prostate cancer SD

Question 1

3 zones of the prostate

Answer 1

peripheral
transition
central

Question 2

What zone of the prostate does cancer mostly form in?

Answer 2

peripheral zone 70%

Question 3

diseases of the prostate

Answer 3

prostatitis

benign porstatic hyperplasia

prostatic carcinoma

Question 4

age of incidence of prostate diseases

Answer 4

most commonly over 60 years

Question 5

What do prostatic diseases do to the prostate?

Answer 5

cause enlargement of the prostate

Question 6

What does an enlarged prostate cause?

Answer 6

• compression of the intraprostatic portion of the urethra
• impaired urine flow
• increased risk of urinary infections

Question 7

RF for prostate cancer

Answer 7

age

genetics - FHx, 2-3x risk if first degree relative was diagnosed with PC U50yrs

race - 3x risk African/Caribbean

diet - red meat = inc risk, soya = protective

Question 8

How to diagnose prostate cancer?

Answer 8

DRE - digital rectal examination

PSA blood test

Question 9

What is DRE?

Answer 9

digital rectal examination

• feel for any prostate enlargement, irregular nodes, rigidity, masses
• normal prostate = smooth

Question 10

drawbacks of DRE

Answer 10

• males get embarassed
• mass already reached certain size to be detected by touch

Question 11

diagnosis by PSA

Answer 11

PSA is a serine protease produced by prostatic ductal epithelium

abnormal prostate - inc AR -> inc PSA

normal PSA upper limit = 3-4 ng/ml

Question 12

What can affect PSA levels?

Answer 12

prostate biopsy
DRE
ejaculation
BPH
proatatitis
intense exercise

Question 13

limitations of PSA diagnosis

Answer 13

• 20% of PC missed by having normal PSA
• 2/3 with high PSA don’t have PC
• BPH, prostatitis, urinary infections can lead to rased PSA
• some tumours grow very slowly and never progress, some rapidly and lethal
• no PSA screening in UK

Question 14

TRUS - trans rectal ultra sonography

Answer 14

follow up from +ve DRE and PSA test

ultrasound allows imaging of prostate

can take biopsy if want

highly invasive

Question 15

What grading system is used for stratifying prostate cancer?

Answer 15

Gleason Grade

Question 16

How is Gleason grade determined?

Answer 16

adding the 2 most typical grades of the cells in the tissue sample

Question 17

prostatic bone metastases

Answer 17

often present as
- localised bone pain
- back pain from vertebral metastases

osteosclerotic with areas of new bone formation

Question 18

types of Tx for PC

Answer 18

1. watchful waiting
2. surgery - radical prostatectomy
3. treatment - androgen deprivation therapy

Question 19

watchful waiting

Answer 19

some PCs don’t progress or spread

if pt has no Sx, can get no Tx and are monitored for any changes

no s/e of surgery/drugs

if situation changes, Tx can begin

Question 20

surgery

Answer 20

radical prostatectomy

major operation - blood loss, nerves surounding prostate

1. keyhole surgery by hand
2. robot assisted surgery - Da Vinci robot

Question 21

advantages of using robot assisted surgery

Answer 21

less infection, blood loss
faster healing time
less time in hospital

Question 22

Orchiectomy

Answer 22

surgical castration

Question 23

What is used for chemical castration?

Answer 23

LHRH agonists

Question 24

How to LHRH agonists work?

Answer 24

lower the amount of testosterone made by the testicles

continuous agonist presence leads to decreased levels of LHRH receptor levels on pituitary gland

** doesn’t interact with AR
** LOWERS TESTOSTERONE/DHT LEVELS

Question 25

example of LHRH agonist

Answer 25

Zoladex (goserelin)

Question 26

How does Zoldex/Goserelin work?

Answer 26

The continuous agonist presence leads to DECREASED levels of LHRH R levels on pituitary gland

Question 27

drug to inhibit AR

Answer 27

Casodex (Bicalutamide)

Question 28

MOA Casodex (Bicalutamide)

Answer 28

– Binds to AR directly
– AR STILL ENTERS THE NUCLEUS
– Casodex prevents gene transcription
- Alter dose depending upon response – PSA test
- outcompetes DHT

Question 29

resistance to Casodex (Bicalutamide)

Answer 29

• Drug Tx slows down cancer growth
• after 2-3 years the pathway can modify/mutate and no longer requires testosterone
• Cells start to grow rapidly again

Question 30

CRPC

Answer 30

• Androgen Receptor Mutation
• LBD mutation – resistance mechanism
• Allows OTHER hormones to bind to AR
• allows multiple agonists to activate AR
• Oestrogens, Progesterone, Glucocorticoids
• Antagonists can become AGONISTS
• flutamide became a strong agonist with T877A mutation
• T877A Allows conformational change of the receptor to activate genes

Question 31

relapsed PC Tx

Answer 31

Taxanes - Docetaxal

Question 32

s/e Docetaxal

Answer 32

Neutropenia
Anemia
Hair loss
Fluid retention
Diarrhea
Nausea
Rash
Mouth sores
Fingernail changes

Question 33

Tx for Castrate Resistant Disease

Answer 33

Enzalutamide

Question 34

Who is Enzalutamide reserved for?

Answer 34

patients with metastasis, CRPC disease

Question 35

Abiraterone MOA

Answer 35

• prevents testosterone biosynthesis
• inhibits CYP17 which prevents conversion of progestens to androgens
• no substrate for AR
• cause mineralocorticoid excess
• decreases cortisol - ACTH is activated
• inc mineralocorticoids
• Tx = prednisone/dexamethasone, to lower ACTH

Question 36

AR variants

Answer 36

• LBD removed, drugs can’t bind
• resistant to ADT, enzalutamide & abiraterone
• resistance to apoptosis

Question 37

Tx for CRPC

Answer 37

Abiraterone
&
Enzalutamide

Question 38

Why enzalutamise > Bicalutamide (Casodex)?

Answer 38

doesn’t become partial agonist when it mutates