Prostate Flashcards
What is the Gleason score?
A pathological score based on prostate architecture and differentiation
Gleason 2-4 low risk (well differentiated)
Gleason 5-7 intermediate
Gleason 8-10 high risk (poorly differentiated)
What is the deal with prostate cancer screening?
Not recommended as population based programme due to high rates of over diagnosis and treatment
Individuals can make an informed decision regarding the benefits of PSA testing
What are some risk factors for prostate cancer
Age - biggest risk factor, 99% occur in those lord then 50
Family history
BRCA (especially BRCA2 - higher Gleason and worse prognosis)
African Americans
What is PSA and what is the normal range?
Protein released from prostate cells - specific to prostate but not to prostatic malignancy
Normal range 0-4 micrograms/litre
What conditions/situations can cause a high PSA?
Daily variation Prostate cancer Urine infection Urinary retention DRE Prostate massage Prostatitis BPH
In those with an intermediate PSA (4-10) what additional test can be done to determine likelihood of malignancy?
PSA is mostly protein bound, even more so when there is prostate cancer, therefore the free PSA can be measured. If it is less than 10% then malignancy is more likely.
What is recommended to diagnose prostate cancer?
Prostate biopsy - USS or MRI guided
At least 12 cores needed minimum
How is prostate cancer staged?
TNM + Gleason score + PSA
What is the classification of low risk prostate cancer?
PSA less then 10
Gleason less than 6
T1 or T2a (tumour only detected incidentally on biopsy or tumour only involving less than half a lobe of the prostate)
Need all 3 to be low risk
What is the classification of intermediate risk prostate cancer?
Gleason score 7
PSA 10-20
T2b - tumour only involving one lobe of the prostate
Only need one of above to be intermediate risk
What is the definition of high risk disease?
One of:
PSA greater than 20
Gleason 8-10
T2c or greater
When is staging with bone scan/ct cap recommended?
Intermediate and high risk disease
What are the options of treatment for localised disease?
Watchful waiting - in those not eligible for curative treatment, wait until progression occurs then start androgen deprivation treatment
Radical prostatectomy
External beam radiotherapy
Brachytherapy
Active surveillance - watching closely to identify disease progression then starting curative treatment (out of the 3 above)
What treatments are recommended for high risk localised prostate cancer?
Radical prostatectomy with pelvic lymphadectomy
Or radical radiotherapy with both neo-adjuvant and adjuvant androgen deprivation therapy
What are the main treatment options for metastatic carstrate sensitive prostate cancer?
Androgen deprivation therapy
If able to tolerate - 6 cycles of docetaxel chemotherapy with prednisone pre-med
What is androgen deprivation therapy?
Surgical orchidectomy - quick decrease in testosterone
Medical orchidectomy - use GnRH agonists which bind to receptors on the pituitary causing an initial surge in LH and testosterone but then due to constant stimulation leads to down regulation of receptors and low levels of androgens and testosterone
What is “tumour flare” in regards to the treatment of prostate cancer? How is it prevented?
With the initial surge of LH and testosterone get an increase in disease and bone pain over the first few weeks (takes 3-4 weeks to reach castrate levels).
Minimise this by using a anti-androgen (bicalutimide) which blocks the androgen receptor, pre and for a period post commencement of GnRH inhibition
What are some side effects of ADT?
Loss of libido Loss of muscle mass Increased body fat Gynecomastia Mood changes Hot flashes
What indicates development of castrate resistant metastatic disease?
Rising PSA
New metastases
Or increase in growth of existing metastases
What should you do if there is the development of castrate resistance?
First stop the anti-androgen if the patient is on it (anti-androgens can develop agonist activity at the androgen receptor causing rise in PSA and disease progression)
Continue GnRH agonism
Look at starting other treatments
What are some treatment options for castrate resistance prostate cancer?
Abiraterone Enzalutamide Docetaxel with ongoing prednisone Radium -223 Carbazitaxsel
Unsure what order of treatment is preferred - nil evidence yet
What is abiraterone and what is a main caution with its use?
Androgen synthesis inhibitor
Blocks the 2 enzymes that are products of the CYP 17 gene (17,20 lyase and 17 alpha hydroxylase) which stops synthesis of testosterone and androgens
Main caution is development of mineralcorticoid excess as cortisol production is decreased leading to increased ACTH and mineralcorticoid secretion (hypertension, hypokalaemia and fluid retention) This is why it is always given with glucocorticoid
What is enzalutamide?
Androgen receptor blocker that works in multiple locations (ie receptor, nucleus and prevents integration of receptor into cell)
Has no risk of agonist effects unlike first generation androgen receptor blockers (bicalutamide and flutamide)
What is radium-223 and what are its uses?
Radio-labelled radium gets up taken by calcimimetic cells and then emits alpha radiation to target bone mets with minimal toxicity
Good bone targeted therapy
