Prostate Cancer Flashcards

1
Q

purpose of the prostate`

A

produce seminal fluid + urine flow control

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2
Q

prostate cell function, growth, and differentiation depensd on

A

androgen hormones

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3
Q

where is most testosterone made?

A

testes

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4
Q

where are sites of T production

A

testes
adrenal glands
can be in any tissue for men

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5
Q

___________ is foundational molecule for T, glucocorticoids, mineralocorticoids

A

Cholesterol

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6
Q

_______: critical enzyme for conversion of pregnenolone/ progesterone to androgens or cortisol

A

CYP17

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7
Q

T from testes converted to DHT in prostate cell and activates androgen receptor = cell growth/ proliferation, prevents apoptosis, increase in ____________

A

prostate specific antigen (PSA)

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8
Q

what is PSA

A

prostate specific antigen- protein produced by both cancerous and noncancerous prostate tissue

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9
Q

PSA normal levels are

A

0-4ng/mL, increases with age

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10
Q

<10ng/mL PSA means

A

low risk

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11
Q

10-20ng/mL PSA menas

A

intermed risk

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12
Q

> 20ng/mL PSA or a rapid increase means

A

high risk

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13
Q

what are some limitations of using PSA

A

No PSA level excludes PC
Low PSA thresholds for further investigations increases false + = overdiagnosis
Low specificity: PSA can be elevated for several reasons, not just cancer

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14
Q

T or F: prostate cancer is recommended for those 50-74yrs

A

F- individualize decision with dr after 50yrs old

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15
Q

when is PSA screening more likely to be recommended

A

higher risk- african, father/ brother with PC, genetic disposition

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16
Q

prostate cancer screening can include

A

PSA, digital rectal exam

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17
Q

T or F: PSA and DRE are not diagnostic, they can only risk stratify

A

T- only a biopsy can diagnose

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18
Q

list 3 prostate cancer RFs

A

> 65yrs
african
fam hx (2x)
germline mutations (BCRA 1 or 2, lynch syndrome)
high meat/ fat diet, vit E
hormonal high T
smoking

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19
Q

sx of local PC

A

Asymptomatic
Ureteral dysfunction (frequency, hesitancy, dribbling)
Impotence

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20
Q

sx of advanced PC

A

Back pain, cord compression, fractures (bone = most common site of metastasis)
Anemia
Weight loss

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21
Q

what is stage 1-2 PC

A

confined to prostate

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22
Q

what is stage 3 PC

A

large tumor or extraprostatic tumor possible invading adjacent structures

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23
Q

how is prostate cancer graded?

A

based on histologic appearance with the gleason and grade score

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24
Q

what is the gleason score

A

2 scores from 2 samples added together

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25
Q

what is the grade group

A

2 scores from histologic appearance added together

26
Q

what is the natural progression of prostate cancer

A

CSPC will eventually overcome T deprivation and make its own T = CRPC

27
Q

what is a radical prostatectomy? what are the SEs

A

Radical prostatectomy (RP): surgical removal of prostate gland + surrounding tissues (including seminal vesicles)
AEs: urinary incontinence, ED - if nerve sparing then 50-80% regain sexual potency within the first year

28
Q

what is PLB

A

Pelvic lymph node biopsy (PLNB): done with RP if pt deemed high risk of lymph node metastasis

29
Q

what is an orchiectomy

A

surgical castration- rarely done

30
Q

what pharm meds can be used for nonmet PC

A

LHRH agonists
GnRH antagonists
antiandrogens
novel hormone manipulation therapies

31
Q

most common LHRH agonist used in PC

A

leuprolide

32
Q

leuprolide class

A

LHRH

33
Q

leuprolide AEs

A

osteoporosis/ fractures due to hypogonadic state (monitor BMD + calcium and vit D (unless hypercalcemic), drug induced disease flare, decreased libido, impotence, hot flashes, depression, ↑cholesterol

34
Q

degarelix class

A

GnRH antagonists

35
Q

GnRH ant AEs

A

hot flashes, injection site pain, QTc interval prolongation, reduced libido, ED

36
Q

nonsteroidal antiandrogens include

A

bicalutamide, nilutamide, fluatmide

37
Q

steroidal antiandrogens include

A

cyproterone

38
Q

why are antiandrogens rarely used as monotherapy

A

Rarely monotherapy as feedback loops will overcome suppressive effects + inferior to LHRH agonist

39
Q

antiandrogen place in PC

A

start just before LHRH agonist F4wks to prevent flare response

40
Q

antiandrogen AEs

A

gynecomastia, breast tenderness, hot flashes, fatigue, diarrhea

41
Q

novel hormone manipulation therapies include

A

Enzalutamide, apalutamide, darolutamide + combo with ADT (LHRH analog or orchiectomy)

42
Q

enzalutamide MOA

A

acts at several steps in androgen receptor signaling pathway
Competitively inhibits binding of androgens to receptors with more affinity than older antiandrogen agents like bicalutamide
Inhibits nuclear translocation of androgen receptors, DNA binding, and coactivator recruitment

43
Q

enzalutamide is for

A

nm-CRPC, m-CRPC, m-CSPC

44
Q

apalutamide is for

A

nm-CPRC, m-CSPC

45
Q

darolutamide is for

A

For nm-CPRC

46
Q

notable SEs of enzalutamide

A

QT prolongation
crosses BBB = inhibits GABA and lowers seizure threshold
elevates liver enzymes

47
Q

notable AEs of apalutamide

A

hyperglycemia
HPTN
elevated lipids
QT prolongation
crosses BBB = inhibits GABA and lowers seizure threshold
elevates liver enzymes

48
Q

pharm options for metastatic PC

A

abiraterone
enzalutaide
apalutamide
chemo

49
Q

abiraterone is a

A

selective irrev CYP17i + active in testicular, adrenal, and prostate tumor tissue = cancer can’t make more T

50
Q

abiraterone should be taken ______ while prednisone should be taken _______
1. with food
2. without food

A

2, 1

51
Q

pAEs of abiraterone

A

diarrhea, elevated LFTs (monitor for hepatotoxicity)
Inhibition of CYP17 = ↓cortisol and T = ↑ACTH and aldosterone
High mineralocorticoids and low corticosteroids = must give prednisone 5mg BID to make up for lack of cortisol (take prednisone with food)
Mineralocorticoid effects: peripheral edema, HPTN, hypokalemia, monitor BP, K+, cholesterol

52
Q

what must be given with abiraterone? why?

A

prednisone to make up for lack of cortisol

53
Q

what chemo is used for metastatic PC

A

taxanes- docetaxel + prednisone

54
Q

options for m-CRPC if no prior novel hormone therapy + no chemo

A

docetaxel
abiraterone
enzalutamide

55
Q

options for m-CRPC if prior novel hormone therapy

A

docetaxel

56
Q

options for m-CRPC if prior docetaxel only

A

abireterone, enzalutamide, cabazitaxel

57
Q

options for m-CRPC if prior chemo + prior novel hormone therapy

A

cabazetaxel
possibly docetaxel again if responded well + enough time passed

58
Q

options for m-CSPC if no prior novel hormone therapy + no chemo

A

docetaxel
abiraterone
enzalutamide
apalutamide

59
Q

options for m-CSPC prior novel hormone therapy

A

docetaxel

60
Q

options for m-CSPC prior docetaxel only

A

abireterone, enzalutamide, apalutamide, cabazitaxel

61
Q

options for m-CSPC if prior chemo + prior novel hormone therapy

A

cabazitaxel, possibly docetaxel again if responded well + enough time passed