Prostatacancer Hvad nyt sker der. Referat fra EAU Milano d. 15-19 Prostatacancer Hvad nyt sker der? Referat fra EAU Milano d. 15-19. marts 2013 Overlæge Johan Poulsen Urologisk Afdeling, Aalborg Sygehus King’s College Hospital, London

Prostatacancer Screening Diagnostik Intenderet kurativ behandling Symptomatisk behandling ved hormonfølsom dissemineret prostatacancer Behandling med CRPC

Diagnostik af prostatacancer PSA TRUSP + B Multiparametrisk MR-skanning + targeted biopsier

Intenderet kurativ behandling Lokaliseret PC: lavrisiko sygdom intermediær risiko højrisiko

Behandling for prostatacancer Watchful waiting, active surveillance Operativ behandling Strålebehandling Brachy terapi

Operativ behandling for PC Åben prostatektomi Robotassisteret laparoskopisk prostatektomi smerter, blødning, rekonvalescens potens radikalitet operationsresultat afhænger af, hvor syg patienten er (hvilke type indgreb det er forsvarligt at udføre) flere T3ere/T4ere opereres, også med dissimineret sygdom

Strålebehandling versus operation for PC 45.000 svenske mænd behandlet for PC. Endpoint: Mortalitet pga. PC: Dødelighed x 2 ved strålebehandling lav risiko intermediær risiko høj risiko Dødelighed x 1,7 ved strålebehandling høj-høj risiko (PSA>50) Kilde: Peter Wirklund, Karolinska i Stockholm

Endogenreceptor antagonister Medicinsk/kirurgisk kastration Bicalutamid LHRA agonister (Eligaard) LHRA antagonister (Degarelix) Evt. behandling – bisphosphonater eller Denosumab

Behandling af CRPC Doxacetel Cabazilaxel Abariterone Zoledronsyre Denosumab MDV 3100 (enzalutamid) Provenge (lipoleucel) Prostvac - VF Radium 223

Castration resistant PC The present Chemotherapy Hormone therapy Zolodronic acid Denusomab The future New hormonal agents Immunotherapy Targeted therapy New combinations

Doxacetel (taxotere)

EAU Guidelines 2011 Symptomatic patient should be offered Docetaxel chemotherapy 75 mg/m2 three weekly in combination with 2x5mg Prednisolon (Grade B recommendation)

EAU Guidelines 2011 Asymptomatic patient can be offered chemotherapy if PSA DT is low (< 3 months) imaging shows progression of measurable lesions the patients want treatment

Docetaxel monotherapy Tax 327: Overall survival Berthold DR et al. J Clin Oncol 2008;26:242-245

Cabazitaxel

Second line chemotherapy

Abiraterone Kan gives efter kemoterapi med Doxacetel Abiraterone Kan gives efter kemoterapi med Doxacetel. Kan også gives før kemoterapi

Second line ”hormone therapy

COU-AA-301: Abiraterone Acetate Overall survival

Denosumab vs Zoledronsyre

Targeting angiogenesis: Targeting Clusterin: Bone targeting: CRPC Pipeline Hormone therapy: Abiraterone MDV3100 (enzalutamid) Cytotoxics: Cabazitaxel Epothilones Targeting angiogenesis: VEGF-Trap Lenalidomide Targeting Clusterin: OGX-011 Bone targeting: RANK-L (Denosumab) Cabazantinib Src (Dasatinib, AZD0350) Alpharadin Immune system: Sipuleucel-T Prostvac Ipilimumab

Sipuleucel-T (Provenge)

IMPACT Overall Survival: Primary Endpoint Intent-to-Treat Population

Enzalutamid (MDV3100)

Alpharadin (Radium-223)

Screening for prostatacancer kommer! Screening for prostatacancer (ESPC undersøgelse – 300.000 europæiske mænd) 308 patienter skal have taget PSA 9 diagnoser af prostacancer skal stilles 1 prostatacancer patient redder livet Screening for prostatacancer kommer!

Docetaxel first line standard Abiraterone second line standard Take home messages Docetaxel first line standard Abiraterone second line standard Cabazitaxel third line standard Abiraterone will replace Docetaxel Cou 302 Sequenz: AA – DOC – CAB Denusomab complements ZOL More new compounds to come

King’s College Hospital, London