Prostate Cancer Flashcards by Linda Chen

purpose of the prostate`

produce seminal fluid + urine flow control

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prostate cell function, growth, and differentiation depensd on

androgen hormones

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where is most testosterone made?

testes

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where are sites of T production

testes
adrenal glands
can be in any tissue for men

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___________ is foundational molecule for T, glucocorticoids, mineralocorticoids

Cholesterol

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

CYP17

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

prostate specific antigen (PSA)

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what is PSA

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

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PSA normal levels are

0-4ng/mL, increases with age

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<10ng/mL PSA means

low risk

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10-20ng/mL PSA menas

intermed risk

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> 20ng/mL PSA or a rapid increase means

high risk

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what are some limitations of using PSA

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

F- individualize decision with dr after 50yrs old

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when is PSA screening more likely to be recommended

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

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prostate cancer screening can include

PSA, digital rectal exam

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

T- only a biopsy can diagnose

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list 3 prostate cancer RFs

> 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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sx of local PC

Asymptomatic
Ureteral dysfunction (frequency, hesitancy, dribbling)
Impotence

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sx of advanced PC

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

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what is stage 1-2 PC

confined to prostate

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what is stage 3 PC

large tumor or extraprostatic tumor possible invading adjacent structures

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how is prostate cancer graded?

based on histologic appearance with the gleason and grade score

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what is the gleason score

2 scores from 2 samples added together

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what is the grade group

2 scores from histologic appearance added together

what is the natural progression of prostate cancer

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

what is a radical prostatectomy? what are the SEs

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

what is PLB

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

what is an orchiectomy

surgical castration- rarely done

what pharm meds can be used for nonmet PC

LHRH agonists GnRH antagonists antiandrogens novel hormone manipulation therapies

most common LHRH agonist used in PC

leuprolide

leuprolide class

LHRH

leuprolide AEs

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

degarelix class

GnRH antagonists

GnRH ant AEs

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

nonsteroidal antiandrogens include

bicalutamide, nilutamide, fluatmide

steroidal antiandrogens include

cyproterone

why are antiandrogens rarely used as monotherapy

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

antiandrogen place in PC

start just before LHRH agonist F4wks to prevent flare response

antiandrogen AEs

gynecomastia, breast tenderness, hot flashes, fatigue, diarrhea

novel hormone manipulation therapies include

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

enzalutamide MOA

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

enzalutamide is for

nm-CRPC, m-CRPC, m-CSPC

apalutamide is for

nm-CPRC, m-CSPC

darolutamide is for

For nm-CPRC

notable SEs of enzalutamide

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

notable AEs of apalutamide

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

pharm options for metastatic PC

abiraterone enzalutaide apalutamide chemo

abiraterone is a

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

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

2, 1

pAEs of abiraterone

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

what must be given with abiraterone? why?

prednisone to make up for lack of cortisol

what chemo is used for metastatic PC

taxanes- docetaxel + prednisone

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

docetaxel abiraterone enzalutamide

options for m-CRPC if prior novel hormone therapy

docetaxel

options for m-CRPC if prior docetaxel only

abireterone, enzalutamide, cabazitaxel

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

cabazetaxel possibly docetaxel again if responded well + enough time passed

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

docetaxel abiraterone enzalutamide apalutamide

options for m-CSPC prior novel hormone therapy

docetaxel

options for m-CSPC prior docetaxel only

abireterone, enzalutamide, apalutamide, cabazitaxel

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

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