Prostate cancer tutorial

Question 1

Epidemiology of prostate cancer in males in UK

Answer 1

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

Question 2

Causes of prostate cancer

Answer 2

hetergoeneous, environments and genetics

Question 3

Hypotheses for cause of familial (genetic) prostate cancer

Answer 3

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

Question 4

Clinical presentation of prostate cancer

Answer 4

Problems urinating

less common lower back pain and haematuria

Question 5

Normal physiological role of prostate gland

Answer 5

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

Question 6

frequent sites of metastasis of prostate cancer

Answer 6

seminal vesicles, bladder

lymph nodes and bones

Question 7

What is PSA?

Answer 7

Prostate specific antigen

Question 8

describe and explain Normal PSA levels in blood

Answer 8

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

Question 9

Describe and explain PSA levels in prostate cancer/BPH

Answer 9

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

Question 10

WHat is BPH? Who does usually affect?

Answer 10

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

Question 11

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

Answer 11

4ng/ml serum

Question 12

Reasons for elevated PSA not cancer

Answer 12

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

Question 13

Tests done after +ve elevated PSA

Answer 13

biopsy and tumour grading, digital rectal exam, MRI scan

Question 14

Scoring system used to grade prostate cancers

Answer 14

Gleason score

Question 15

Nature of prostate cancers

Answer 15

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

Question 16

“treatment” for low grade/slow growing prostate malignant cancer

Answer 16

nothing, watchful waiting by doing regular tests

Question 17

Treatments of prostate cancers confined to prostate gland exclusively

Answer 17

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

Question 18

SE of prostatectomy/radiotherapy/brachytherapy

Answer 18

inontinence, pudendal nerve damage -> impotence

Question 19

Principle for hormone therapy in prostate cancer

Answer 19

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

Question 20

Treatment options in hormone therapy and explanation

Answer 20

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

Question 21

Mechanism of Chemical bilateral orchidectomy

Answer 21

LHRH agonist used

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

Question 22

MOA of antiandogens

Answer 22

Androgen receptor antagonists

Question 23

SE of hormone therapy

Answer 23

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

Question 24

Explain androgen independence in prostate tumours after effective hormone therapy

Answer 24

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

Question 25

Mechanisms of androgen indepence

Answer 25

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)

Question 26

Examples of antiandrogens

Answer 26

Flutamide, Nilutamide

Question 27

Scoring system used in prostate cancer

Answer 27

Gleason scoring system

Question 28

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

Answer 28

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

Question 29

Why does the Gleason score quote 2 numbers?

Answer 29

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