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Flashcards in Prostate cancer tutorial Deck (29)
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1

Epidemiology of prostate cancer in males in UK

most common cancer in UK males. 2nd mortality after lung cancer. Has had an increasing incidence

2

Causes of prostate cancer

hetergoeneous, environments and genetics

3

Hypotheses for cause of familial (genetic) prostate cancer

PTEN (tumour suppressor gene) inactivation leading to autonomous activation of androgen receptor (shown to antagonise androgen receptor signalling pathway) or facilitates anti-apoptotic pathways

4

Clinical presentation of prostate cancer

Problems urinating
less common lower back pain and haematuria

5

Normal physiological role of prostate gland

exocrine gland, production of seminal fluid released into prostatic part of urethre, component of ejaculate, necessary for male fertility

6

frequent sites of metastasis of prostate cancer

seminal vesicles, bladder
lymph nodes and bones

7

What is PSA?

Prostate specific antigen

8

describe and explain Normal PSA levels in blood

Normally undetectable PSA due to inability to pass through gap junctions/BM of luminal ep cells of prostate

9

Describe and explain PSA levels in prostate cancer/BPH

Elevated due to hyperplasia and leakage into blood so detectable (cancer usually grows disorganised so lack of junction/invasion past BM)

10

WHat is BPH? Who does usually affect?

Benign prostatic hyperplasia
Hyperplasia of prostate gland not associated with malignancy
Most >50y males

11

What is the cut off for PSA above which further investigation need to be conducted?

4ng/ml serum

12

Reasons for elevated PSA not cancer

bike riding, exercise, UTI, post-biopsy, prostatitis, anal sex

13

Tests done after +ve elevated PSA

biopsy and tumour grading, digital rectal exam, MRI scan

14

Scoring system used to grade prostate cancers

Gleason score

15

Nature of prostate cancers

slow-growing "pussycats" or aggressive "tigers" and life-threatening due to throwing off metastases that usually cause bone involvement

16

"treatment" for low grade/slow growing prostate malignant cancer

nothing, watchful waiting by doing regular tests

17

Treatments of prostate cancers confined to prostate gland exclusively

Radical prostatectomy surgery (highest survival PSA<10-12ng/ml and <70yo)
Targeted external beam radiotherapy
Brachytherapy = implantation of radioactive seeds into prostate

18

SE of prostatectomy/radiotherapy/brachytherapy

inontinence, pudendal nerve damage -> impotence

19

Principle for hormone therapy in prostate cancer

Androgens stimulate prostatic growth via androgen receptor, so can be used to halt tumour progression/growth

20

Treatment options in hormone therapy and explanation

Chemical bilateral orchidectomy causing most androgen production to cease
Anti-androgens

21

Mechanism of Chemical bilateral orchidectomy

LHRH agonist used
Causes desenitisation of pituiatry gonadotrophs, so LH production ceases and testosterone/androgen prod also ceases

22

MOA of antiandogens

Androgen receptor antagonists

23

SE of hormone therapy

osteoporosis, loss of libido, muscle atrophy, memory loss, gynaecomastia

24

Explain androgen independence in prostate tumours after effective hormone therapy

Prostate cancers can become symptomatic and usually more aggressive after hormone therapy

25

Mechanisms of androgen indepence

Androgen receptor overexpression -> amplifieed response to remaining circulating weak androgens
Androgen receptor structural change -> activity change, activated by other ligands eg oestrogen
Upregulation of signalling molecules in androgen receptor
Target gene amplification
Decreased levels of co-repressors (antagonists)

26

Examples of antiandrogens

Flutamide, Nilutamide

27

Scoring system used in prostate cancer

Gleason scoring system

28

Describe the Gleason scoring system
How is the Gleason score quoted and what does it mean?

Gleason is a scale from 1-5. 1 being identical to prostate gland = small uniform glands, 5 being undifferentiated, unrecognizable. The higher the score, the worse the prostate cancer and the worse the prognosis

It is quoted as 2 numbers on the scale and their total
eg 3+4=7
the first number refers to the majority score of the biopsy and the second to the second most prervalent

29

Why does the Gleason score quote 2 numbers?

Prostate cancer differentiation is highly variable (which is also why many biopsies are taken from multiple parts of the gland)