prostate cancer SD Flashcards

1
Q

3 zones of the prostate

A

peripheral
transition
central

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2
Q

What zone of the prostate does cancer mostly form in?

A

peripheral zone 70%

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3
Q

diseases of the prostate

A

prostatitis

benign porstatic hyperplasia

prostatic carcinoma

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4
Q

age of incidence of prostate diseases

A

most commonly over 60 years

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5
Q

What do prostatic diseases do to the prostate?

A

cause enlargement of the prostate

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6
Q

What does an enlarged prostate cause?

A
  • compression of the intraprostatic portion of the urethra
  • impaired urine flow
  • increased risk of urinary infections
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7
Q

RF for prostate cancer

A

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

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8
Q

How to diagnose prostate cancer?

A

DRE - digital rectal examination

PSA blood test

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9
Q

What is DRE?

A

digital rectal examination

  • feel for any prostate enlargement, irregular nodes, rigidity, masses
  • normal prostate = smooth
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10
Q

drawbacks of DRE

A
  • males get embarassed
  • mass already reached certain size to be detected by touch
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11
Q

diagnosis by PSA

A

PSA is a serine protease produced by prostatic ductal epithelium

abnormal prostate - inc AR -> inc PSA

normal PSA upper limit = 3-4 ng/ml

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12
Q

What can affect PSA levels?

A

prostate biopsy
DRE
ejaculation
BPH
proatatitis
intense exercise

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13
Q

limitations of PSA diagnosis

A
  • 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
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14
Q

TRUS - trans rectal ultra sonography

A

follow up from +ve DRE and PSA test

ultrasound allows imaging of prostate

can take biopsy if want

highly invasive

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15
Q

What grading system is used for stratifying prostate cancer?

A

Gleason Grade

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16
Q

How is Gleason grade determined?

A

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

17
Q

prostatic bone metastases

A

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

osteosclerotic with areas of new bone formation

18
Q

types of Tx for PC

A
  1. watchful waiting
  2. surgery - radical prostatectomy
  3. treatment - androgen deprivation therapy
19
Q

watchful waiting

A

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

20
Q

surgery

A

radical prostatectomy

major operation - blood loss, nerves surounding prostate

  1. keyhole surgery by hand
  2. robot assisted surgery - Da Vinci robot
21
Q

advantages of using robot assisted surgery

A

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

22
Q

Orchiectomy

A

surgical castration

23
Q

What is used for chemical castration?

A

LHRH agonists

24
Q

How to LHRH agonists work?

A

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

25
example of LHRH agonist
Zoladex (goserelin)
26
How does Zoldex/Goserelin work?
The continuous agonist presence leads to DECREASED levels of LHRH R levels on pituitary gland
27
drug to inhibit AR
Casodex (Bicalutamide)
28
MOA Casodex (Bicalutamide)
– Binds to AR directly – AR STILL ENTERS THE NUCLEUS – Casodex prevents gene transcription - Alter dose depending upon response – PSA test - outcompetes DHT
29
resistance to Casodex (Bicalutamide)
* 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
30
CRPC
* 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
31
relapsed PC Tx
Taxanes - Docetaxal
32
s/e Docetaxal
Neutropenia Anemia Hair loss Fluid retention Diarrhea Nausea Rash Mouth sores Fingernail changes
33
Tx for Castrate Resistant Disease
Enzalutamide
34
Who is Enzalutamide reserved for?
patients with metastasis, CRPC disease
35
Abiraterone MOA
* 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
36
AR variants
* LBD removed, drugs can't bind * resistant to ADT, enzalutamide & abiraterone * resistance to apoptosis
37
Tx for CRPC
Abiraterone & Enzalutamide
38
Why enzalutamise > Bicalutamide (Casodex)?
doesn't become partial agonist when it mutates