Prostate Cancer Flashcards
What are the risk factors for prostate cancer?
- >50 - Black - Family hx - High levels of dietary fat - North American or northwest European
What genes are associated with prostate cancer?
Homebox gene HOXB13 = predisposition gene
BRCA 1 & 2
What % of 80 year old men have histological signs of prostate cancer?
80%
What is the lifetime risk of prostate cancer?
1 in 6
Where in the prostate do cancers most commonly develop?
- 75% occur in the peripheral zone
- 20% in the transitional zone
- 5% in the central zone
What is the most likely histological precursor of prostate cancer?
High grade intra-epithelial neoplasia (PIN)
Characterised by cellular proliferation within pre-existing ducts and glands with cytological changes indicating neoplasm
Discuss clinical staging of prostate tumours
Tx: primary tumour cannot be assessed
T0: no evidence of primary tumour
T1: clinically inapparent tumour, not palpable (only found after histology)
T2: tumour palpable and within prostate
T3: extra-prostatic tumour that is not fixed or does not invade adjacent structures e.g. seminal vesicle(s)
T4: tumour is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles and or pelvic wall
Discuss pathological staging of prostate cancer
T2: organ confined
T3: extraprostatic extension
T4: invades structures other than seminal vesicles
What is the function of the prostate gland?
- Exocrine gland
- Secretes prostatic fluid which is alkaline and helps neutralise vaginal acidity
- Comprises 30% of the ejactulate
What is PSA?
Prostate specific antigen
- A protease that functions to make the semen more liquid
- Produced by the epithelial prostatic cells and secreted into the seminal fluid where it is involved in liquefaction of the seminal coagulum
Discuss the causes of a raised PSA
- Prostate cancer
- BPH
- Prostatitis
- UTI
Prostate injury
- Surgery
- Ejaculation
What is a normal PSA level?
>4.0 ng/mL
What should the PSA be in men under 50?
<2.5ng/mL
A PSA of >10ng/mL will show cancer in 50%
Discuss risk levels for prostate cancer
Low risk: T2a, Gleason 6, PSA <10
Medium risk: T2b, Gleason 7, PSA 10-20
High risk: T3a+, Gleason 8, PSA >20
Discuss ISUP grading
Grade 1 - Gleason score of 6 or less
Grade 2 - Gleason score of 7 (3+4)
Grade 3 - Gleason score of 7 (4+3)
Grade 4 - Gleason score of 8
Grade 5 - Gleason score of 9-10
Discuss Gleason’s pattern scale
Obtained by analysing the histology from two separate areas of tumour and adding the scores together
Discuss free PSA
A free PSA >10% suggests the presence of agressive cancer
Discuss the diagnostic approach for prostate cancer
- DRE
- PSA test
- If PSA above their age-specific reference range, urgent 2 week cancer referral
- Guidelines recommend a biopsy for men with a PSA >3ng/L
- Biopsy: 10-12 cores
Discuss the link between testosterone and prostate cancer
- Men with lower testosterone levels are less likely to develop prostate cancer than those with high levels
What are the 1st order investigations for prostate cancer?
- PSA
- Testosterone
- LFTs
- FBC
- Renal function
- Biopsy
What should be done if a prostate biopsy is negative despite a raised PSA?
Close follow up with DRE and repeat PSA within 6-12 months of the biopsy
Discuss treatment of low risk prostate cancer
Low risk: surveillance (Gleason score of 6 or less), xRT, prostatectomy, androgen deprivation therapy
xRT is preferred by older men
Discuss androgen deprivation in prostate cancer
Removal of testosterone blocks that growth of prostate caner but doesn’t cure it
a) GnRH agonists: goserelin and leuprorelin are orchidectomy are equally affective at lowering circulating androgens
*GnRH androgens cause a rise in LH and testosterone during the first week of use and can cause worsening of metastatic disease and must be combine with an anti-androgen such as flutamide
b) Androgen receptor blockers: biclutamide and enzalutamide
c) Androgen synthesis inhibitors: abiraterone which functions by inhibiting CYP17
d) Corticosteroids and oestrogens: useful in disease that has become refractory to castration
Where does prostate cancer most commonly metastasise to?
Bones
Lungs, LNs, Liver and brain
Discuss signs of prostate cancer remote to the prostate
- Back pain, hips, thighs and other bones
- Oedema
- Weight loss
- Fatigue
- Change in bowel habits
- Haematuria
- Decline in renal function
What is the half life of PSA?
2.2-2.3 days
Declines to original value after 4-8 weeks
What is bicalutamide?
Non-steroidal anti-androgen
- Androgen receptor blocker, prevents the binding of adrenal and testicular androgens and thus inhibits prostatic growth
What is goserelin?
Potent inhibitor of pituitary gonadotropin secretion
What is flutamide?
Blocks the action of both endogenous and exogenous testosterone by binding to the androgen receptor
Capable of inhibiting prostatic nuclear uptake of androgen
What are the side effects of androgen suppression therapy?
- Hot flushes
- Loss of libido
- Weight gain
- Metabolic syndrome
- Loss of bone density
- CV side effects
- Cogitive decline
- Difficulty controlling blood glucose
What advice can be given to asymptomatic men asking for a PSA blood test?
- The test is not very accurate and we cannot say that those having the test will live longer - even if they do have prostate cancer
- Most men with prostate cancer die from an unrelated cause
- If the test is falsely positive they will need further testing e.g. prostate sampling which can cause bleeding and infection
- Only 1/3 of people with a raised PSA will have prostate cancer
- If cancer is found and treatment begun, the treatment may cause more harm than the cancer
- Ultimately the decision is the patient’s
How can metastatic prostatic cancer be treated?
- Orchidectomy, most men refuse
