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NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines®)PenileCancerersionJanuaryVersion2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:54:04AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dex*ThomasW.Flaig,MD†/ChairUniversityofColoradoCancerCenter*PhilippeE.Spiess,MD,MS¶ϖ/ViceChairMoffittCancerCenterrnMDnterNeerajAgarwal,MD‡†HuntsmanCancerInstituteattheUniversityofUtahMBAeephenABoorjianMDCancerCenterMarkK.Buyyounouski,MD,MS§StanfordCancerInstituteKevinChan,MD¶CityofHopeNationalMedicalCenterSamChang,MD,MBA¶Vanderbilt-IngramCancerCenterTerenceFriedlander,MD†UCSFHelenDillerFamilyComprehensiveCancerCenterchardEGreenbergMDerCenterruMDComprehensiveCancerCenterloanKetteringCancerCenteresPanelDisclosuresJeanHoffman-Censits,MD†TheSidneyKimmelComprehensiveCancerCenteratJohnsHopkinsAmarU.Kishan,MD§UCLAJonssonComprehensiveCancerCenterShilajitKundu,MD§RobertH.LurieComprehensiveCancerCenterofNorthwesternUniversitySubodhM.Lele,MD≠Fred&PamelaBuffettCancerCenterRonacMamtani,MD†AbramsonCancerCenterVitalyMargulis,MDϖUTSouthwesternSimmonsComprehensiveCancerCenterOmarY.Mian,MD,PhD§CaseComprehensiveCancerCenter/UniversityHospitalsSeidmanCancerCenterandClevelandClinicTaussigCancerInstituteJeffMichalski,MD,MBA§SitemanCancerCenteratBarnes-JewishHospitalandWashingtonUniversitySchoolofMedicineJeffreyS.Montgomery,MD,MHSAϖUniversityofMichiganRogelCancerCenterLakshminarayananNandagopal,MD†O'NealComprehensiveCancerCenteratUABLanceC.Pagliaro,MD†MayoClinicCancerCenterMamtaParikh,MD,MS†AnthonyPatterson,MDϖSt.JudeChildren’sResearchHospital/TheUniversityofTennesseeeCenterElizabethR.Plimack,MD,MS†ÞFoxChaseCancerCentereOhioStateUniversityComprehensivecerCenterJamesCancerHospitaldSoloveResearchInstituteMarkA.Preston,MD,MPHϖDana-Farber/BrighamandWomen’senterKyleRichards,MDϖUniversityofWisconsinCarboneCancerCenterWadeJ.Sexton,MDϖMoffittCancerCenterArleneO.Siefker-Radtke,MD†TheUniversityofTexasJonathanTward,MD,PhD§HuntsmanCancerInstituteattheUniversityofUtahJonathanL.Wright,MD,MSϖFredHutchinsonCancerResearchCenter/SeattleCancerCareAllianceiPhDrlyJCassaraMSc‡Hematology/HematologyoncologyÞInternal‡Hematology/HematologyoncologyÞInternalmedicine†Medicaloncology≠Pathology§Radiotherapy/Radiationoncology¶Surgery/SurgicalOncologyϖUrology*DiscussionwritingcommitteememberVersion2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.anelMembersoftheGuidelinesUpdatesnClinicalDiagnosisPNanelMembersoftheGuidelinesUpdatesnClinicalDiagnosisPNNnPalpableInguinalLymphNodesPNalpableNonBulkyInguinalLymphNodesPNlpableBulkyInguinalLymphNodesPNargedPelvicLymphNodesPNnceSchedulePNentofRecurrentDiseasePNmentofMetastaticDiseasePNPrinciplesofPenileOrgan-SparingApproaches(PN-A)PrinciplesofSurgery(PN-B)PrinciplesofRadiotherapy(PN-C)PrinciplesofSystemicTherapy(PN-D)PrinciplesofImaging(PN-E)Staging(ST-1)dexFindanNCCNMemberInstitution:/home/member-institutions.dNCCNCategoriesofPreference:Allrecommendationsareconsideredappropriate.SeeNCCNCategoriesofPreference.TheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatmentAnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualstancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanywayTheNCCNationalComprehensiveCancerNetworkAllrightsreservedTheNCCNGuidelinesandtheillustrationshereinmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.©2022.Version2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:54:04AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexsionoftheNCCNGuidelinesforPenileCancerfromVersioninclude•Thediscussionhasbeenupdatedtoreflectthechangesinthealgorithm.sionoftheNCCNGuidelinesforPenileCancerfromVersioninclude•Intermediate-/High-risktreatmentmodified:Bilateralinguinallymphnodedissection(ILND)PN-4High-riskprimarylesiontreatmentmodified:pBilateralILNDpConsiderneoadjuvantTIP(paclitaxel,ifosfamide,cisplatin)chemotherapyfollowedbyILNDPN-5•Unilaterallymphnodes≥4cm(mobile)pPositivepercutaneouslymphnodebiopsy,treatmentmodified:Cisplatin-basedTIPNeoadjuvantTIPchemotherapyfollowedbyILND(preferred),considerPLNDorILND(preferred),considerPLND(inpatientsnoteligibleforcisplatin-basedchemotherapyTIP)•Unilaterallymphnodes(fixed)orbilaterallymphnodes(fixedormobile)pPositivepercutaneouslymphnodebiopsy,treatmentmodified:NeoadjuvantTIPchemotherapyPN-6•Treatmentforsurgicalcandidatemodified:NeoadjuvantTIPchemotherapyPN-7•Thispagehasbeenextensivelyrevised.PN-D2of4•Subsequent-lineSystemicTherapyforMetastatic/RecurrentDiseasetablemodifiedpPembrolizumab,ifunresectableormetastatic,microsatelliteinstability-high(MSI-H)ormismatchrepair-deficient(dMMR)tumorthathasprogressedfollowingpriortreatmentandnosatisfactoryalternativetreatmentoptions,oriftumormutationalburden-high(TMB-H),TMB≥10mut/Mbinpatientswhohaveprogressedonpreviouslyapprovedlinesoftherapy.•Referenceadded:MarabelleA,etal.LancetOncol2020;10:1353-1365.INTROVersion2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:54:04AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexINTRODUCTIONNCCNandtheNCCNPenileCancerPanelbelievethatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.HPcpeniletraumaalcircumcisiontobaccouselichensclerosus,exuallyansmitteddiseasePrintedbyMinTangon3/14/20227:54:04AM.Forpersonaluseonly.NotapprovedforHPcpeniletraumaalcircumcisiontobaccouselichensclerosus,exuallyansmitteddiseasedexPRIMARYEVALUATIONCLINICALDIAGNOSISPRIMARYTREATMENTTopicaltherapybWideWidelocalexcisionbLasertherapyb(category2B)CompleteCompleteglansectomyb(category2B)MohssurgeryinselectcasesbyBtoftofuinalhologypapillaryousptootherstructuresalcorporaspongiosacavernosa,and/ortologicdiagnosisptootherstructuresalcorporaspongiosacavernosa,and/ortologicdiagnosissurrentdiseaseseePNoricdiseaseseePNaTheseGuidelinesarefortreatmentofsquamouscellcarcinomaofthepenis.plesofPenileOrganSparingApproachesPNANote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PN-1RadiotherapydcategoryB)Chemoradiotherapyd,e(category3)PrintedbyMinTangon3/14/20227:54:04AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,RadiotherapydcategoryB)Chemoradiotherapyd,e(category3)dexPATHOLOGICDIAGNOSISTorgreaterPRIMARYTREATMENTWidelocalexcisionbycdGlansectomyinselectcasesberyinselectcasesbcategoryBLasertherapybcategoryB)RadiotherapydcategoryB)SeeManagementofuinalLasertherapybcategoryB)RadiotherapydcategoryB)WidelocalexcisionbPartialpenectomyc,dRadiotherapydcategoryB)Chemoradiotherapyd,e(category3)ycdSeeManagementRadiotherapydcategoryB)Chemoradiotherapyd,e(category3)ycdbSeePrinciplesofPenileOrgan-SparingApproaches(PN-A).cSeePrinciplesofSurgery(PN-B).dSeePrinciplesofRadiotherapyPN-C).eSeePrinciplesofSystemicTherapy(PN-D).Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:54:04AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexMANAGEMENTOFNON-PALPABLEINGUINALLYMPHNODESNODALTUSNODALTUSIMAGINGBASEDONPRIMARYLESIONIntermediate/Highrisk•T1b•AnyT2orgreaterCross-sectionalpelvisgimagingofpelvisgTREATMENTcveillanceSeePNBilateralinguinal(ILND)h,i(ILND)h,iorkkeillancecSeePrinciplesofSurgery(PN-B).fTaverrucouscarcinomaisbydefinitionawell-differentiatedtumor.Therefore,onlysurveillanceoftheinguinallymphnodesisrequired.gCross-sectionalimagingmayincludeCT,MRI,PET/CT,and/orchestx-ray.Whenappropriate,imagingshouldbedonewithcontrastunlesscontraindicated.SeePrinciplesofImaging(PN-E).hAmodified/superficialinguinaldissectionwithintraoperativefrozensectionisanacceptablealternativetostagetheinguinallymphnodes.iConsiderprophylacticexternalbeamradiationtherapy(EBRT)(category2B)toinguinallymphnodesinpatientswhoarenotsurgicalcandidatesorwhodeclinesurgicalmanagement.jDSNBisrecommendedprovidedthetreatingphysicianhasexperiencewiththismodality.kIfpositivelymphnodesarefoundonDSNB,ILNDisrecommended.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.cSeePrinciplesofSurgery(PN-B).SurveillancePrintedbyMinTangon3/14/20227:54:04AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightscSeePrinciplesofSurgery(PN-B).SurveillancedexMANAGEMENTOFPALPABLENON-BULKYINGUINALLYMPHNODESNODALTUSIMAGINGRISKNODALTUSIMAGINGIMAGINGFINDINGSIMAGINGFINDINGSExcisionalbiopsyveorUnilaterallesionbiopsypprimaryUnilaterallesionbiopsypprimarylymphnodePelviclymphnodetradiotherapydpelvictradiotherapydotherapyde(category2otherapyderyBryBILND•Chemoradiotherapyd,e(category2B)onalfUnilaterallymphnode(s)≥4•Chemoradiotherapyd,e(category2B)onalfdomen orofPalpabledomeneslUnilaterallymphnode(s)<4cm(fixed)esltherapyeyBtherapyeyBBilaterallymphnodes(fixedormobile)(PN-5)EnlargedpelviclymphnodesEnlargedpelviclymphnodesEnlargedPelvicdSeePrinciplesofRadiotherapy(PN-C).eSeePrinciplesofSystemicTherapy(PN-D).gCross-sectionalimagingmayincludeCT,MRI,PET/CT,and/orchestx-ray.Whenappropriate,imagingshouldbedSeePrinciplesofRadiotherapy(PN-C).eSeePrinciplesofSystemicTherapy(PN-D).lCT/MRIofpelviswithcontrastfornodalevaluationifdifficulttoassessonphysicalexam.mIfM1diseaseidentified,seeManagementofMetastaticDisease(PN-9).nThesizethresholdof4cmrepresentsthelargestdiameterofcontiguousinguinallymphnode(s)tissueasmeasuredoneitherphysicalexaminationand/oraxialimaging(CTorMRI)andsuspectedofharboringmetastaticdisease.oHigh-riskprimarylesion:T1,high-grade,lymphovascularinvasion,perineuralinvasion,>50%poorlyundifferentiated.pUltrasound-orCT-guidedbiopsyofmostaccessiblenode,inguinalorpelvic.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.rrhemoradiotherapydeorNegativeExcisionalNegativeSeeSurveillance(PN-7)PLNDc,q,r(preferred)SeeNoteligibleforneoadjuvantorSurveillancerrhemoradiotherapydeorNegativeExcisionalNegativeSeeSurveillance(PN-7)PLNDc,q,r(preferred)SeeNoteligibleforneoadjuvantorSurveillancechemotherapyRTc(PN-7)ormobile)PositivechemotherapyeResponseDc,q(preferred)dexMANAGEMENTOFPALPABLEBULKYINGUINALLYMPHNODESNeoadjuvantTIPwithviablediseasechemotherapyefollowedby•AdjuvantILND(preferred),considerchemotherapye(ifnot<4cm(fixed)Unilateral<4cm(fixed)UnilateralNegativeN-C).rhemoradiotherapyd,eeSeePrinciplesofSystemicN-C).rhemoradiotherapyd,erDatasuggestthatinthesettingofpositiveinguinallymphnodes,bilateralPLNDshouldbeperformed.Zargar-ShoshtariK,JUrol2015;194:696-701.nTherDatasuggestthatinthesettingofpositiveinguinallymphnodes,bilateralPLNDshouldbeperformed.Zargar-ShoshtariK,JUrol2015;194:696-701.lymphnode(s)tissueasmeasuredoneitherphysicalexaminationand/oraxialimaging(CTorMRI)andsuspectedofharboringmetastaticdisease.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.PN-5Version2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:54:04AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexMANAGEMENTOFENLARGEDPELVICLYMPHNODESNODESTATUSLYMPHNODESTREATMENTlymphsnshnicallyhnicallysibletififSeemanagementdependingoninguinallymphnodestatus:Non-PalpableInguinalLymphNodes(PN-3)orPalpableNon-BulkyInguinalLymphNodes(PN-4)orPalpableBulkyInguinalLymphNodes(PN-5)anceioneryqanceioneryquresponseonalpyeonalpyeesponseDiseaseesponseDiseasesiononManagementetastaticDiseasePNNon-Non-surgicalChemoradiotherapyd,eSeeSurveillance(PN-7)dSeePrinciplesofRadiotherapy(PN-C).eSeePrinciplesofSystemicTherapy(PN-D).gCross-sectionalimagingmayincludeCT,MRI,PET/CT,and/orchestx-ray.Whenappropriate,imagingshouldbedonewithcontrastunlesscontraindicated.SeePrinciplesofImaging(PN-E).mIfM1diseaseidentified,seeManagementofMetastaticDisease(PN-9).pUltrasound-orCT-guidedbiopsyofmostaccessiblenode,inguinalorpelvic.qConsiderpostoperativeradiotherapyorchemoradiotherapy(category2B).sOnCTorMRI,notpathologicstage.tIfnottechnicallyfeasible,PET/CTscancanbeusedtoevaluatelymphnodes.uConsolidationsurgeryconsistsofbilateralsuperficialanddeepILNDandunilateral/bilateralPLND.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon3/14/20227:54:04AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexSURVEILLANCESCHEDULEANATOMICSITEINITIALTREATMENTSURVEILLANCEwTopicalorlocaltherapyPartialorradicalpenectomy•Clinicalexamx,ypYears1–2:every3mo,thenpYears3–5:every6mo,thenpYears5–10:every12mo•Clinicalexamx,ypYears1–2:every6mo,thenpYears3–10:every12moncenceatherlocalorntsitesseeManagementofteasePNpYears1–2:every6mo,thenpYears3–4:every12mo•Clinicalexam,x,yCTabdomen/pelvisandchestradiographpYears1–2:every6mo,thenpYears3–4:every12mo•Clinicalexam,x,yCTabdomen/pelvis,andchestCTpYear1:every3mo,thenpYears2–4:every6movPatientsonactivesurveillanceofclinicallynegativenodesandatlowriskforinguinalmetastases.wSeeNCCNGuidelinesforSurvivorship.xClinicalexamincludesexaminationofthepenisandinguinalregion.yIfanabnormalclinicalexam,obesepatient,orprioringuinalsurgery,thenultrasound,CTwithcontrast,orMRIwithcontrastoftheinguinalregioncanbeconsidered.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.PN-7Version2.2022,1/26/2021©2022NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.otherapydePrintedbyMinTangon3/14/20227:54:04AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright©2022NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.otherapydedexMANAGEMENTOFRECURRENTDISEASERecurrenceofpenilelesionTreataccordingtorecurrencestageafterinitialpenile(SeePN-1andPN-2)sparingtreatmentanceancepN1 ILNDc ILNDcchemotherapyeorPositivellectomyrRTyBpN2-3or(category2B)yyeBhBhrBilateralLymphNodesFixedorMobile(PN-5)disease

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