Prostate Cancer€¦ · 11/09/2017  · Which of the following is NOT a risk factor for Prostate...

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

ThankYou!

AndresWiernik

awiernik@gmail.com