prostate cancer Flashcards
What is the epidemiology of prostate cancer *(
1 in 8 men get it in their lifetime - most common male-specific cancer in west
49000 new cases a year in England
incidence increased hy 44% since 1990
good mortality - 10yr LE is 80% - but because of the high incidence this is actually a lot of people (more deaths for men by prostate, than women by breast)
3rd highest mortality (1st colorectal, then prostate, then breast)
lung cancer highest mortality in men followed by prostate
when age 60 there is a dramatic increase in diagnosis - increase in prevalence of latent and clinically detected prostate cancer - only 5% of deaths occuring in men are under 64yrs - however increase in incidence is not soley due to the increasing population
incidence predicted to raise by 12% in the UK between 2-14 and 2035 to 233 cases per 100000 males
what are the symptoms of prostate cancer *
Difficulty urinating – prostate surrounds the urethra so if enlarges put pressure on urethra
More frequent and feeling of urgency – then when go difficulty and retention in bladder
rarely lower back pain/blood in the urine
what is the problem with interpretation of the symptoms for prostate cancer *
Prostate enlarges in completely healthy people – get some of these symptoms, doesn’t mean you have cancer
this is BPH (benign prostatic hyperplasia) - have milder symptoms than if you had a tumour
what are the tests for prostate cancer *
digital rectal examination
PSA - prostate specific antigen
then biopsy - MRI done at same time, newer methods of multi-parameter MRI are being tested to avoid invasive biopsy
describe the PSA test *
blood test - immunoassay on the serum
any enlargement of prostate = leakage of PSA into the blood
therefore can be raised with:
- BPH
- UTI (but would get pain when urinating)
- inflammation
- mechanical damage - bike ride/biopsy
- prostatitis - infection of the prostate
if >4ng/ml then have to do something to see if it is cancer (ie biopsy, can rise to 2000 ng/ml and above in aggressive metastatic disease.
describe biopsy for prostate cancer *
TRUS - transrectal and US
prostate is very close to the intestinal wall so go through the wall and take 10cores - send to lab
look under microscope and grade the tumour - this is the Gleason’s grading system
biopsy can under and overestimate the tumour grade - extended sampling techniques and repeat biopsies have improved this
what are the SE of biopsy *
infection so take AB prophylactically
bleeding in urine for a time
what are the 4 types of treatment for prostate cancer *
surgery
radiotherpay
hormone therapy
chemotherapy
describe surgery for prostate cancer *
fine for localised tumours
have to remove whole prostate - this is radical prostectomy, it is done laparoscopically with robots
takes 4-5 hrs - major surgery
have to have PSA <10-12ng/ml and age <70yrs - giving the group with the highest survival
describe the side effects of surgery for prostate cancer *
incontinence - because have to cut urethra to be able to remove all prostate then reattach around the catheter, then have catheter removed - at this point you hvae incontinance for 2months so told to do pelvic floors
sterility - can freesze eggs (not always important because most people are >60)
impotence - loss of erectile function, reason why people dont want surgery - this is because the nerves are removed, can do nerve sparing tumour but less likely to be able to remove all the tumour
describe radiotherapy for prostate cancer *
external beam radiotherapy - focus onto a particular place to try and destroy the tissue - possible if spread out of prostate capsule but not affected the other organs, computer planning is used to limit the toxicity to the bowel and bladder
or, if tumour contained in prostate - brachytherapy - radiactive seeds inserted into tissue so localised source of radiation in tissue
requires multiple visits - every day for a month
what are the side effects of radiotherapy for prostate *
incontinence,
erectile dysfunction,
diarrhoea (because the radiotherapy effects the gut)
when is hormone therapy used *
Used in combination eg radiotherapy – shrink the tumour so easier to focus the beam on the right place
describe the hormone axis to the prostate *
Hypothalamus produces GnRH (also called LHRH)
Bind to pituitary – cause pit to release LH
Act on testes - testes produce androgen
Androgen act on prostate
mechanism of action of hormone therapy for prostate cancer *
bilateral orchidectomy (remove the source of testosterone ie the testes) - this is done chemically:
LHRH agonists (eg leuroprorelin) – stimulate the LHRH receptors = overstimulation = downregulation or receptors – cant respond to endogenous hormone (injection every month)
problem is the cancer will get worse initially because of the ‘testosterone flare’ due to increased LHRH stimulation until the receptors are downregulated
to address this - give anti-androgen (flutamide), this combats the other androgens that are produced by the adrenal glands
Abiraterone - CYP17 inhibitor blocks synthesis of androgens – given to men with metastatic prostate cancer (tablets once a day)
there are LHRH antagonists but less effective
describe chemotherapy for prostate cancer *
treatment of last resource – giving a few months extra life, often people don’t want it at this point because of the SE
how can we monitor the effectiveness of therapies *
PSA would go down dramatically (if surgery to undetectable – therefore people like this because easy to see if it has come back)
If other therapies 1st not as dramatic decline so harder to know if it has come back
describe the gleason’s gradig system *
it is a commonly used histopathological reporting of prostate cancer
the 2 largest areas of tumour found are scored 1-5 (1 is least agressive, 5 is most) - the 2 scores are quoted plus their sum
sums 2-4 are low grade
5-7 - intermediate
8-10 high
can you tell whether a prostate tumour is slow/fast growing from genetics *
no - there is not a relation between mutations and speed of growth
do metastasing prostate cancer cells also produce PSA *
yes
What could a PSA test result of 15ng/ml indicate?
prostate cancer or infection
why would someone be offered hormone therapy over surgery *
age - so LE and QOL – someone who is 60 more likely to have longer with better QOL than someone 78, long operation under GA that has some risk – older people with longer operation effect mental faculties
what mechanism could contribute to recurrance of prostate cancer in spite of continued anti-androgen treatment *
biochemical relapse happens in 13months, symptomatic in 2yrs and death 7months later
tumour develops independent of androgen - however the expression of the androgen receptor (the ligand activated TF that mediates response to androgens is not lost and is often increased by over expression or gene amplification - implying androgen receptor signalling is required for prostate cancer progression
there could be amplifications of the response to low residual levels of androgens, or weak androgens present in patient by increased levels of androgen receptor or other proteins required for androgen receptor signalling (co-activators), decreased level of co-repressors, or mutation of the androgen receptor so it is stimulated by other ligands - oestrogens or anti-androgens
the mutations are rare in primary tumours, increase in frequency in advanced, metastatic hormone-independant disease - they are in 30-50% of these tumours; amplication or overexpression of the androgen receptor is seen in a similar proportion
amplication of co-activator proteins has been seen in breast cancer and has been studied in prostate cancer
another pathway could be ligand-independant activation of the androgen receptor by GF eg in ER in breast cancer
or the androgen receptor could be bypassed altogether by loss of PTEN for eg
eg because of mutations in androgen receptors or signalling pathway from androgen receptor
hormone therapy selects out mutants so PSA starts increasing so might want to start chemo.
dont have to do each type of therapy in isolation
how we can go about searching for markers of aggressive versus latent prostate cancer *
genetic approach (RNA or DNA) but don’t know from just biopsy which is aggressive, need clinical info as well.
Ideally less invasive way – cfDNA (tumour cells release small amounts of DNA into the blood), take blood sample and will be able to see what type of prostate tumour it might be
