Prostate cancer

Question 1

What is the evidence for screening?

Answer 1

ERSPC trial - 21% relative reduction in cancer mortality

PLCO trial - no prostate cancer mortality reduction. Control arm contaminated

Question 2

What are the current recommendations for screening?

Answer 2

Men should discuss with their doctor for individualised discussions

Question 3

How does testosterone interact with prostate cancer?

Answer 3

Acts as transcription factor to drive growth

Question 4

What is castration-resistant disease?

Answer 4

Progression of Ca despite castrate testosterone <1.7mmol/L

Question 5

How is castration-resistant disease diagnosed?

Answer 5

Progression of disease on androgen deprivation theraepy (ADT)

Question 6

What is the mainstay of treatment?

Answer 6

Androgen deprivation therapy

Question 7

What are the options for ADT?

Answer 7

GnRH agonists (goserelin)

GnRH antagonists (degarelix)

Bilateral oorchidectomy

Question 8

What are the benefits/cons for GnRH antagonists over agonists?

Answer 8

Benefits More rapid reduction in serum testosterone and avoiding clinical flare phenomenon

Cons: More local site reactions, monthly administration

Question 9

What is clinical flare phenomenon?

Answer 9

Initial GnRH agonism leads to transient increase in testosterone - transient flare in disease > pain, urinary retention, and spinal cord compression

Question 10

What are some options for met. castrate-resistant disease?

Answer 10

Chemo: Docetaxel/cabazitaxel

Androgen receptor targeted therapies: Abiraterone, enzalutamide

Question 11

What can you add to ADT in castrate-sensitive disease?

Answer 11

Docetaxel chemo 6 cycles
Abiraterone
Enzalutamide
Apalutamide
Local radiotherapy

Question 12

What are poor prognostic factors?

Answer 12

De novo met disaese

High volume mets

Question 13

What are the radiophaemaceuticals?

Answer 13

radium-223

Question 14

What are the immunotherapy options?

Answer 14

Sipuleucel-T

Question 15

What is the mechanism of the chemo options?

Answer 15

Stabilises microtubules during mitosis/interphase > cell death

Question 16

What is the side effect of docetaxel?

Answer 16

Sensory/motor peripheral neuropathies
Cytopenias
Hypersensitivity reactions

Question 17

What are the side effects of cabazitaxel?

Answer 17

Diarrhoea, cytopenias, sensory/motor PN (less common cf docetaxel)

Question 18

What is hte mechanism of action of abiraterone?

Answer 18

Inhibit adrenal enzymes (17alpha hydroxylase, c17, 20-lyase) that produce testosterone

Question 19

What are the common SE of abiraterone? How is it prevented?

Answer 19

Mineralocorticoid excess: HTN, hypokalaemia, peripheral oedema

Transaminitis

Concurrent glucocorticoids

Question 20

How was enzalutamide work

Answer 20

Androgen receptor antagonist

Inhibits binding of ligands to receptor and migration within cell

Question 21

What are SE of enzalutamide?

Answer 21

Fatigue ++
Cognitive decline
Falls
Seizures (rare)

Question 22

When are androgen receptor therapies indicated in Aus?

Answer 22

Post docetaxel (unless not tolerated)

Question 23

What are future directions of treatment?

Answer 23

PARP inhibition - DNA repair mechanism

Question 24

What is the prostate specific membrane antigen?

Answer 24

Very specific tumour marker

• Can be labelled with gallium for diagnosis
• Also therapeutic option if radioactive molecule addedd (lutetium)