30. Prostate Cancer

Question 1

what are some risk factors of prostate cancer

Answer 1

> 40
more common in african americans
men with a single first degree relative with the disease doubles their risk
red meat and saturated fats

Question 2

what systems in the male body is the prostate gland a part of

Answer 2

reproductive and urinary

Question 3

what is the main function of the prostate gland

Answer 3

produce the fluid portion of the semen
- also plays a part in controlling the flow of urine

Question 4

what are some early symptoms of prostate cancer

Answer 4

• rush to the bathroom more frequently or slow flow in urine
• ED
• blood in the urine or semen

Question 5

what are some advanced symptoms of prostate cancer

Answer 5

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

Question 6

these are not diagnostic of prostate cancer but place patients into a higher risk group for having cancer, and require further investigation

Answer 6

abnormal DRE and elevated PSA

Question 7

diagnosis of prostate cancer is confirmed by _______

Answer 7

needle biopsy

Question 8

these may be done to detect any distant metastases

Answer 8

• bone scan
• CT abdomen/pelvis

Question 9

explain the stages of prostate cancer

Answer 9

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

Question 10

what is the best prognostic indicator for prostate cancer

Answer 10

Gleason score (grading)

Question 11

what is the most common cell type of prostate cancer

Answer 11

adenocarcinoma

Question 12

know the different levels of the Gleason score

Answer 12

< 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%)

Question 13

what are the 3 factors that are involved in determining whether stage I and II prostate cancer are low, moderate or high risk

Answer 13

stage, PSA level and Gleason score

Question 14

what is the treatment for stage I prostate cancer

Answer 14

watch and wait + active surveillance (get scan q 3-6 months)
surgery
radiation

Question 15

what is the treatment for stage II prostate cancer

Answer 15

watch and wait + active surveillance (get scan q 3-6 months)
surgery
radiation

Question 16

what is the treatment for stage III prostate cancer

Answer 16

watch and wait (for someone who is older and cannot tolerate tx)
surgery
radiation
hormonal therapy (LHRH agonist)

Question 17

what is the first line treatment for stage IV (metastatic) prostate cancer

Answer 17

androgen deprivation therapy (ADT)

Question 18

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

Answer 18

1st line -> switch to an ARAT (abiratarone, enzalutamide, darolutamide, apalutamide)

2nd line -> chemotherapy (Docetaxel) may be considered

Question 19

what does it mean if a patient is castrate resistant?

Answer 19

while being managed on ADT, they have evidence of disease progession (elevation in serum PSA, new matastases, progression of exisiting metastases)

Question 20

what agents are used in men with prostate cancer who also have bone metastases?

Answer 20

denosumab (Xgeva) or zoledronic acid

Question 21

how does androgen deprivation therapy (ADT) work?

Answer 21

prevents the body from making androgens in the testicles or
blocks effects of the androgens

Question 22

explain how LHRH (or GnRH) agonists work

Answer 22

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

Question 23

how long do you treat prostate cancer with LHRH agonists

Answer 23

long term

Question 24

what are some side effects of LHRH agonists

Answer 24

cardiovascular morbidity (MI risk)
osteoporosis
anemia
muscle loss
hot flashes
sexual dysfunction (decreased libido, ED)
fatigue
lethargy
cognitive impairment

Question 25

explain how LHRH (GnRH) antagonists work

Answer 25

these block the anterior pituitary which leads to rapid suppression of LH and therefore testosterone

Question 26

how long do you treat prostate cancer with LHRH antagonists

Answer 26

long term

Question 27

what are some side effects of LHRH antagonists

Answer 27

cardiovascular morbidity (MI risk)
osteoporosis
anemia
muscle loss
hot flashes
sexual dysfunction (decreased libido, ED)
fatigue
lethargy
cognitive impairment

Question 28

what are the three anti-androgen agents

Answer 28

bicalutamide, flutamide and nilutamide

Question 29

what is an advantage of anti-androgens compared to LHRH agonists/antagonists

Answer 29

they have fewer side effects (less likely to diminish libido)

Question 30

how long do you normally treat prostate cancer with anti-androgens for

Answer 30

used for 7 days upon initial treatment of LHRH agonists

Question 31

true or false: anti-androgens are first line for initial androgen blockage

Answer 31

false - could be used for patients who cannot tolerate LHRH agonist

Question 32

what are some side effects anti-androgens

Answer 32

hot flashes, gynecomastia, constipation or diarrhea

Question 33

explain how androgen receptor antagonists (ARATs) work

Answer 33

inhibit androgen receptor nuclear translocation, DNA binding and coactivator mobillization leading to cellular apoptosis and decreased prostate tumor volume

Question 34

how long do you use ARATs to treat prostate cancer for

Answer 34

hopefully for many years - until disease progression or intolerable adverse effects

Question 35

what are some side effects of ARATs

Answer 35

• fatigue*
• hypertension

Question 36

which ARAT is a substrate of CYP3A4

Answer 36

enzalutamide

Question 37

which ARATs are inducers of CYP3A4

Answer 37

enzalutamide and apalutamide

Question 38

which is the cleaner ARAT in terms of drug interactions

Answer 38

darolutamide

Question 39

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

Answer 39

abiraterone

Question 40

how long do you treat prostate cancer with abiraterone

Answer 40

until disease progression or intolerable effects

Question 41

what are some side effects of abiraterone (CYP 17 inhibitor)

Answer 41

• fatigue
• hypertension
• hypokalmeia
• substrate of 3A4

Question 42

true or false: abiraterone should be taken with food to help with side effects

Answer 42

false - DO NOT ADMINISTER ABIRATERONE WITH FOOD
-can increase systemic exposure up to 10-fold

Question 43

what medication are people usually put on in combination with Abiraterone (hint: not related to treating prostate cancer)

Answer 43

prednisone!
blocking CYP 17 also causes cortisone production to be blocked therefore stopping the negative feedback loop and causing ACTH to be on overdrive