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ProstateCancer
Dr.AndresWiernik2017
Objectives
YES!!!1. Epidemiology2. BiologyorNaturalHistoryofProstateCancer3. Treatment
NO!!!1. ProstateCancerScreening- controversies
Whichisthemostcommoncancerdiagnosedinmen?
1. Lung2. Prostate3. Colon4. Pancreas5. Lymphoma
What%ofnewlydiagnosedProstateCancerpatientsarealiveat5years?
1. 5%2. 25%3. 50%4. 75%5. 99%
WhichofthefollowingisNOTariskfactorforProstateCancer?
• Ageover50• African-American• FatherwithhistoryofProstateCancer• VitaminEsupplementation• Finasteride
Epidemiology
ProstateCancer2014
ProstateCancer2016
ProstateCancer2016
ProstateCancer2016
ProstateCancer2016
ProstateCancer2016
ProstateCancer2016
ProstateCancer2016
RiskFactorsforProstateCancer
• Gender• Age• Race• FamilyHistory (father,brotherorson)• Hormones• VitaminEsupplementation
• 35533menin427sitesinUSA,CanadaPuertoRico• PSAlessthan4ng/mL• 55orolder(50orolderifBlack)
• 4arms:• Selenium200ug/day• Vit E400IU/day• Vit E+Selenium• Placebo
Followedfor7-12years
p =0.008
VitaminEvs Placebo
“Dr.Wiernik– isthereanythingIcantaketopreventProstateCancer?”
GnRH
5AlphaReductase INHIBITOR
Finasteride
TheProstateCancerPreventionTrialFinasteride vs Placebo
NEJM– Aug2003
NEJM– Aug2013
Finasteride asCancerPrevention
• IdoNOTrecommendFinasteride forprostatecancerprevention
BiologyandNaturalHistoryofProstateCancer
DiagnosisofProstateCancer
• Localizeddisease(orlocallyadvanced)• 90-95%
• MetastaticDisease– StageIV• 5-10%
ProstateCancer2016
Case:ClassicClinicPatientMr.Cisa55-year-oldAfricanAmericanmalewhoyouseeinclinic
• BMI35kg/m2
• PSA2yearsagowas4ng/mL,now8 ng/mL• Asymptomatic• Comorbidities:hypertensionanddiabetes• Digitalrectalexamshows30-gramprostatewithoutnodules• APelvicMRIshowsevidenceof
• T1lesion• NoLNinvolvement
Case:Mr.C
• BiopsyResults• Gleasonscore:4+4=8/10,4of4coresintherightmid(50%)andrightbase(80%)• Staging:cT1c• PSAlevel:8
DonaldGleason
GLEASONGRADE
LocalizedProstateCancer:RiskStratification
1. Localizedvs LocallyAdvanced?2. PSAlevel?3. GleasonScore?
%Alive %Deceased
AgeatDiagnosis
YearsFollowingDiagnosisJAMA2005Albertsen,etal
Case:Mr.C
LOWRISK IntermediateRISK HIGHRISK
PSA≤10 PSA10-20 PSA>20
Gleason≤6 Gleason7 Gleason≥8
T2aorsmaller T2b T2c orgreater
LocalizedProstateCancer:RiskStratification
DetermineLifeExpectancyActiveSurveillancevs Treatment
Treatmentoptionsfor“Localized”ProstateCA
1. RadicalProstatectomy
2. XRT• ExternalBeamRT/EBRT• Brachytherapy
3. ActiveSurveillance
Case:Mr.C
PSAlevel
Time2years
• Mr.Creturnstoyourclinic– 7yearsurveillance.
• Wife:“Hehasbeencomplainingofbackpainfor4weeks”
• HisPSAis80
• BoneScansandCTC/A/Pshowevidenceofdiffusemetastaticdiseaseinthespine
• Biopsy:MetastaticProstateCancer
Case:Mr.C
Case:Mr.C
PSAlevel
Time2years 7 years
Whatisyournextstepinmanagement?
1. Lupron2. Lupron+Casodex3. Chemotherapy4. RadiationTherapy5. Zometa
ProstateCancer
• Localizeddisease(orlocallyadvanced)
• MetastaticDisease– StageIV
ProstateCancer:TreatmentMenu
ADPC– “Appetizer”:
1- SurgicalCastration$
2.MedicalCastration$$$- GnRH Agonist
- Leuprolide(Lupron)- GnRH Antagonist
- Degarelix
- Non-esteroidal Antiandrogen- Bicalutamide (Casodex) $$- Flutamide (Eulexin) $$
CRPC– “Entrée”:
1- Antiandrogens- NonsteroidalAntiandrogen $$
- Bicalutamide (Casodex)- Flutamide (Eulexin)
- Ketoconazol $- CYP17inhibitors $$$
- Abiraterone- ARAntagonists $$$
- Enzalutamide
2.Chemotherapy $$- Docetaxel- Cabazitaxel
3.Immunotherapy $$$$- Sipulecel T
4.Radium223 $$$
SideOrders:
PreventionofSRE:- Biphosphanate Therapy- Denosumab
PalliativeCare
PalliativeRadiation
Case:Mr.C
PSAlevel
Time2years 7 years
ADPCAndrogen“Dependent”
ProstateCancer
ProstateCancer:TreatmentMenu
ADPC– “Appetizer”:
1- SurgicalCastration$
2.MedicalCastration$$$- GnRH Agonist
- Leuprolide(Lupron)- GnRH Antagonist
- Degarelix
- Non-esteroidal Antiandrogen- Bicalutamide (Casodex) $$- Flutamide (Eulexin) $$
CRPC– “Entrée”:
1- Antiandrogens- NonsteroidalAntiandrogen $$
- Bicalutamide (Casodex)- Flutamide (Eulexin)
- Ketoconazol $- CYP17inhibitors $$$
- Abiraterone- ARAntagonists $$$
- Enzalutamide
2.Chemotherapy $$- Docetaxel- Cabazitaxel
3.Immunotherapy $$$$- Sipulecel T
4.Radium223 $$$
SideOrders:
PreventionofSRE:- Biphosphanate Therapy- Denosumab
PalliativeCare
PalliativeRadiation
GnRH
Case:Mr.C
PSAlevel
Time2years 7 years
Case:Mr.C
PSAlevel
Time2years 7 years 8 years
Case:Mr.C
PSAlevel
Time2years 7 years 8 years
CastrationResistantProstateCancer
Hypothesis:AndrogenDeprivationTherapy-ADT(“Castration”)
é PSA
AndrogenDeprivation
ADPCAndrogen“Dependent”
ProstateCancer
2-10years
é PSA
êPSA
CRPCCastrationResistantProstateCancer
Hypothesis:AndrogenDeprivationTherapy-ADT(“Castration”)
é PSA
AndrogenDeprivation
ADPCAndrogen“Dependent”
ProstateCancer
2-10years
é PSA
êPSA
CRPCCastrationResistantProstateCancer
HowdoesthetumorsurvivewithlowlevelsofAndrogen?
• Tumor-producedandrogensvia17-20lyase upregulation canpromotesurvival/growthwhen:• IncreasedARexpression1• GeneticalterationsinAR2• IncreasedARcofactorexpressionlevels3
• TotalARindependence• AbsenceofallARproductionandsignalingin25%ofallpost-chemotherapypts 4
CRPCCastrationResistantProstateCancer
1. ChenCD,etal.NatureMed.2004;10:33-39.2. Zaplin ME,etal.JClin Oncol.2003;21:2673-2678.3. Pienta KJ,etal.Clin CancerRes.2006;12:1665-1671.4. Tzelepi VetalClin CancerRes2012;18:666-77
Wow!!!
ProstateCancer:TreatmentMenu
ADPC– “Appetizer”:
1- SurgicalCastration$
2.MedicalCastration$$$- GnRH Agonist
- Leuprolide(Lupron)- GnRH Antagonist
- Degarelix
- Non-esteroidal Antiandrogen- Bicalutamide (Casodex) $$- Flutamide (Eulexin) $$
CRPC– “Entrée”:
1- Antiandrogens- NonsteroidalAntiandrogen $$
- Bicalutamide (Casodex)- Flutamide (Eulexin)
- Ketoconazol $- CYP17inhibitors $$$
- Abiraterone- ARAntagonists $$$
- Enzalutamide
2.Chemotherapy $$- Docetaxel- Cabazitaxel
3.Immunotherapy $$$$- Sipulecel T
4.Radium223 $$$
SideOrders:
PreventionofSRE:- Biphosphanate Therapy- Denosumab
PalliativeCare
PalliativeRadiation
NEJM,2013
Abiraterone priortoChemo
ProstateCancer:TreatmentMenu
ADPC– “Appetizer”:
1- SurgicalCastration$
2.MedicalCastration$$$- GnRH Agonist
- Leuprolide(Lupron)- GnRH Antagonist
- Degarelix
- Non-esteroidal Antiandrogen- Bicalutamide (Casodex) $$- Flutamide (Eulexin) $$
CRPC– “Entrée”:
1- Antiandrogens- NonsteroidalAntiandrogen $$
- Bicalutamide (Casodex)- Flutamide (Eulexin)
- Ketoconazol $- CYP17inhibitors $$$
- Abiraterone- ARAntagonists $$$
- Enzalutamide
2.Chemotherapy $$- Docetaxel- Cabazitaxel
3.Immunotherapy $$$$- Sipulecel T
4.Radium223 $$$
SideOrders:
PreventionofSRE:- Biphosphanate Therapy- Denosumab
PalliativeCare
PalliativeRadiation
NEJM,2014
Enzalutamide priortoChemo
ProstateCancer:TreatmentMenu
ADPC– “Appetizer”:
1- SurgicalCastration$
2.MedicalCastration$$$- GnRH Agonist
- Leuprolide(Lupron)- GnRH Antagonist
- Degarelix
- Non-esteroidal Antiandrogen- Bicalutamide (Casodex) $$- Flutamide (Eulexin) $$
CRPC– “Entrée”:
1- Antiandrogens- NonsteroidalAntiandrogen $$
- Bicalutamide (Casodex)- Flutamide (Eulexin)
- Ketoconazol $- CYP17inhibitors $$$
- Abiraterone- ARAntagonists $$$
- Enzalutamide
2.Chemotherapy $$- Docetaxel- Cabazitaxel
3.Immunotherapy $$$$- Sipulecel T
4.Radium223 $$$
SideOrders:
PreventionofSRE:- Biphosphanate Therapy- Denosumab
PalliativeCare
PalliativeRadiation
ChemotherapyinCRPC
NEJM,2004
ProstateCancer:TreatmentMenu
ADPC– “Appetizer”:
1- SurgicalCastration$
2.MedicalCastration$$
- GnRH Agonist- Leuprolide (Lupron)
$$- GnRH Antagonist
- Degarelix$$$
- Non-esteroidal Antiandrogen- Bicalutamide (Casodex)
$$- Flutamide (Eulexin)
$$
CRPC– “Entrée”:
1- Antiandrogens- Nonsteroidal Antiandrogen
$$- Bicalutamide (Casodex)- Flutamide (Eulexin)
- Ketoconazol$
- CYP17inhibitors$$$
- Abiraterone- ARAntagonists
$$$- Enzalutamide
2.Chemotherapy$$
- Docetaxel- Cabazitaxel
3.Immunotherapy$$$$
SideOrders:
PreventionofSRE:- Biphosphanate Therapy- Denosumab
PalliativeCare
PalliativeRadiation
ProstateCancer:TreatmentMenu
ADPC– “Appetizer”:
1- SurgicalCastration$
2.MedicalCastration$$$- GnRH Agonist
- Leuprolide(Lupron)- GnRH Antagonist
- Degarelix
- Non-esteroidal Antiandrogen- Bicalutamide (Casodex) $$- Flutamide (Eulexin) $$
CRPC– “Entrée”:
1- Antiandrogens- NonsteroidalAntiandrogen $$
- Bicalutamide (Casodex)- Flutamide (Eulexin)
- Ketoconazol $- CYP17inhibitors $$$
- Abiraterone- ARAntagonists $$$
- Enzalutamide
2.Chemotherapy $$- Docetaxel- Cabazitaxel
3.Immunotherapy $$$$- Sipulecel T
4.Radium223 $$$
SideOrders:
PreventionofSRE:- Biphosphanate Therapy- Denosumab
PalliativeCare
PalliativeRadiation
Sipulecel T- (PROVENGE)
Sipulecel T- (PROVENGE)
p=0.03
MedianOSimprovedby4.1months
Cost:$93000
NEJM,2014
ProstateCancer:TreatmentMenu
ADPC– “Appetizer”:
1- SurgicalCastration$
2.MedicalCastration$$$- GnRH Agonist
- Leuprolide(Lupron)- GnRH Antagonist
- Degarelix
- Non-esteroidal Antiandrogen- Bicalutamide (Casodex) $$- Flutamide (Eulexin) $$
CRPC– “Entrée”:
1- Antiandrogens- NonsteroidalAntiandrogen $$
- Bicalutamide (Casodex)- Flutamide (Eulexin)
- Ketoconazol $- CYP17inhibitors $$$
- Abiraterone- ARAntagonists $$$
- Enzalutamide
2.Chemotherapy $$- Docetaxel- Cabazitaxel
3.Immunotherapy $$$$- Sipulecel T
4.Radium223 $$$
SideOrders:
PreventionofSRE:- Biphosphanate Therapy- Denosumab
PalliativeCare
PalliativeRadiation
Radium-223
NEJM,2013
Radium-223
NEJM,2013
Radium-223
Case:Mr.C
PSAlevel
Time2years 7 years 8 years
CRPCADPC
Death
10-15years?
ASCO2014Whynottreatwith
chemotherapyupfront?
PatientswithnewlydiagnosedmetastaticProstateCancer
Docextal vs ADT
NEJM2015
NEJM2015
