Prostate Cancer

Question 1

What is the most common cancer in males, in the UK?

Answer 1

Prostate cancer

Question 2

Which cancer is the most common cause of death in males in the UK?

Answer 2

Lung cancer (closely followed by prostate cancer)

Question 3

Which pathway is mainly disrupted in most prostate cancers?

Answer 3

Androgen signalling pathway

Question 4

Name a TSG implicated in prostate cancer and explain how this is thought to cause prostate cancer

Answer 4

PTEN is a TSG. Loss of this facilitates antiapoptotic pathways, and may have a direct impact on androgen independent activation of the androgen receptor

Question 5

What effect does PTEN normally have on androgen signalling?

Answer 5

Antagonises it

Question 6

Which other gene has been implicated in prostate cancer?

Answer 6

BRCA2

Question 7

What is the normal function of the prostate?

Answer 7

Contributes towards the seminal fluid

Question 8

What is the main symptom of prostatic hyperplasia?

Answer 8

Problems with urination

Question 9

List two rarer symptoms of prostate cancer

Answer 9

Lower back pain

Blood in urine

Question 10

List some common sites of metastasis

Answer 10

Seminal vesicles
Bladder
Lymph nodes
Bone

Question 11

What is the main symptom of prostatic metastatic disease?

Answer 11

Bone pain

Question 12

What normally prevents PSA from being released into the blood?

Answer 12

Epithelial gap junctions
Basal cell layer
Basement membrane

Question 13

What is the cut off concentration for PSA as indicative of possible prostatic disease?

Answer 13

4ng/ml serum PSA

Question 14

List some causes of raised PSA besides BPH and malignant prostatic cancer

Answer 14

Prostatitis
UTIs
Mechanical damage (incl biopsy)

Question 15

What is done if the PSA is high?

Answer 15

Biopsy

MRI scan

Question 16

What is the problem with needle biopsies?

Answer 16

They can under or overestimate the tumour grade

Question 17

What can be done to improve accuracy of the tumour grade?

Answer 17

Repeat biopsies

Extended sampling techniques

Question 18

Which scoring system is used in prostate cancer and what does it assess?

Answer 18

Gleason scoring - assesses Grade (differentiation)

Question 19

What is the downside of biopsies and this scoring system?

Answer 19

Not useful for predicting prognosis

Question 20

What new methods are being developed to detect prostate cancer?

Answer 20

Proteomics

Nuclear magnetic resonance

Question 21

What is the best treatment for older patients with low grade tumours, and why?

Answer 21

Watchful waiting - due to the possibility of the tumour remaining latent for the patient’s lifespan (and therefore to reduce harm).

Question 22

List five other treatment options

Answer 22

Radical prostatectomy 
External beam therapy 
Brachytherapy 
Hormone therapy (LHRH analogues)
Hormone therapy (Anti-androgens)

Question 23

When is radical prostatectomy most effective?

Answer 23

For tumours confined to the prostate

Question 24

What are the main side effects of radical prostatectomy?

Answer 24

Impotence

Incontinence

Question 25

What is the criteria for operability for radical prostatectomy (PSA and age)?

Answer 25

PSA levels <10-12ng/ml

<70 years of age

Question 26

When is external beam therapy used, as opposed to brachytherapy?

Answer 26

External beam therapy - used if cancer has spread outside of prostate but HAS NOT AFFECTED OTHER ORGANS
Brachytherapy - used if tumour is contained in the prostate

Question 27

What is brachytherapy?

Answer 27

Radioactive seeds, implanted in prostate

Question 28

What is used in conjunction with external beam radiotherapy and why?

Answer 28

Computer planning - to limit toxicity to the bowel and bladder

Question 29

What are the main side effects of radiotherapy?

Answer 29

Incontinence

Sexual dysfunction

Question 30

When would hormone therapy be indicated?

Answer 30

If the cancer has metastasised to other organs

Question 31

Hormone therapy involves bilateral orchidectomy. What form does this take?

Answer 31

Chemical not surgical

LHRH agonists

Question 32

What is the rationale behind using LHRH agonists?

Answer 32

Overstimulates the pituitary, causing desensitisation and downregulation of LHRH receptors, which in turn reduces LH and testosterone production

Question 33

Name an LHRH agonist

Answer 33

Leuprolide

Question 34

What else must be given in combination with LHRH agonists and why?

Answer 34

Anti-androgens, as weak androgens are still produced by the adrenals and can stimulate the prostate via the androgen receptor.

Question 35

How do antiandrogens work?

Answer 35

May actively repress androgen target sites

Inhibit androgen receptors on prostate

Question 36

What are the main side effects of hormone therapy?

Answer 36

Osteoporosis
Memory loss
Anaemia 
Loss of libido 
Muscle atrophy 
Gynaecomastia

Question 37

When do biochemical and symptomatic signs of prostate cancer androgen independence occur?

Answer 37

Biochemical evidence of relapse - within 13 months
Symptomatic relapse - within 2 years

(since starting hormone therapy)

Question 38

What happens to the androgen receptor in androgen independent prostate cancer?

Answer 38

The androgen receptor is actually overexpressed

Question 39

Describe the androgen receptor

Answer 39

Ligand (androgen) activated transcription factor

Question 40

What causes the increased expression of androgen receptors?

Answer 40

Overexpression of genes

Gene amplification

Question 41

What causes the continued growth of the cancer despite low levels of androgens?

Answer 41

The receptor is activated in response to:
Even low levels of androgen
Co-activators
Other ligands e.g oestrogens and antiandrogens!

OR the androgen receptor pathway could be bypassed altogether by loss of PTEN function