Prostate

Question 1

What is the Gleason score?

Answer 1

A pathological score based on prostate architecture and differentiation
Gleason 2-4 low risk (well differentiated)
Gleason 5-7 intermediate
Gleason 8-10 high risk (poorly differentiated)

Question 2

What is the deal with prostate cancer screening?

Answer 2

Not recommended as population based programme due to high rates of over diagnosis and treatment

Individuals can make an informed decision regarding the benefits of PSA testing

Question 3

What are some risk factors for prostate cancer

Answer 3

Age - biggest risk factor, 99% occur in those lord then 50
Family history
BRCA (especially BRCA2 - higher Gleason and worse prognosis)
African Americans

Question 4

What is PSA and what is the normal range?

Answer 4

Protein released from prostate cells - specific to prostate but not to prostatic malignancy
Normal range 0-4 micrograms/litre

Question 5

What conditions/situations can cause a high PSA?

Answer 5

Daily variation
Prostate cancer
Urine infection
Urinary retention
DRE
Prostate massage 
Prostatitis 
BPH

Question 6

In those with an intermediate PSA (4-10) what additional test can be done to determine likelihood of malignancy?

Answer 6

PSA is mostly protein bound, even more so when there is prostate cancer, therefore the free PSA can be measured. If it is less than 10% then malignancy is more likely.

Question 7

What is recommended to diagnose prostate cancer?

Answer 7

Prostate biopsy - USS or MRI guided

At least 12 cores needed minimum

Question 8

How is prostate cancer staged?

Answer 8

TNM + Gleason score + PSA

Question 9

What is the classification of low risk prostate cancer?

Answer 9

PSA less then 10
Gleason less than 6
T1 or T2a (tumour only detected incidentally on biopsy or tumour only involving less than half a lobe of the prostate)

Need all 3 to be low risk

Question 10

What is the classification of intermediate risk prostate cancer?

Answer 10

Gleason score 7
PSA 10-20
T2b - tumour only involving one lobe of the prostate

Only need one of above to be intermediate risk

Question 11

What is the definition of high risk disease?

Answer 11

One of:
PSA greater than 20
Gleason 8-10
T2c or greater

Question 12

When is staging with bone scan/ct cap recommended?

Answer 12

Intermediate and high risk disease

Question 13

What are the options of treatment for localised disease?

Answer 13

Watchful waiting - in those not eligible for curative treatment, wait until progression occurs then start androgen deprivation treatment
Radical prostatectomy
External beam radiotherapy
Brachytherapy
Active surveillance - watching closely to identify disease progression then starting curative treatment (out of the 3 above)

Question 14

What treatments are recommended for high risk localised prostate cancer?

Answer 14

Radical prostatectomy with pelvic lymphadectomy

Or radical radiotherapy with both neo-adjuvant and adjuvant androgen deprivation therapy

Question 15

What are the main treatment options for metastatic carstrate sensitive prostate cancer?

Answer 15

Androgen deprivation therapy

If able to tolerate - 6 cycles of docetaxel chemotherapy with prednisone pre-med

Question 16

What is androgen deprivation therapy?

Answer 16

Surgical orchidectomy - quick decrease in testosterone
Medical orchidectomy - use GnRH agonists which bind to receptors on the pituitary causing an initial surge in LH and testosterone but then due to constant stimulation leads to down regulation of receptors and low levels of androgens and testosterone

Question 17

What is “tumour flare” in regards to the treatment of prostate cancer? How is it prevented?

Answer 17

With the initial surge of LH and testosterone get an increase in disease and bone pain over the first few weeks (takes 3-4 weeks to reach castrate levels).
Minimise this by using a anti-androgen (bicalutimide) which blocks the androgen receptor, pre and for a period post commencement of GnRH inhibition

Question 18

What are some side effects of ADT?

Answer 18

Loss of libido
Loss of muscle mass
Increased body fat
Gynecomastia
Mood changes
Hot flashes

Question 19

What indicates development of castrate resistant metastatic disease?

Answer 19

Rising PSA
New metastases
Or increase in growth of existing metastases

Question 20

What should you do if there is the development of castrate resistance?

Answer 20

First stop the anti-androgen if the patient is on it (anti-androgens can develop agonist activity at the androgen receptor causing rise in PSA and disease progression)
Continue GnRH agonism
Look at starting other treatments

Question 21

What are some treatment options for castrate resistance prostate cancer?

Answer 21

Abiraterone
Enzalutamide
Docetaxel with ongoing prednisone
Radium -223
Carbazitaxsel

Unsure what order of treatment is preferred - nil evidence yet

Question 22

What is abiraterone and what is a main caution with its use?

Answer 22

Androgen synthesis inhibitor
Blocks the 2 enzymes that are products of the CYP 17 gene (17,20 lyase and 17 alpha hydroxylase) which stops synthesis of testosterone and androgens

Main caution is development of mineralcorticoid excess as cortisol production is decreased leading to increased ACTH and mineralcorticoid secretion (hypertension, hypokalaemia and fluid retention) This is why it is always given with glucocorticoid

Question 23

What is enzalutamide?

Answer 23

Androgen receptor blocker that works in multiple locations (ie receptor, nucleus and prevents integration of receptor into cell)
Has no risk of agonist effects unlike first generation androgen receptor blockers (bicalutamide and flutamide)

Question 24

What is radium-223 and what are its uses?

Answer 24

Radio-labelled radium gets up taken by calcimimetic cells and then emits alpha radiation to target bone mets with minimal toxicity
Good bone targeted therapy