StratégiesthérapeutiquedanslescancersdeprostateN+

StéphaneSupiot,OncologieRadiothérapie,ICONantes

Liend’intérêt

• Aucunenrapportaveccesujet

DéfinitioncancerdeprostateN1:uneentitérare?

12%des50000cancersdeprostatedétectéschaqueannée=6000cas/an

• TDMabdomen pelvis:adp >10mm?15mm?• IRMabdomenpelvis• Curageganglionnaire avortés=cN1?

• TEPFCH(+PSMA…)

http://seer.cancer.gov/statfacts/html/prost.html

Distinction

cN1• TDMleplussouvent• TEP?IRM?

pN1• Curageganglionnaire• +/- extensif• +/- prostatectomie

PatientscN1:

PatientscN1:pasdepreuvesdeniveau1del’utilitédela

chirurgieoudelaRT

Néanmoinsplusieurspreuvesindirectesetétudesnonrandomisées

Cancersdeprostatederisqueélevé:rôleindispensableRTHT

RT+HT>RTseule HT+RT>HTseule

Protocole SG(%)8-10ans

D'Amico,JAMA.2008

RT+/- HT6mois

74vs 61s

Roach,JCO2008

RT+/- HT4mois

43vs 34ns

Bolla,LancetOnc2010

RT+/- HT3ans

58vs 39s

Study Protocole OS(%)

Wildmarketal.(880pts)

MAB(3mo)+flutamide (cont)RT70Gy

29,639,4

p=0,004

Wardeet al.(1205pts)

Orchidectomieou ago LHRH(cont)RT65-69 Gy

1523

p=0,033

Mottetet al.(273pts)

Leuprorelin (3ans)RT70± 4Gy

71,571,4ns

Martin,Supiot,Berthold.Pharmacotherapeutic managementoflocallyadvancedprostatecancer:currentstatus.Drugs(2011)

OR:étudesfaitesàépoqueoùimageriemoinspréciseRôleRTsiN+d’emblée?

MorganetParker.Localtreatment ofmetastatic cancer--killing theseedordisturbing thesoil?.NatureReviewsClinical Oncology (2011)

Kprostatedehautrisque=Maladie

micrométastatique ?

Donnéesderegistre

DonnéesSEER1988-20061100patients

RT=meilleuresurviespécifique à10ans(63%vs50%,p<0,01)

Tward etal.Radiation therapy forclinically node-positiveprostate adenocarcinoma is correlated with improvedoverall andprostate cancer-specific survival.Pract RadiatOncol (2013)vol.3(3)pp.234-40

DonnéesSEER1995-2005patientscN1869 patients

Rusthoven etal.Theimpactofdefinitive localtherapy forlymph node-positive prostate cancer:apopulation-based study.IJROBP(2014)vol.88(5)pp.1064-73

DonnéesNationalCancerDataBase(NCI)636patients

survie à5ansdanslegroupeirradié(72%contre53%,p<0,001)

RT=+20%à5ans

Linetal.Androgen deprivation withorwithout radiation therapy forclinically node-positiveprostatecancer.JNCI(2015)vol.107(7)

DonnéesprospectiveSTAMPEDE

Jamesetal.Failure-FreeSurvival andRadiotherapy inPatientsWith Newly Diagnosed Nonmetastatic Prostate Cancer:DataFrom PatientsintheControl ArmoftheSTAMPEDETrial.JAMAOncol (2015)pp.1-10

177pts

Prostate74Gyin37fPelvisoptionnel :46-50Gy2Gy/fouSIB55Gy,37f

82%(58of71)prostate+pelvis,

Tolérance:Pasdetox dig G3

QuelleestlatoxicitédigestivedeRTganglionnaire?

• SansRCMI:toxicitéaiguë+++• AvecRCMI:peudetoxicité,

mêmeavecfortesdoses(ex:56Gy,28f/55,1Gy,29f)

• Bayley etal.Clinical application ofhigh-dose,image-guided intensity-modulated radiotherapy inhigh-risk prostate cancer.IntJRadiat Oncol Biol Phys(2010)vol.77(2)pp.477-83

• Adkison etal.PhaseITrialofPelvic NodalDoseEscalation With Hypofractionated IMRTforHigh-Risk Prostate Cancer.IntJRadiat Oncol Biol Phys (2012)vol.82(1)pp.184-90

Enpratique…

Moon,D.H.,Basak,R.S.&Chen,R.C.Patterns ofCareofNode-Positive Prostate CancerPatientsAcross theUnited States:ANationalCancer DataBaseAnalysis.Clinical Genitourinary Cancer (2017).doi:10.1016/j.clgc.2017.08.004

Enattenteétudesencours

Hautrisque cN1 M+

RT+HT=standard

HT=standard

PlaceRT?GETUG21Stampede

?

pN1:placedelaradiothérapie?

pN1Hormonothérapieadjuvante =standard

Messing etal.Immediate versusdeferred androgen deprivation treatment inpatientswith node-positiveprostatecancerafterradicalprostatectomyandpelvic lymphadenectomy.LancetOncol (2006)vol.7(6)pp.472-9

Peut-onguérird’uncancerdeprostatemétastatiqueganglionnairesimplementopéré?

Abdollahetal.ImpactofAdjuvantRadiotherapyonSurvivalofPatientsWithNode-PositiveProstateCancer. JClinOncol(2014)

ChirurgiepN1mortalitéspécifiqueà8ans

Quelleestl’efficacitédeChirurgie+Hormonothérapie?

Abdollahetal.ImpactofAdjuvantRadiotherapyonSurvivalofPatientsWithNode-PositiveProstateCancer. JClinOncol(2014)

ChirurgiepN1mortalitéspécifiqueà8ans

Faut-ilajouterRT?Étudesendéfaveur

• Rusthoven etal.Theimpactofdefinitive localtherapy forlymph node-positiveprostate cancer:apopulation-based study.IJROBP(2014)vol.88(5)pp.1064-73• Kaplanetal.Patterns ofcareandoutcomes ofradiotherapy forlymph node positivity after radicalprostatectomy. BJUInternational (2013)vol.111(8)pp.

1208-14

RT:PasdebénéficesipN1

SEER1995to2007577hommesdont177avecRTadjuvante

DonnéesrétrospectivesenfaveurRT

Zagars etal.Addition ofradiation therapy toandrogen ablation improves outcome forsubclinically node-positive prostatecancer.Urology (2001)vol.58(2)pp.233-9

255pts

Curagegg stoppésiextempo pN1

HT+RTvsHTseule• survieglobale10ans(67%vs46%,p =0,008)• contrôlelocal(89%vs49%,p<0,001)• surviesansméta(85%vs56%,p=0,006)

Patients pN1 : Bénéfice RT+HT adjuvante dans population sélectionnée ?

• DaPozzo, etal.Long-term follow-upofpatientswith prostatecancerandnodalmetastases treated bypelvic lymphadenectomy andradicalprostatectomy: thepositiveimpactofadjuvantradiotherapy. EurUrol 2009;55:1003–11

• Briganti etal.,Combination ofadjuvanthormonalandradiation therapy significantly prolongs survival ofpatientswith pT2-4pN+prostate cancer:results ofamatched analysis.EurUrol 2011;59:832–40

• Abdollah etal.ImpactofAdjuvantRadiotherapy onSurvival ofPatientsWith Node-Positive Prostate Cancer.JClin Oncol (2014)

RTadjuvanteourattrapage?

RTadjuvante vsRTrattrapage:Bénéficeensurviesansmétastase Sansinfluencedunbdeganglions

Tilki,D.etal. Adjuvantradiation therapy is associated with better oncological outcome compared with salvageradiationtherapy inpatientswithpN1prostate cancertreated with radicalprostatectomy. BJUInt 119, 717–723(2017).

773patients, pN1

Faut-ilsystématiquementcombinerRT+HT?

Lawtonetal.Androgen suppression plusradiation versusradiation alone forpatients with stageD1/pathologic node-positive adenocarcinoma oftheprostate:updated results based onnational prospectiverandomized trialRadiation Therapy Oncology Group 85-31.Journal ofclinical oncology (2005)vol.23(4)pp.800-7

PatientspN1postcurage

cN1etpN1:Questionsensuspens?

• Peut-onsepasserdepreuvehistologique/curageganglionnairesiRTenvisagée?

• Prostateseule ?• Prostateetairesganglionnairespelviennes ?• RTexterne?Curiethérapie?• Quelleslimitespourlesairesganglionnaires ?• Quelledosetotale ?• Augmentationdeladosesurlesadénopathiessuspectes ?• Quelleséquenced’administration?Quelleduréed’hormonothérapie?

Conclusion

Recommandations:HT=standard;RT=optionraisonnable

Mercidevotreattention!

DonnéesSEER1988-2006

Twardetal.Radiationtherapy forclinicallynode-positiveprostateadenocarcinoma is correlated with improved overall andprostatecancer-specific survival.Pract Radiat Oncol (2013)vol.3(3)pp.234-40

Surviespécifique Survieglobale

1100patientsRT=meilleuresurviespécifiqueà10ans(63%vs50%,p<0,01)

SEER1995-2005patientscN1

Rusthoven etal.Theimpactofdefinitive localtherapy forlymph node-positiveprostatecancer:apopulation-based study. IJROBP(2014)vol.88(5)pp.1064-73

869patients

DonnéesNationalCancerDataBase(NCI)

636patientssurvieà5ansdanslegroupeirradié(72%contre53%,p<0,001)

RT=+20%à5ans

Linetal.Androgen deprivation with orwithout radiationtherapy forclinicallynode-positiveprostatecancer.JNCI(2015)vol.107(7)

Métastasesganglionnairesextrapelviennes(M1a):faut-iluntraitementlocal?

Culp etal.Might MenDiagnosed withMetastatic ProstateCancerBenefit from DefinitiveTreatment ofthePrimary Tumor?ASEER-BasedStudy.European Urology (2014)