Prostate Cancer Flashcards
purpose of the prostate`
produce seminal fluid + urine flow control
prostate cell function, growth, and differentiation depensd on
androgen hormones
where is most testosterone made?
testes
where are sites of T production
testes
adrenal glands
can be in any tissue for men
___________ is foundational molecule for T, glucocorticoids, mineralocorticoids
Cholesterol
_______: critical enzyme for conversion of pregnenolone/ progesterone to androgens or cortisol
CYP17
T from testes converted to DHT in prostate cell and activates androgen receptor = cell growth/ proliferation, prevents apoptosis, increase in ____________
prostate specific antigen (PSA)
what is PSA
prostate specific antigen- protein produced by both cancerous and noncancerous prostate tissue
PSA normal levels are
0-4ng/mL, increases with age
<10ng/mL PSA means
low risk
10-20ng/mL PSA menas
intermed risk
> 20ng/mL PSA or a rapid increase means
high risk
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
T or F: prostate cancer is recommended for those 50-74yrs
F- individualize decision with dr after 50yrs old
when is PSA screening more likely to be recommended
higher risk- african, father/ brother with PC, genetic disposition
prostate cancer screening can include
PSA, digital rectal exam
T or F: PSA and DRE are not diagnostic, they can only risk stratify
T- only a biopsy can diagnose
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
sx of local PC
Asymptomatic
Ureteral dysfunction (frequency, hesitancy, dribbling)
Impotence
sx of advanced PC
Back pain, cord compression, fractures (bone = most common site of metastasis)
Anemia
Weight loss
what is stage 1-2 PC
confined to prostate
what is stage 3 PC
large tumor or extraprostatic tumor possible invading adjacent structures
how is prostate cancer graded?
based on histologic appearance with the gleason and grade score
what is the gleason score
2 scores from 2 samples added together
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
