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)