Prostate cancer Flashcards
What is the evidence for screening?
ERSPC trial - 21% relative reduction in cancer mortality
PLCO trial - no prostate cancer mortality reduction. Control arm contaminated
What are the current recommendations for screening?
Men should discuss with their doctor for individualised discussions
How does testosterone interact with prostate cancer?
Acts as transcription factor to drive growth
What is castration-resistant disease?
Progression of Ca despite castrate testosterone <1.7mmol/L
How is castration-resistant disease diagnosed?
Progression of disease on androgen deprivation theraepy (ADT)
What is the mainstay of treatment?
Androgen deprivation therapy
What are the options for ADT?
GnRH agonists (goserelin)
GnRH antagonists (degarelix)
Bilateral oorchidectomy
What are the benefits/cons for GnRH antagonists over agonists?
Benefits More rapid reduction in serum testosterone and avoiding clinical flare phenomenon
Cons: More local site reactions, monthly administration
What is clinical flare phenomenon?
Initial GnRH agonism leads to transient increase in testosterone - transient flare in disease > pain, urinary retention, and spinal cord compression
What are some options for met. castrate-resistant disease?
Chemo: Docetaxel/cabazitaxel
Androgen receptor targeted therapies: Abiraterone, enzalutamide
What can you add to ADT in castrate-sensitive disease?
Docetaxel chemo 6 cycles Abiraterone Enzalutamide Apalutamide Local radiotherapy
What are poor prognostic factors?
De novo met disaese
High volume mets
What are the radiophaemaceuticals?
radium-223
What are the immunotherapy options?
Sipuleucel-T
What is the mechanism of the chemo options?
Stabilises microtubules during mitosis/interphase > cell death
What is the side effect of docetaxel?
Sensory/motor peripheral neuropathies
Cytopenias
Hypersensitivity reactions
What are the side effects of cabazitaxel?
Diarrhoea, cytopenias, sensory/motor PN (less common cf docetaxel)
What is hte mechanism of action of abiraterone?
Inhibit adrenal enzymes (17alpha hydroxylase, c17, 20-lyase) that produce testosterone
What are the common SE of abiraterone? How is it prevented?
Mineralocorticoid excess: HTN, hypokalaemia, peripheral oedema
Transaminitis
Concurrent glucocorticoids
How was enzalutamide work
Androgen receptor antagonist
Inhibits binding of ligands to receptor and migration within cell
What are SE of enzalutamide?
Fatigue ++
Cognitive decline
Falls
Seizures (rare)
When are androgen receptor therapies indicated in Aus?
Post docetaxel (unless not tolerated)
What are future directions of treatment?
PARP inhibition - DNA repair mechanism
What is the prostate specific membrane antigen?
Very specific tumour marker
- Can be labelled with gallium for diagnosis
- Also therapeutic option if radioactive molecule addedd (lutetium)
