Prostate cancer Flashcards
What does the prostate gland do
secretes fluid that nourishes and protects the sperm
during ejaculation prostate squeeces fluid into the urethra
• Prostate located below the bladder
- Connected to seminal vesicles
- The urethra passes through the prostate
• Prostate cancer only develops in men
• The vasa deferentia bring sperm from the testes to seminal vesicles. The seminal vesicles contribute fluid to semen during ejaculation.
Prostate gland - peripheral zone
the prostate gland is divided into several zones, peripheral zone is >70% of prostate tissue - largest contribution to normal function
also most common site of origin of prostate tumours
Prostate enlargement
benign prostatic hyperplasia (another name)
common as men get older
if prostate gland gets too big it can block urine flow out of bladder
Prostate cancer epidemiology
second most common cancer cause
leading cause of cancer associated death in men
risk increases with age
more common in caribbean and african men
less common in asian men
localised disease has 99% - 10 year survival if detected early
Prostate cancer diagnosis
Prostate specific antigen (PSA) blood test.
- PSA exists in normal ranges in males (1-2 nanograms)
- High PSA = signs of prostate cancer
- Not the most accurate, as high levels of PSA can be triggered by other factors (e.g. exercise)
Prostate examination (digital rectal examination-DRE).
- Can do further tests to confirm for prostate can if PSA levels are high
MRI and ultrasounds scans.
- Only if the doctors find a lumpy mass
Biopsies.
- Get sample to diagnose if something abnormal found in the scan
Different types of prostate cancer
Acinar adenocarcinoma - develops in gland cells that line the prostate gland - most common cancer
ductal adenocarcinoma - starts in cells that line the ducts of prostate gland - spreads quicker and more lethal than acinar
Prostate cancer metastasis
• As the disease progresses = metastasis in other sites
- Prostate is in the pelvic bone
- Pelvic bone metastasis = leads to spinal metastasis / bone metastasis
• The further metastasis has spread = less chance of survival
• Close metastasis = more common
• Further away metastasis = less common
Prostate cancer genetic alterations
- Fusion of ETS genes = transcription factor for erythrocytes (red blood cells)
- Tumour suppressor genes (PTEN or tp53) can be mutated / deleted
- Amplification / activation of MYC oncogene
- As we go to more severe metastatic disease = leads to amplifications of mutations of AR & BRCA genes (major role in prostate cancer)
ar = androgen receptor
Prostate cancer STATUS
Localised prostate cancer - cancer completely inside prostate = has not spread and is treatable
Castrate-sensitive prostate cancer - cancer controlled by keeping testosterone level as low as if testicles were removed (castrate level)
cancer that stops growing if you control testosterone = chemical castration
as cancer progresses you get
castrate resistant prostate cancer - cancer growing even when testosterone leevels are below castrate level
hormone refractory prostate cancer - cancer no longer helped by any type of hormone therapy
hormone and cancer resistant are the same thing
What is the TNM stage
TNM = Tumour lymph node metastasises
0n = no tumour in lymph node 1n = tumour in lymph node m0 = no metastasis m1 = metastasis
Prostate cancer management
• Localised = usually want active surveillance / surgery to remove prostate gland
- Or you can have some radiation
• As the disease progresses (CSPC):
- Can have hormone therapy to control testosterone levels, known as ADT
- Or
- You can have other hormonal drugs to help slow down disease progression when the cancer becomes metastatic
When you become CRPC = hormone therapy is not enough, can use other dugs e.g. localise radiation, doctaxel, PARPi etc
For localised disease - non pharmaceutical treatment options
Active surveillance: PSA, DRE (digital rectal examination), imaging/biopsies (to see if the disease is stable).
- Monitor disease without treating it (done after a certain age e.g. 80+)
Radiotherapy: (shrink the tumour)
external beam radiation (EBRT)
brachytherapy (internal radiation) – (nucleotides / seeds that slowly release radiation in the prostate gland).
Radical prostatectomy: entire prostate gland plus tissue around it is removed (most common)
- So disease doesn’t come back & tissue removed so cancer doesn’t spread
Pelvic lymph node dissection (PLND).
- Very close to prostate = prevents metastasis
How do androgens affect prostate cells
Androgens (testosterone) stimulate prostate cancer cells to grow
naturally produced by men
How can you reduce androgens? pharmacological treatment
androgen deprivation therapy
could remove testicles
lutenizing hormone-releasing hormone (LHRH) agonists/antagonists (basically hormone therapy)
When cancer becomes resistant to ^ then you use ARSI
ARSI - androgen receptor signalling inhibitor- prevent androgen function
examples of ARSI:
Abiraterone (inhibits synthesis of andorgens by inhibiting enzymes)
androgen receptor antagonists - enzalutamide
LHRH vs ARSI
• LHRH antagonist = blocks luteinising hormone (LH)
- Therefore, no signal being produced = no testosterone production
• LHRH agonist = stimulates production of LH (LH causes testosterone production)
- Due to too much stimulation of LH = too much testosterone being produced = creates negative feedback loop
- = desensitisation of LH receptor = no LH effect on LH receptor (no testosterone produce)
• ARSI (abiraterone) = inhibits the production of Androgens by inhibiting CYP17 enzyme, that is involved in the production of (androgen) testosterone (enzymatic inhibition)
• AR receptor antagonist (ARA) e.g. Enzalutamide – blocks AR receptor
- Therefore, increase levels of testosterone won’t be able to bind in the AR receptor
