Prostate Cancer

Question 1

which staging system is used for prostate cancer?

Answer 1

Gleason

Question 2

what is PSA?

Answer 2

Prostate Specific Antigen

– a kallikrein protein secreted by the epithelial cells of the prostate into the urethral duct.

Question 3

where is PSA physiologically found normally? where is it abnormal to find?

Answer 3

normal to be found in urine

but not normal in the blood (has bypassed the basement membrane)

Question 4

what levels of PSA in the blood indicates possible prostate cancer?

what else can increase PSA levels apart from prostatic cancer?

Answer 4

over 4ng/ml

can rise to >2000 nm/ml in aggressive metastatic disease

but other disease like inflammation can lead to increased PSA levels

Question 5

what effect can prostatic hyperplasia have on urination?

Answer 5

restricted

Question 6

what does the prostate depend on for growth?

Answer 6

testosterone (from testes)

Question 7

what is the inheritance pattern of prostate cancer?

Answer 7

prostate cancers are heterogeneous
– due to both defects on proto-oncogenes and TSGs

PTEN and BRCA2 are potential TSGs involved.

• However, there is no specific TSG or oncogene that predisposes or causes prostate cancer.

Closest relationship is with androgen-signalling pathways
– “androgen-independent” PC is very aggressive.

Question 8

which type of PC is most aggressive?

Answer 8

androgen independent prostate cancer

becomes incurable and death follows within 7 months

Question 9

epidemiology of PC

Answer 9

most common western male cancer
– incidence increases with age.

most common in the UK for males

Question 10

which TSGs are possibly involved in PC?

Answer 10

PTEN and BRCA2

Question 11

how is PC graded?

Answer 11

Gleason grading system
– two largest areas of tumour are biopsied and scored 1-5
(1 = least aggressive)

the two scores are quoted plus their sum
– e.g. 3 + 3, 6.

2-4 = low grade
5-7 = intermediate grade
8-10 = high grade.

Question 12

what drugs are used as part of PC treatment?

Answer 12

1) Leuprolide
– LHRH super-agonist
– analogue to GnRH and agonises LH release

2) Flutamide
– a steroidal anti-androgen
– blocks the testosterone receptor on the prostate gland.

Question 13

what effect can leuprolide, a LHRH agonist, have on testerone release?

Answer 13

this agonises LH release so much that it causes GnRH receptor down-regulation in the adenohypophysis

–>so less LH is released so less testosterone is released

Question 14

what are the 2 methods of treating PC?

Answer 14

drugs (anti-androgenic) and surgery

Question 15

what are the surgical options for prostate cancer (non metastatic)?

Answer 15

1) Radical prostatectomy
– when the cancer is confined to the prostate gland.

2) External beam radiotherapy and brachytherapy
(small radioactive “seeds” implanted).

Question 16

why may a 75 year old man receive hormone therapy rather than surgery for PC?

Answer 16

risks involved with anaesthesia

Question 17

what is the logic behind giving leuprolide and flutamide as a combination ?

Answer 17

leuprolide will decrease testosterone production

flutamide will reduce testosterone uptake by the cancerous prostate gland by blocking the receptor

Question 18

what mechanisms contribute to the recurrence of PC despite anti-androgenic treatment?

Answer 18

1) increased receptor sensitivity
2) decreased co-receptor expression in internal signalling pathways
3) mutation of testosterone receptor on prostate so can be activated

Question 19

how can markers of aggressive vs latent prostate cancer be detected?

Answer 19

a. Proteomics.
b. NMR.
c. cDNA microarrays
– detect unique patterns of gene expression
– e.g. EZH2 gene.

Question 20

what are the issues with PSA testing being done above a certain age?

Answer 20

• unnecessary stress
• extra invasive tests
• PSA testing is sensitive but not very specific

Question 21

why is the PSA test not very specific?

Answer 21

there is no great link between PSA marker and disease

PSA can be raised due to:

• prostatitis or UTIs (older people are more likely to pick up UTIs)
• surgery/catherisation
• cycling/trauma
• PSA increases with age

Question 22

why does prostate cancer become androgen-INdependent?

Answer 22

the cancerous prostate being an androgen-dependent gland is given anti-androgenic treatment (inhibiting androgens) so the prostate becomes androgen independent after a few years

Question 23

how common is prostate cancer? [deaths]

Answer 23

2nd most common cause of male cancer death

lung cancer is the most common cause of death due to cancer

Question 24

what are the risk factors of prostate cancer?

Answer 24

• age (biggest)
• afro-carribean
• family history
• dietary factors (high fat, meat,alcohol)
• occupational exposure to cadmium

Question 25

how does prostate cancer often present?

Answer 25

asymptotically

Question 26

how does lower urinary tract obstruction present?

Answer 26

- hesitancy - poor stream - terminal dribbling - nocturia - pain when urinating

Question 27

what are the signs of metastatic spread?

Answer 27

- bone pain (severe in malignancy) - cord compression - systemic: malaise anorexia, weight loss - paraneoplastic syndromes e.g. hypercalcaemia

Question 28

how can PSA be increased without cancer?

Answer 28

- prostatitis or UTIs (older people are more likely to pick up UTIs) - surgery/catherisation - cycling/trauma - PSA increases with age

Question 29

what is CT/MRI used for?

Answer 29

assess extent of local invasion and lymph node involvement done in conjunction with biopsy used for Gleason scoring invasive biopsy is best avoided so multi-parameter MRI is used

Question 30

what is the low risk Gleason score?

Answer 30

2-4

Question 31

how is prostate cancer managed?

Answer 31

- active observation of low grade tumours in older people - radical prostatectomy (benign tumour) - external beam radiotherapy (outside prostatic capsule)

Question 32

what are the side effects of prostatectomy?

Answer 32

incontinency and impotence due to proximity of nerves to prostate

Question 33

what group of people would prostatectomy be the most successful? criteria for operability

Answer 33

< age of 70 | PSA < 10-12 ng/ml

Question 34

when is external beam radiotherapy used instead of prostatectomy?

Answer 34

prostatectomy is used when tumour is confined to prostate radiotherapy is used for tumour that has spread outside the prostate capsule (but other organs have not been affected)

Question 35

what are the side effects of radiotherapy?

Answer 35

impotency and incontinence toxicity to bladder and bowel limited by computer planning

Question 36

what are the side effects of using LHRH agonists?

Answer 36

due to anti-androgenic effects: - osteoporosis - loss of libido - anaemia - muscle atrophy - memory loss - gynaecomastia

Question 37

what is the source of WEAK androgens?

Answer 37

adrenals | e.g. androstenedione

Question 38

what role may PTEN deactivation have in prostate cancer?

Answer 38

1) anti-apoptotic (PTEN ensures apoptosis occurs) | 2) no antagonism of androgen signalling (PTEN is an antagonist)

Question 39

what are the clinical features of prostate cancer?

Answer 39

- difficulty urinating | - rarer: haematuria, lower back pain

Question 40

what kind of gland is the prostate?

Answer 40

exocrine (make use of ducts)

Question 41

what does the PSA test not distinguish between?

Answer 41

metastatic cancer and benign prostatic hyperplasia both affect the basal cell layer, epithelial layer and basement membrane

Question 42

when is Gleason scoring done?

Answer 42

after a positive PSA and digital rectal exam

Question 43

why is biopsy a poor form for diagnosis?

Answer 43

- can underestimate or overestimate the tumour grade - needs repeat biopsies (very invasive) - not useful for predicting prognosis

Question 44

what is a strong argument AGAINST routine PSA screening in men without symptoms?

Answer 44

- a raised PSA means further invasive tests need to be done - unnecessary anxiety till results - detected malignancy needs treatment with unpleasant side effects that reduce quality of life - possibility the lesion if left alone has no problems for the man during his lifetime

Question 45

when is hormone therapy used?

Answer 45

metastatic prostate cancer

Question 46

what does hormone therapy involved?

Answer 46

- orchidectomy (remove main source of testosterone) | - LHHR analogue

Question 47

HPG axis

Answer 47

- LHRH (hypothalamus) - LHRH receptor (pituitary) - LH (released) - Leydig (LH binds) - testosterone

Question 48

what effect does LHRH agonist have?

Answer 48

overstimulates LHRH receptor on pituitary causing it to desensitise stops LH and testosterone production

Question 49

why are anti-androgens used alongside LHRH agonists?

Answer 49

weak androgens still produced by adrenals

Question 50

describe the relapse after hormone therapy

Answer 50

- 13 months later there is a biochemical relapse - 2 years later there is a symptomatic relapse - androgen independence creates a very aggressive cancer - death within 7 months

Question 51

how does the cancer respond to low circulating androgens to become "androgen independent"?

Answer 51

- amplifies response to low residual levels of androgens or weak androgens - increased levels of androgen receptors - increase proteins required for androgen signalling e.g co-activators - decreased co-repressors - mutation of androgen receptor so other ligands can activate it