30. Prostate Cancer Flashcards
what are some risk factors of prostate cancer
> 40
more common in african americans
men with a single first degree relative with the disease doubles their risk
red meat and saturated fats
what systems in the male body is the prostate gland a part of
reproductive and urinary
what is the main function of the prostate gland
produce the fluid portion of the semen
- also plays a part in controlling the flow of urine
what are some early symptoms of prostate cancer
- rush to the bathroom more frequently or slow flow in urine
- ED
- blood in the urine or semen
what are some advanced symptoms of prostate cancer
bone, liver, lung or brain metastasis
- bone metastasis are really common in advanced prostate cancer therefore patients may experience pain in back, hips or upper thighs and possibly fractures
these are not diagnostic of prostate cancer but place patients into a higher risk group for having cancer, and require further investigation
abnormal DRE and elevated PSA
diagnosis of prostate cancer is confirmed by _______
needle biopsy
these may be done to detect any distant metastases
- bone scan
- CT abdomen/pelvis
explain the stages of prostate cancer
stage I: cancer is small and only in the prostate
stage II: cancer is larger and may be in both lobes of the prostate, but still only in the prostate
stage III is locally advanced: cancer has spread beyond the prostate to close by lymph nodes or seminal vesicles
stage IV is advanced or metastatic: cancer has spread to BBLL
what is the best prognostic indicator for prostate cancer
Gleason score (grading)
what is the most common cell type of prostate cancer
adenocarcinoma
know the different levels of the Gleason score
< 4: cancer cells are well differentiated (look like normal cells); ten year risk of local progression is low (25%)
5-7: cancer cells are moderately differentiated
> 7: cancer cells are poorly differentiated (do not look like normal cells); ten year risk of local progression is high (75%)
what are the 3 factors that are involved in determining whether stage I and II prostate cancer are low, moderate or high risk
stage, PSA level and Gleason score
what is the treatment for stage I prostate cancer
watch and wait + active surveillance (get scan q 3-6 months)
surgery
radiation
what is the treatment for stage II prostate cancer
watch and wait + active surveillance (get scan q 3-6 months)
surgery
radiation
what is the treatment for stage III prostate cancer
watch and wait (for someone who is older and cannot tolerate tx)
surgery
radiation
hormonal therapy (LHRH agonist)
what is the first line treatment for stage IV (metastatic) prostate cancer
androgen deprivation therapy (ADT)
what should you do if your patient has been on ADT for their stage IV prostate cancer, and they come back and they have an increase in their serum PSA or new metastasis
1st line -> switch to an ARAT (abiratarone, enzalutamide, darolutamide, apalutamide)
2nd line -> chemotherapy (Docetaxel) may be considered
what does it mean if a patient is castrate resistant?
while being managed on ADT, they have evidence of disease progession (elevation in serum PSA, new matastases, progression of exisiting metastases)
what agents are used in men with prostate cancer who also have bone metastases?
denosumab (Xgeva) or zoledronic acid
how does androgen deprivation therapy (ADT) work?
prevents the body from making androgens in the testicles or
blocks effects of the androgens
explain how LHRH (or GnRH) agonists work
in the beginning, they cause an increase release in LHRH (GnRH0 which stimulates the anterior pituitary gland to produce more FSH and LH which causes the testis to release more testosterone. within about 2 weeks, the LHRH receptors will down regulate and the secretion of LH will decrease, thus decreasing the secretion of testosterone
how long do you treat prostate cancer with LHRH agonists
long term
what are some side effects of LHRH agonists
cardiovascular morbidity (MI risk)
osteoporosis
anemia
muscle loss
hot flashes
sexual dysfunction (decreased libido, ED)
fatigue
lethargy
cognitive impairment
explain how LHRH (GnRH) antagonists work
these block the anterior pituitary which leads to rapid suppression of LH and therefore testosterone
how long do you treat prostate cancer with LHRH antagonists
long term
what are some side effects of LHRH antagonists
cardiovascular morbidity (MI risk)
osteoporosis
anemia
muscle loss
hot flashes
sexual dysfunction (decreased libido, ED)
fatigue
lethargy
cognitive impairment
what are the three anti-androgen agents
bicalutamide, flutamide and nilutamide
what is an advantage of anti-androgens compared to LHRH agonists/antagonists
they have fewer side effects (less likely to diminish libido)
how long do you normally treat prostate cancer with anti-androgens for
used for 7 days upon initial treatment of LHRH agonists
true or false: anti-androgens are first line for initial androgen blockage
false - could be used for patients who cannot tolerate LHRH agonist
what are some side effects anti-androgens
hot flashes, gynecomastia, constipation or diarrhea
explain how androgen receptor antagonists (ARATs) work
inhibit androgen receptor nuclear translocation, DNA binding and coactivator mobillization leading to cellular apoptosis and decreased prostate tumor volume
how long do you use ARATs to treat prostate cancer for
hopefully for many years - until disease progression or intolerable adverse effects
what are some side effects of ARATs
- fatigue*
- hypertension
which ARAT is a substrate of CYP3A4
enzalutamide
which ARATs are inducers of CYP3A4
enzalutamide and apalutamide
which is the cleaner ARAT in terms of drug interactions
darolutamide
this medication selectively and irreversibly inhibits CYP 17, which is an enxyme required for androgen biosynthesis that is expressed in testicular, adrenal and prostatic tumor tissues
abiraterone
how long do you treat prostate cancer with abiraterone
until disease progression or intolerable effects
what are some side effects of abiraterone (CYP 17 inhibitor)
- fatigue
- hypertension
- hypokalmeia
- substrate of 3A4
true or false: abiraterone should be taken with food to help with side effects
false - DO NOT ADMINISTER ABIRATERONE WITH FOOD
-can increase systemic exposure up to 10-fold
what medication are people usually put on in combination with Abiraterone (hint: not related to treating prostate cancer)
prednisone!
blocking CYP 17 also causes cortisone production to be blocked therefore stopping the negative feedback loop and causing ACTH to be on overdrive
