NCCNClinicalPracticeGuidelinesinOncologyNCCNGuidelines?)WilmsTumor(Nephroblastoma)Version2.2021—June17,2021NCCN.orgVersion2.2021,06/17/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.esPanelDisclosuresPrintedbyMinTangon9/2/202110:23:18AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2021NationalComprehensiveCancerNetwork,Inc.,AllesPanelDisclosures*FrankBalis,MD/Chair€Σ*DanielM.Green,MD/ViceChair€St.JudeChildren’sResearchHospital/TheUniversityofTennesseeClarkeAnderson,MD€?CityofHopeNationalMedicalCenterShellyCook,MD≠UniversityofWisconsinCarboneCancerCenterJasremanDhillon,MD≠M(fèi)offittCancerCenterKennethGow,MD,MHA€?SeattleCancerCareAllianceSusanHiniker,MD§RamaJasty-Rao,MD€UniversityofMichiganRogelCancerCenterChiLin,MD,PhD§Fred&PamelaBuffettCancerCenterHaroldLovvornIII,MD?Vanderbilt-IngramCancerCenterIainMacEwan,MD§cerCenterJulianMartinezAgostoMD,PhD€*ElizabethMullen,MD€ErinS.Murphy,MD§hensiveCancerCenterMDDanielRhee,MD,MPH€?kinsitkaMDMPHElisabeth(Lisa)Tracy,MD?TamaraVern-Gross,DO§MichaelF.Walsh,MD€?*AmyWalz,MD€*JonathanWickiser,MD€?CenterMatthewZapala,MD,PhD§UCSFHelenDillerFamilyCenterHughesPhDdiMSc?Hematology/Hematologyoncology€PediatriconcologyΣPharmacologyPrintedbyMinTangon9/2/202110:23:18AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2021NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexClinicalTrials:NCCNbelievesthatthebestmanagementforClinicalTrials:NCCNbelievesthatthebestmanagementforanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.FindanNCCNMemberInstitution:/home/member-institutions.NCCNCategoriesofEvidenceandConsensus:Allrecommendationsarecategory2Aunlessotherwiseindicated.SeeNCCNCategoriesofEvidenceandConsensus.aryoftheGuidelinesUpdatesNTROlEvaluationandInitialTreatmentWILMSumorWILMSILMSsectableUnilateralFHWTwithNoPredisposingConditionWILMSilateralFHWTwithPredisposingConditionWILMSnilateralFHWTwithPredisposingConditionWILMSBilateralFHWTwithorWithoutPredisposingConditionWILMScBilateralFHWTwithorWithoutPredisposingConditionWILMSPrinciplesofAbdominalMassEvaluation(WILMS-A)PrinciplesofImaging(WILMS-B)PrinciplesofPathology(WILMS-C)PrinciplesofSurgery(WILMS-D)PrinciplesofBiopsy(WILMS-E)RiskAssessmentforFHWT(WILMS-F)PrinciplesofChemotherapy(WILMS-G)PrinciplesofRadiationTherapyforFHWT(WILMS-H)SyndromesandCongenitalAnomaliesAssociatedwithWilmsTumor(WILMS-I)pCOGStagingofWilmsTumorSTTheNCCNGuidelinesareastatementofevidenceandconsensusoftheauthorsregardingtheirviewsofcurrentlyacceptedapproachestotreatment.AnyclinicianseekingtoapplyorconsulttheNCCNGuidelinesisexpectedtouseindependentmedicaljudgmentinthecontextofindividualclinicaltancestodetermineanypatientscareortreatmentTheNationalComprehensiveCancerNetworkNCCNmakesnorepresentationsorwarrantiesofanykindregardingtheircontentuseorapplicationanddisclaimsanyresponsibilityfortheirapplicationoruseinanyway.TheNCCNbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.?2021.Version2.2021,06/17/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.UPDATESVersion2.2021,06/17/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.PrintedbyMinTangon9/2/202110:23:18AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2021NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexUpdatesinVersion2.2021oftheNCCNGuidelinesforWilmsTumorfromVersion1.2021include:MS-1TheDiscussionsectionhasbeenupdatedtoreflectthechangesinthealgorithmPrintedbyMinTangon9/2/202110:23:18AM.Forpersonaluseonly.Notapprovedfordistribution.Copyright?2021NationalComprehensiveCancerNetwork,Inc.,AllRightsReserved.dexINTRODUCTIONTOWILMSTUMORAllpatientswithsuspectedWilmstumor(WT)shouldbemanagedbyamultidisciplinaryteamwithexperiencemanagingrenaltumors;consultingapediatriconcologistisstronglyencouraged.TheNCCNGuidelinesforWilmsTumor(Nephroblastoma)onlyaddressfavorablehistologyWilmstumor(FHWT)atthistime.EpidemiologyofWilmsTumor?WTaccountsfor5%ofchildhoodcancersandisthemostcommonprimaryrenaltumorinchildren(accountsfor>90%ofrenaltumorsinpatients<20years).Five-yearsurvivalforthesepatientsis>90%withappropriatetreatment.However,outcomeofsomegroups,particularlythosewithdiffuseanaplasticWT,remainspoor.ThisguidelinedoesnotincludeanaplasticWTatthistime.?IncidenceofWTishighestamongAfricanAmericanchildren,followedbyCaucasianchildren,andchildrenofAsiandescenthavethelowestincidence.1>75%ofWTpresentbetween1–5years(mostcommonly3years).2?Mostpatientshaveasolitarytumoratpresentation.However,5%–13%havebilateraltumors,and10%havemultifocaltumorsinasinglekidney.3-6pForunilateraltumors,themedianageatdiagnosisis35monthsforboys,and42monthsforgirls.1pForbilateraltumors,themedianageatdiagnosisis23monthsforboys,and28.5monthsforgirls.1lPresentation?Mostpatientspresentwithabdominaldistentionand/orpresenceofanabdominalmass(83%)withorwithoutabdominalpain(37%),fever(23%),hematuria(21%–25%),andhypertension(20%–25%).Lesscommonsymptomsinclude:varicocele,hernia,enlargedtesticle,congestiveheartfailure,hypoglycemia,Cushingsyndrome,pleuraleffusion,andacuteabdomen.?Ahealthy-appearingchildismorelikelytohaveWT,whereasanill-appearingchildmayhaveneuroblastoma.?Calcificationofthetumorappearsinapproximately5%–10%ofWTs,versusapproximately60%–70%ofneuroblastomas.?Almost10%ofpatientswithWThavecoagulopathy(acquiredVonWillebranddisease).7-9?Mostcommonsitesofhematogenousmetastasesinclude:lung(81%),lungandliver(15%),other(4%).10Spreadtoregionallymphnodes(LNs)alsooccurs.?WTisassociatedwithgeneticpredispositionsyndromes,suchasBeckwith-Wiedemannsyndrome(macroglossia,hemihyperplasia,gigantism,andumbilicalhernia);WAGRsyndrome(WT,aniridia,genitourinaryabnormalities,andrangeofdevelopmentaldelay);andDenys-Drashsyndrome(malepseudohermaphroditismandglomerulopathy),in10%–15%ofcases.11-15?Aniridiaispresentin1%ofchildrenwithWT,andhemihyperplasiaappearsin2%–3%ofWTpatients.15-17?Genitourinarymalformations(ie,cryptorchidism,hypospadias,fused[horseshoe]kidneys)arefoundin5%ofpatientswithWT.17,18?Ifpredispositionispresent,routinescreeningforWTisrecommendedwithphysicalexamandrenalUSevery3monthsuntilatleast8yearsofage.19,20?Childrenwithmultifocal/bilateraldiseasepresentatayoungeragethanchildrenwithunilateraldisease,andareoftenidentifiedaspartofasurveillanceprogram.19,20Treatment?TreatmentforWTrangesfromobservationaftersurgeryonly,tointensivechemotherapy,radiation,andsurgery,dependingonwhethertheWTisunilateralorbilateral,localstage,presenceofmetastases,patientage,tumorweight,biologicriskfactors,histology,andclinicalresponsetotherapy.?ConsultingaradiationoncologistisrecommendedattimeofdiagnosisofWT.?Studiesoflong-termsurvivorsshowthesetherapiesareeffective;however,judicioususeofavailabletherapiesisnecessarytomaximizecurewhileminimizinglong-termtoxicities.?Appropriateassignmentoftherapytobalancethesegoalsemploysanevolvingsystemofriskstratification.?ReferraltoCancerPredispositionConsultationisappropriateforallpatientswithWTandstronglyencouragedforpatientswithmultifocalorbilateralWT.?Recommendreferraltoinfertilityrisk/fertilitypreservationcounselingforallpatientstreatedwithchemotherapy;stronglyencouragepriortotreatmentwithregimenMorwholeabdominalirradiation(WAI).21,22Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.INTRO-1Version2.2021,06/17/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.MAnoverviewoftheclinicalandmoleculargeneticsofWilmstumorMedPediatrOncolBlakelyMLRitcheyMLControversiesinthemanagementofWilmstumor.MAnoverviewoftheclinicalandmoleculargeneticsofWilmstumorMedPediatrOncolBlakelyMLRitcheyMLControversiesinthemanagementofWilmstumor.SeminPediatrSurg2001;10:127-131.talHyperdiploidyandchromosomalrearrangementsdefinetheanaplasticvariantofWilmstumorJClinOncolRiccardiVMHittnerHMFranckeUetalTheaniridiaWilmstumorassociationThecriticalroleofchromosomebandp13.CancerGenet1980;2:131-137.PalmerNEvansAETheassociationofaniridiaandWilmstumormethodsofsurveillanceanddiagnosisMedPediatrOncol-75.endergrassTWCongenitalanomaliesinchildrenwithWilmstumoranewsurveyCancerBreslowNEBeckwithJBEpidemiologicalfeaturesofWilmstumorresultsoftheNationalWilmsTumorStudyJNatlCancerInst436.19BrioudeF,KalishJM,MussaA,etal.Expertconsensusdocument:Clinicalandmoleculardiagnosis,screeningandmanagementofBeckwith-Wiedemannsyndrome:aninternationalconsensusstatement.NatRevEndocrinol2018;14:229-249.20KalishJM,DorosL,HelmanLJ,etal.SurveillancerecommendationsforchildrenwithovergrowthsyndromesandpredispositiontoWilmstumorsandhepatoblastoma.ClinCancerRes2017;23:e115-e122.21PracticeCommitteeoftheAmericanSocietyforReproductiveMedicine.Fertilitypreservationinpatientsundergoinggonadotoxictherapyorgonadectomy:acommitteeopinion.FertilSteril2019;112:1022-1033.22LeeSJ,SchoverLR,PartridgeAH,etal.AmericanSocietyofClinicalOncologyrecommendationsonfertilitypreservationincancerpatients.JClinOncol2006;24:2917-2931.dexINTRODUCTIONTOWILMSTUMORREFERENCES1Steliarova-FoucherE,ColombetM,RiesLAG,etal.Internationalincidenceofchildhoodcancer,2001-10:apopulation-basedregistrystudy.LancetOncol2017;18:719-731.2HowladerN,NooneAM,KrapchoM,etal.SEERCancerStatisticsReview,1975-2017,basedonNovember2019SEERdatasubmission,postedtotheSEERwebsite,April2020.Bethesda,MD:NationalCancerInstitute;2020.3D'AngioGJ.NationalWilms’TumorStudy,Seattle,WA:NWTSDataandStatisticalCenter:1991[InformationalBulletin#19].4BreslowNE,ChurchillG,NesmithB,etal.ClinicopathologicfeaturesandprognosisforWilms’tumorpatientswithmetastasesatdiagnosis.Cancer1986;58:2501-2511.5HadleyGP,JacobsC.TheclinicalpresentationofWilms’tumourinblackchildren.SAfrMedJ1990;77:565-567.6EhrlichP,ChiYY,ChintagumpalaMM,etal.Resultsofthefirstprospectivemulti-institutionaltreatmentstudyinchildrenwithbilateralWilmstumor(AREN0534):AreportfromtheChildren'sOncologyGroup.AnnSurg2017;266:470-478.7GreenDM.Diagnosisandmanagementofmalignantsolidtumorsininfantsandchildren.1985.MartinusNijhoffPublishing,Boston,MA.8MaasMH,CransbergK,vanGrotelM,etal.Renin-inducedhypertensioninWilmstumorpatients.PediatrBloodCancer2007;48:500-503.9MarsdenHB,LawlerW,KumarPM.Bonemetastasizingrenaltumorofchildhood:morphologicalandclinicalfeatures,anddifferencesfromWilms’tumor.Cancer1978;42:1922-1928.morPredispositionGeneReviewsInternethttpswwwncbinlmnihgovbooksNBKtcheyMLetalHepaticmetastasisatdiagnosisinpatientswithWilmstumorisnotanindependentadversemorPredispositionGeneReviewsInternethttpswwwncbinlmnihgovbooksNBKNote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.INTRO-1AVersion2.2021,06/17/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.AbdominalpelvicCTwithtorMRIcd?ChestCTcwithoutcontrastessmentforcongenitalsereeningforpredispositioneINITIALEVALUATIONbFINDINGSINITIALTREATMENTumorikelyBenignconditionsinclude:adrenalAbdominalpelvicCTwithtorMRIcd?ChestCTcwithoutcontrastessmentforcongenitalsereeningforpredispositioneINITIALEVALUATIONbFINDINGSINITIALTREATMENTumorikelyBenignconditionsinclude:adrenalhemorrhage,angiomyolipoma,cysticnephroma,dysplastickidney,hydronephrosis,metanephrictumors(adenoma,stromaltumor,adenofibroma),multicystickidneydisease,nephroblastomatosis,polycystickidneydisease,renalhemorrhage,renalveinthrombosisatealistriatelistNGuidelines,ifablerUnilateralWILMS)rBilateralWILMS)malignanttumorlikelyepatoblastomaplasticbluecelltumororotherrarenancyrenaltumorBilateralrenaltumorswithorwithoutdexPRESENTATIONAbdominalswellingand/orsuspiciousmasshmassa(firm,hmassaabdominalpain,fever,?H&P(includinggeneralhealth),bloodpressure,andpriormedicalandfamilyhistory?CBCanddifferential,comprehensivemetabolicpanel,andurinalysis(UA);toruleoutneuroblastoma,considerurinehomovanillicacid(HVA)andvanillylmandelicacid(VMA)?Abdominalultrasound(US)c?Abdominalultrasound(US)ceConditionsthatpredisposetothedevelopmentofWTincludegeneticdisorderssuchasBeckwith-Wiedemann,WAGR,Denys-Drash,Frasier,andPerlmansyndromes;contralateralnephrogenicrestsinchildren<12months.TenpercentidvigorousorfrequentpalpationbSeePrinciplesofAbdominalMassEvaluation(WILMS-A).cSeePrinciplesofImaging(WILMS-B).dCTwithmultiplanarreconstructionorMRIwithcontrastisrecommended;MRImaybeusedwhenbilateraldiseaseissuspectedasitmayhelptodistinguishphrogenicrestsandWTto20%ofWToccurinchildrenwithpredisposingconditions.ChildrenwithknownidvigorousorfrequentpalpationbSeePrinciplesofAbdominalMassEvaluation(WILMS-A).cSeePrinciplesofImaging(WILMS-B).dCTwithmultiplanarreconstructionorMRIwithcontrastisrecommended;MRImaybeusedwhenbilateraldiseaseissuspectedasitmayhelptodistinguishphrogenicrestsandWTNote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.WILMS-1Version2.2021,06/17/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.nPerformmolecularanalysistoidentifylossofheterozygosityLOH)of1p,16q,11p,andextendingabovethehepaticveins,bilateraltumors,involvementofsurroundingorgans,orlBiopsyisrecommended(preferred)fordiagnosisandsothatnPerformmolecularanalysistoidentifylossofheterozygosityLOH)of1p,16q,11p,andextendingabovethehepaticveins,bilateraltumors,involvementofsurroundingorgans,orlBiopsyisrecommended(preferred)fordiagnosisandsothatmolecularbiomarkertestingfromproliferatingnephrogenicrests.dexFINDINGSINITIALTREATMENTUnilateralumorTumorresectablePrimarynephrectomysamplinghijsamplinghijkionofFHWTnSeeAdjuvantTreatmentforUnilateralFHWT(WILMS-3)reatmentforUnresectableUnilateralhNoPredisposingionWILMSwhenpossiblelwhenpossiblel(preferred)ionofFHWTnffTumorbiopsynotpossibleresectiongnotindicatedmyresectiongnotindicatedmSeeNeoadjuvantTreatmentforUnilateralRenalTumorwithPredisposingConditions(WILMS-6)renaltumorsWithorwithoutp DelaytumorndicatedmTumorbiopsyndicatedmSeeNeoadjuvantTreatmentforInitiallyUnresectableBilateralRenalTumor(WILMS-8)eConditionsthatpredisposetothedevelopmentofWTincludegeneticdisorderssuchasBeckwith-Wiedemann,WAGR,Denys-Drash,Frasier,andPerlmansyndromes;contralateralnephrogenicrestsinchildren<12months.Tenpercentto20%ofWToccurinchildrenwithpredisposingconditions.ChildrenwithknownpredisposingconditionsshouldbescreenedforWTwithPEandabdominalUSevery3monthsuntilatleast8yearsofage.SeeSyndromesandCongenitalAnomaliesAssociatedwithWilmsTumor(WILMS-I).ConsidergermlinetestingforpatientswithphysicalfindingsconsistentwithafRenaltumorsfRenaltumorsmaybeunresectableatdiagnosisbecauseoftumorsize,tumorthrombusgFortumors<2cm,considerclosegFortumors<2cm,considerclosesurveillancegiventhechallengeofdifferentiatingWThNephrectomyandregionalLNsamplingarerecommendedasinitialtherapyforresectabletumors.LNsamplingMUSTbeperformedforadequatestaging;recommendobtainingminimum>5(nodes)fromareasinrenalhilumanatomicallyexpectedtorepresentnodesiSeePrinciplesiSeePrinciplesofPathology(WILMS-C).GStagingofWilmsTumorSTjGStagingofWilmsTumorSTmBiopsyisnotindicatedforpatientswithbilateralWilmsand/orpredisposingsyndrome.canbedonemBiopsyisnotindicatedforpatientswithbilateralWilmsand/orpredisposingsyndrome.1qgain.IftumorisnotWT,refertoappropriatespecialistorNCCNGuidelines,ifavailable.Othermalignantrenaltumorsincludeclearcellsarcomaofthekidney,rhabdoidtumor,congenitalmesoblasticnephroma,renalcellcarcinoma,orrenalmedullarycarcinoma.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2021,06/17/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.WILMS-2itableforreductionoftherapyobservationPrintedbyMinTangon9/2/202110:23:18AM.Forpersonaluseonly.Notapprovedfordistribution.CopyrightitableforreductionoftherapyobservationdexFINDINGSINITIALRISKGROUPoVerylowrisk(VLR)Lowrisk(LR)Standardrisk(SR)Higherrisk(HR)INITIALTHERAPYpMOLECULARRESULTSbiomarkersADJUVANTCHEMOTHERAPYObservationationorimprinting(LOI)positiveorRegimenimprinting(LOI)positiveorRegimenEE4Ap,qpositiveNoLOHatboth1pand16qLOH1pand16qpositiveContinueRegimenEE4ApContinueRegimenEE4ApgimenDDAgimenDDApgimenDDAptchtorNoLOHgimenDDAptchtorLOH1LOH1pand16qpositiveRegimenDD4ApWILMSRADIATIONTHERAPYs,tomenforlocalstageIIIoInitialRiskGroupbasedonhistology,stage,age,andtumorweight.SeeRiskwithoutadjuvantchemotherapy).rRegimenMhasagreaterriskofincreasedtoxicityandlateeffects,includingsecondcancersandinfertilityrelatedtocyclophosphamideandetoposide.ThereareissueswiththehistoricalcomparisongroupthathasbeenusedtojustifysSeePrinciplesofRadiationsSeePrinciplesofRadiationTherapyforFHWT(WILMS-H).tRTisoftengiven10to14daysaftersurgery.However,considerpatientfactorswhendecidingaboutthetimingofRT(eg,ageofpatient,needtoassessresponseoflungmetastasestochemotherapy,whengivingwholeabdomenandwholelungRT).LocalstageIIIreferstostagingattheprimarytumorregardlessofmetastases.Note:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.Version2.2021,06/17/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.WILMS-3AREN0533,butresultshavenotbeenpublished.vPatientswith1qgain,noLOH,andCRoflungmetastasesatweek6shouldNote:Allrecommendationsarecategory2AunlessotherwiseindicatedAREN0533,butresultshavenotbeenpublished.vPatientswith1qgain,noLOH,andCRoflungmetastasesatweek6shouldNote:Allrecommendationsarecategory2Aunlessotherwiseindicated.ClinicalTrials:NCCNbelievesthatthebestmanagementofanypatientwithcancerisinaclinicaltrial.Participationinclinicaltrialsisespeciallyencouraged.dexFINDINGSprimarynephrectomy,RINITIALRISKGROUPoINITIALTHERAPYpMOLECULAR/IMAGINGRESULTS(WEEK6)RADIATIONTHERAPYs,RADIATIONTHERAPYs,tCHEMOTHERAPYNoLOHatboth1pand16q,no1qgain,andcompleteresponse(CR)oflungmetastasesatweek6LOH1pand16qpositiveor1qgainpositive,orslowincompleteresponse(SIR)oflungmetastasesatweek6ContinueRegimenDD4ApenforlocalstageIIInowholelungek??FlankorwholeabdomenforlocalstageWholelungContinueRegimenDD4Ap,vrorrgimenDDApContinueRegimenDD4Ap,x?FlankorwholeabdomenforlocalstageIII?Wholelungforlungmetastases?OthersitesoInitialRiskGroupbasedonhistology,stage,age,andtumorweight.SeeRiskAssessmentforFHWT(WILMS-F).pSeePrinciplesofChemotherapyforFHWT(WILMS-G).rRegimenMhasagreaterriskofincreasedtoxicityandlateeffects,includingsecondcancersandinfertilityrelatedtocyclophosphamideandetoposide.ThereareissueswiththehistoricalcomparisongroupthathasbeenusedtojustifyaugmentingtherapywithRegimenM.sSeePrinciplesofRadiationTherapyforFHWT(WILMS-H).tRTisoftengiven10to14daysaftersurgery.However,considerpatientfactorswhendecidingaboutthetimingofRT(eg,ageofpatient,needtoassessresponseoflungmetastasestochemotherapy,whengivingwholeabdomenandwholelungRT).LocalstageIIIreferstostagingoftheprimarytumorregardlessofuIfuIffeasibleresectmetastatictumorsatthetimeofprimarynephrectomy.continueonRegimenDD4Abutshouldhavewholelungirradiation(WLI).OmissionofWLIforpatientswithCRoflungmetastasesatweek6and1qgainisnotrecommendedbecauseoflowerevent-freesurvival(EFS;57%).xPatientswithextrapulmonarymetastaseswereswitchedtoRegimenMonxPatientswithextrapulmonarymetastaseswereswitchedtoRegimenMonVersion2.2021,06/17/21?2021NationalComprehensiveCancerNetwork(NCCN),Allrightsreserved.NCCNGuidelinesandthisillustrationmaynotbereproducedinanyformwithouttheexpresswrittenpermissionofNCCN.WILMS-4 tasesuenx?tasesHYPERLINK\l"_b