigherriskofrecurrence;inseropositivepatients,arisingtitermaybeanearlyindicatorofrecurrence;baselinetestingshouldbeperformedwithin3monthsoftreatment,becausetitersareexpectedtodecreasesignificantlyafterclinicallyevidentdiseaseiseliminated.eAsimmunosuppressioninMCCisariskfactorforpooroutcomes,immunosuppressivetreatmentsshouldbeminimizedasclinicallyfeasibleinconsultationwiththerelevantmanagingphysician.Asimmunosuppressedpatientsareathighriskforrecurrence,morefrequentfollow-upmaybeindicated.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.MCC-1Version2.2022,03/24/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.selineologyilmnoNDsitiveselineimagingtperformedcHEDRAININGentinellymphnodebiopsySLNBjkPrintedbyMinTangon3/26/202210:10:19AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalselineologyilmnoNDsitiveselineimagingtperformedcHEDRAININGentinellymphnodebiopsySLNBjkdexPRIMARYANDADJUVANTTREATMENTOFCLINICALN0DISEASEHEHEObservationmmnopuvantRTrdividualizedmarginsdmultimodalerapydeterminedommultidisciplinarysessmentincludingiationtorsqadversetorsqAdjuvantRTrinicalNMCCyfinicalNMCCyf•Multidisciplinaryconsultation•Nodedissectionand/orRTtothenodalbasinrvailables•ClinicaltrialvailableswithappropriateimmunopanelbObservationofthewithappropriateimmunopanelbSLNnegativeMayconsiderRTrtotheSLNnegativebasininhigh-riskpatientsatincreasedriskforafalseFootnotesonMCCANote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,03/24/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.MCC-2PrintedbyMinTangon3/26/202210:10:19AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexbSeePrinciplesofPathology(MCC-A).cImagingisencouragedinmostcasesofMCC.ImagingisindicatedwhenevermetastaticorunresectablediseaseissuspectedbasedonH&Pfindings.Occultmetastaticdiseasethatresultedinupstaginghasbeendetectedin12%–20%ofpatientspresentingwithoutsuspiciousH&Pfindings(SinghN,etal.JAmAcadDermatol2021;84:330-339).Whole-bodyPETwithfusedaxialimaging(CTorMR)orchest/abdomen/pelvisCTwithcontrast,withneckCTifprimarytumoronhead/neckorbrainMRIifclinicalsuspicion,maybeusefultoidentifyandquantifyregionalanddistantmetastases.Severalstudiesindicatewhole-bodyPETwithfusedaxialimagingismoresensitivefordetectingoccultmetastaticdiseaseatbaseline.Imagingmayalsobeusefultoevaluateforthepossibilityofaskinmetastasisfromanoncutaneousprimaryneuroendocrinecarcinoma(eg,smallcelllungcancer),especiallyincaseswhereCK20isnegative.ThemostreliablestagingtooltoidentifysubclinicalnodaldiseaseisSLNB.(GeorgeA,etal.NuclMedCommun2014;35:282-290;HawrylukEB,etal.JAmAcadDermatol2013;68:592-599;SivaS,etal.JNuclMed2013;54:1223-1229).fCriteriafor"LocalMCConly"arediseaselimitedtotheprimarytumor,withnoevidenceofin-transit,nodal,ordistantdisease.gTarabadkarE,etal.JAmAcadDermatol2021;84:340-347.hBaselineriskfactors:largerprimarytumor(>1cm);chronicT-cellimmunosuppression,HIV,CLL,solidorgantransplant;head/neckprimarysite;lymphovascularinvasionpresent.iSeePrinciplesofExcision(MCC-C).Inselectedcasesinwhichcompletesurgicalexcisionisnotpossible,surgeryisrefusedbythepatient,orsurgerywouldresultinsignificantmorbidity,radiationmonotherapymaybeconsidered.SeePrinciplesofRadiationTherapy(MCC-B).jConsiderempiricradiationtherapy(RT)tothenodalbasinwhen:1)theaccuracyofSLNBmayhavebeensubjecttoanatomiccompromise(lymphomainvolvednodes,orhistoryofremotelymphnodeexcision);2)whentheriskoffalse-negativeSLNBishighduetoaberrantlymphnodedrainageandpresenceofmultipleSLNbasins(suchasinhead&neckormidlinetrunkMCC);or3)whenidentifiedbylymphoscintigraphyincasesofprofoundimmunosuppression(ie,solidorgantransplantrecipients).SeePrinciplesofRadiationTherapy(MCC-B).kSLNBisanimportantstagingtool.ThisprocedureandsubsequenttreatmentimpactsregionalcontrolforpatientswithpositiveSLNs,buttheimpactofSLNBonoverallsurvivalisunclear.lSLNBistypicallyperformedatthistime.mNarrowexcisionmarginsminimizemorbidityandmicroscopicallypositivemarginsareacceptablewhenfollowedbyadjuvantRTtotheprimarysite.nMohsorotherformsofperipheralanddeepenfacemarginassessment(PDEMA),usingmarginssimilartowidelocalexcision(WLE),maybeappropriate.SeeNCCNGuidelinesforSquamousCellSkinCancer-PrinciplesofPDEMATechniquefordescriptionofPDEMA.oSurgicalmarginsshouldbebalancedwithmorbidityofsurgery.Ifappropriate,avoidunduedelayinproceedingtoRT.SeePrinciplesofExcision(MCC-C).pGoalshouldbeprimarytissueclosuretoallowforinitiationofadjuvantRT(ifneeded)within3–4weeks.qPost-excisionadverseriskfactorsincludepositiveornarrowlyclearmargins,orlymphovascularinvasionorpositiveSLNB.rSeePrinciplesofRadiationTherapy(MCC-B).sAdjuvantchemotherapymaybeconsideredinselectclinicalcircumstances;however,availableretrospectivestudiesdonotsuggestsurvivalbenefitforadjuvantchemotherapy.Nodataareavailabletosupporttheadjuvantuseofimmunotherapyoutsideofaclinicaltrial.SeePrinciplesofSystemicTherapy(MCC-D).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.MCC-2AVersion2.2022,03/24/2022©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.lowuplinicalNPrintedbyMinTangon3/26/202210:10:19AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.lowuplinicalNdexPRIMARYANDADJUVANTTREATMENTOFCLINICALN+DISEASEscHEMCCNDHENore•Fine-needleore•Immunopanelb•Multidisciplinaryconsultation•Nodedissectionand/orRTr•ClinicaltrialforadjuvanttherapyespreferredesnsiderCC SeeCCeNpathwayillanceonalpsyub

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