Prostate cancer SD

Question 1

where is the location of the prostate gland?

Answer 1

The prostate gland surrounds the neck of the
bladder and urethra, weighs about 20g and is
enclosed in a fibrous capsule

Question 2

what are the 3 zones of the prostate gland?

Answer 2

*The peripheral zone accounts for 70%
*The transition zone 5%
*The central zone 25%.

Question 3

what zone in the prostate generally enlarges with age?

Answer 3

The transition zone gradually enlarges with
age

Question 4

what zone of the prostate gland does cancer mostly arise from?

Answer 4

peripheral zone

Question 5

what is the prostates function?

Answer 5

part of the male reproductive system
*Major role in seminal fluid production

Question 6

what surrounds the prostate?

Answer 6

fibro-muscular stroma
–Muscular contraction during ejaculation
This contains a thick sheet of connective tissue and a layer of smooth muscle surrounding the entire prostate gland.

Question 7

where does testosterone bind on the androgen receptor?

Answer 7

in the ligand binding domain

Question 8

what does 5ar convert testosterone to?

Answer 8

diHydro testosterone

Question 9

what does most prostatic diseases cause and result in?

Answer 9

cause enlargement of the prostate,
–Compression of the intraprostatic portion of the urethra
–Impaired urine flow
–Increased risk of urinary infections
–Acute retention of urine requiring urgent relief by catheterisation.

Question 10

what are the 3 major prostate pathologies?

Answer 10

prostatitis, BPH, prostatic carcinoma

Question 11

how does genetics increase your chances of developing prostate cancer?

Answer 11

A family history of the disease is relevant: 2-3 fold risk if a first-degree relative was diagnosed with PCa under 50 years of age.

Question 12

what race are most at risk of prostate cancer?

Answer 12

3 fold risk for African or Caribbean men compared to caucasian; the risk in
China and Japan is lower.

Question 13

how do you diagnoise prostate cancer?

Answer 13

digital rectal examination

Question 14

what are advantages and disadvantages oof DRE?

Answer 14

Immediate, very quick, cheap test, once a mass is identified additional tests can occur
Downside - Mass has already reached certain size to be detected by touch

Question 15

what is PSA?

Answer 15

Prostate Specific Antigen (PSA)
Blood Test
PSA is a 34 kDa serine protease (KLK3 gene) primarily produced by the prostatic ductal epithelium – AR REGULATED GENE

Question 16

what would an abnormal PSA show?

Answer 16

Abnormal prostate - Increased AR = increased PSA

Question 17

what can PSA levels be affected by?

Answer 17

Prostate Biopsy, DRE, Ejaculation, BPH, Prostatitis, intense exercise

Question 18

how is PSA measured? what are the limits?

Answer 18

Measured in serum which usually has an upper limit set at 3-4 ng/ml for
normal serum PSA.

Question 19

what is the main purpose of PSA?

Answer 19

We use PSA to monitor effectiveness of treatment – “is the drug working?”

Question 20

what are the limitations of PSA?

Answer 20

20% of patients missed
PSA levels could be raised by BPH or urinary tract infection

Question 21

what is TRUS?

Answer 21

Trans Rectal Ultra Sonography (TRUS) / Biopsy
Follow up from positive DRE and PSA test
*Ultrasound allows imaging of prostate

Question 22

what is the gleason grade?

Answer 22

For stratifying prostate cancer
the most common grade of the cells in a tissue sample may
be grade 3 cells, followed by grade 4 cells.

Question 23

what does prostatic bone metastases often present as?

Answer 23

as localised
bone pain, back pain from vertebral
metastases being a common initial
manifestation of the tumour.

Question 24

when may some patients decide to do waitful watching?

Answer 24

where some cancer do not progress/ spread- they have been growing very slowly
willl be monitored closely for changes
if the situation changes then treatment can begin

Question 25

what are the ways of removing the prostate?

Answer 25

Keyhole surgery by hand – surgeon makes five or six small incisions and
removes the prostate using a thin, lighted tube with a small camera on the
tip and special surgical tools
*Robot-assisted surgery – surgeon uses three robotic arms (one for the
camera and two for the surgical tools) to do the operation. The ‘Da Vinci®
Robot’.

Question 26

how is prostate surgery done by the da vinci robot?

Answer 26

Complex blood vessels and nerves surround the prostate
*Less infection, blood loss, faster healing, Less time in hospital
*Freeman and Sunderland Royal both now have these systems

Question 27

what is androgen deprivation therapy?

Answer 27

LHRH agonists (Chemical Castration)
Luteinizing hormone-releasing hormone
(LHRH) agonists are drugs that lower the
amount of testosterone made by the
testicles.
*E.g. Zoladex

Question 28

how does zoladex work?

Answer 28

Goserelin is a synthetic decapeptide hormone analogue of LHRH.
–The continuous agonist presence leads to DECREASED levels of LHRH
Receptor levels on pituitary gland

Question 29

how does casodex work?

Answer 29

Potent AR inhibition
*Leads to tumour shrinkage
Binds AR directly
–AR STILL ENTERS THE NUCLEUS
–Casodex prevents gene transcription

Question 30

what does casodex lower?

Answer 30

Does NOT lower testosterone levels – blocks AR

Question 31

what are prostate cancer cells driven by?

Answer 31

androgens

Question 32

what is a resistance mechanism or CRCP?

Answer 32

Ligand Binding Domain mutation – resistance mechanism

Question 33

what does the ligand binding domain mutation allow?

Answer 33

Allows OTHER hormones to bind to AR: allows multiple agonists to activate
AR
–Oestrogens, Progesterone, Glucocorticoids
–Antagonists can become AGONISTS…. E.g. 1st gen anti-androgen
flutamide became a strong agonist with T877A mutation
–T877A Allows conformational change of the receptor to activate genes

Question 34

what is taxanes/ docetaxal used for?

Answer 34

commonly used for
men with advanced prostate cancer.

Question 35

after relapse what can cells becoeme resistant to?

Answer 35

bicalutamide

Question 36

when is enzalutamide reserved for?

Answer 36

patients with metastasis, CRPC disease

Question 37

how does enzalutamide work?

Answer 37

enzalutamide inhibits AR- testosterone binding with higher affinity than bicalutamide
this inhibition blocks the change induced by AR-testosterone binding
it inhibits AR-testosterone nuclear transloactionand DNA transcription
it lacks partial AR agonist activity that occurs with bicalutamide resistance

Question 38

what does Abiraterone do?

Answer 38

it prevents testosterone biosynthesis

Question 39

what is the MOA of abiraterone?

Answer 39

inhibits CYP17 (effects 17-
hydroxylase/lyase activity) which
prevent conversion of progestens to
androgens = No substrate for AR
Decreases cortisol ACTH is activated
Increased mineralocorticoids
Treat with prednisone/dexamethasone
to lower ACTH

Question 40

what are AR variants resistant to?

Answer 40

Resistant to ADT, Enzalutamide & Abiraterone

Question 41

what do AR variants lead to?

Answer 41

Lead to enhanced migratory capacity,
invasiveness, elevated resistance to apoptosis

Question 42

how do AR variants work?

Answer 42

Works Independent of testosterone (No LBD)