Term
| signs and symptoms of prostate cancer |
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Definition
early prostate cancer has no symptoms
advanced cancer:
weak or interrupted urine flow
problems with urination, frequency, hesitation, blood in the urine
impotence
weight loss
anemia
metastatic cancer:
spread to the bones, especially hips, spine, ribs, or other areas
can cause significant pain |
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Term
| prostate cancer risk factors |
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Definition
age
race:
AA > Caucasian > Asian
family history
occupation
diet
obesity |
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Term
| prostate cancer screening |
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Definition
controversial
starting at age 50 with men at normal risk
even earlier for men at high risk
high false positives: may identify tumors that will not threaten the health of the patient
digital rectal exam
prostate specific antigen
transrectal ultrasound
follow up to DRE and PSA |
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Term
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Definition
irregular or firm areas
hard, knobby vs. smooth and rubbery for BPH
cons:
low sensitivity
observer bias
pros:
cancer found usually > 85% of the time
prostate cancer usually develops in a palpable area via rectal exam
inexpensive exam
relatively invasive when compared to other procedures |
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Term
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Definition
physiologic role: liquefying the seminal fluid
stimulates growth in the prostate
normal 0-3 ng/mL
wide range, dependent on many factors
men > 50 should consider DRE/PSA screening
if PSA > 0.6 ng/mL annual screening recommended
also used in monitoring patients with prostate cancer
predictor of response to therapy
only moderately associated with survival
beneficial in diagnosis
cut off point varies depending on what source is used; sensitivity/specificity problems
fairly cheap test, non-invasive, and is quick
cons:
PSA is not cancer specific!
level may be misinterpreted |
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Term
| transrectal ultrasonography (TRUS) |
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Definition
used for imaging
helps guide needle biopsy of the prostate
not specific enough for diagnostic purposes
hypoechoic areas are commonly associated with cancers |
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Term
| prevention of prostate cancer |
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Definition
NOT vitamin E
selenium
diet high in lycopene
weight loss
finasteride vs. dutasteride |
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Term
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Definition
selenium and vitamin E taken separately or together
original study showed no benefit form the use of either product alone or in combination
new findings may put a patient at an INCREASED RISK OF CANCER |
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Term
| 5 alpha reductase inhibitor |
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Definition
finasteride, dutasteride
blocks the action of the 5 alpha reductase enzymes
this is crucial for the conversion of testosterone into dihydrotestosterone (DHT)
ADRs:
common - decreased libido, impotence, depression
rare - breast tenderness, allergic reactions
use as prophylaxis:
24.8% reduction in prostate cancer but the men who got prostate cancer with this prophylaxis had extremely aggressive cancer
DO NOT RECOMMEND FOR CANCER PROPHYLAXIS |
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Term
| prostate cancer diagnosis |
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Definition
physical exam
PSA: cancer marker, but also used in monitoring response
TRUS
transrectal biopsy or transurethral resection of the prostate (TURP)
requires 2 biopsies to confirm diagnosis
bone scan: mets to bone most common; also to the liver and lung |
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Term
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Definition
| Gleason grade: 2-10 based on growth and differentiation (8-10 = very fast growth) |
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Term
| treatment: localized disease (stage I and II) |
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Definition
multiple factors must be weighted: Gleason score and patient characteristics, not all patients require treatment
treatment options (or in combination):
watchful waiting
radical prostatectomy
radiation therapy
androgen ablation |
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Term
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Definition
most appropriate for elderly patients with a low stage/grade
regular physical evaluations and labs
advantages: avoids unnecessary treatments, risks, and morbidity to the patient
disadvantages: you may be wrong with life expectancy, later course of disease may not respond as well |
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Term
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Definition
curative therapy for early stage disease
high risk of complications:
therefore, many choose to postpone therapy
impotence (reduced with nerve sparing surgery)
incontinence
bladder complications
mortality (very low risk) |
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Term
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Definition
types:
external beam radiation
internal beam radiation (brachytherapy)
options for patients that have low risks of recurrence or cannot tolerate surgery
still significant risks: impotence, bladder/rectal complications
ADRs:
impotence
bladder and bowel complications
incontinence
acute cystitis |
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Term
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Definition
| outside the body focused radiation |
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Term
| brachytherapy (internal beam) |
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Definition
permanent implantation of radioactive beads
best for patients who have a low risk for recurrent cancer |
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Term
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Definition
types:
orchiectomy
LHRH agonists
use:
not able to have surgery or radiation
surgery or radiation therapy failure
(+) radiation therapy as initial treatment
metastatic disease |
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Term
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Definition
removal of the testes
pros: rapidly reduces circulating androgens
preferred initial treatment in patients with spinal cord suppression or urethral obstruction |
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Term
| androgen ablation: LHRH agonists |
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Definition
LHRH: leuprolide, gosrelin, triptoerelin
given with or without antiandrogen therapy or is an alternative to orchiectomy
reversible treatment
goal testosterone level < 20 ng/dL after 1 month
all 3 appear to be relatively equally effective to each other and similar to orchiectomy
leuprolide:
SQ q3-12 months
IM q1-4 months
implant q12 months
implant can be removed if the ADRs are not tolerable
ADRs:
disease flare
injection site reaction
hot flashes
impotence
decreased libido
goserelin:
implant q1-3 months
triptorelin:
IM q1-3 months |
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Term
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Definition
non-steroidal anti-androgen
mechanism of action: inhibits androgen uptake and binding in target tissues
flutamide, bicalutamide, nilutamide
similar efficacy between the agents
used alone or in combination with LHRH agonists (combined androgen blockade (CAB))
combination therapy especially for advanced prostate cancer
can decrease tumor flare
pure antiandrogens bind to the androgen receptor in the prostate and the hypothalamus
eliminates the negative feedback loop of testosterone on the release of LH
leads to a dramatic increase in testosterone and estrogen levels
therefore it is best used in combination with either and LHRH or orchiectomy
treatment will block the effects of rising testosterone levels, but the effect of rising estrogen levels will remain unopposed
lead to feminizing effects
most notably gynecomastia
objective response: decrease in bone pain, decrease in prostate size, decrease in PSA levels
ADRs:
diarrhea and hematuria
gynecomastia
hot flashes
LIVER FUNCTION TEST ABNORMALITIES; LFTs will rise in more than 50% of patients |
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Term
| combined androgen blockade (CAB) |
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Definition
majority of patients respond to LHRH agonists or orchiectomy
however, many patients will relapse
goal is to interfere with multiple hormonal pathways to completely eliminate androgen action
antiandrogens used in combination with LHRH agonist or surgical castration can help decrease elevation of estrogen and testosterone levels
interferes with multiple pathways
both testosterone and estrogen are essential for normal bone metabolism
reducing the anabolic bone effects of both androgens will increase bone loss and promote osteoporosis |
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Term
| treatment of locally advanced prostate cancer: stage C (III) |
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Definition
watchful waiting
adrogen ablation for 2-3 years
radiation with or without androgen ablation
CAB often used for 2-3 months before radiation, then continued for 6 months after
radical prostatectomy with or without androgen ablation |
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Term
| treatment of metastatic disease: stage D (IV) |
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Definition
androgen ablation
antiandrogen before LHRH agonist
slight survival benefit with CAB
palliative radiation therapy |
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Term
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Definition
urinary problems
prostatectomy > radiotherapy
erectile dysfunction
prostatectomy > radiotherapy > hormonal
bowel dysfunction
radiotherapy > prostatectomy
bone loss
andorgen deprivation therapy |
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Term
| hormone refractory tumors |
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Definition
failed 2 hormonal therapies
continued tumor growth despite testosterone levels < 50 ng/mL
patients may have lost response to traditional anti hormonal therapy
chemotherapy and immunotherapy:
sipuleucel-T
docetaxel
cabazitaxel
abiraterone |
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Term
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Definition
immunotherapy: for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer
cancer vaccine: dendritic cell based vaccine targeting tumor antigens
administration: 3 dose cycles separated by 2 weeks; premedicate patients with diphenhydramine and APAP
con: cost - extremely expensive (~$90,000)
cell collection center - leukapheresis to collect patient APCs
Provenge manufacturing center - APCs exposed to prostate cancer antigen
infusion center - patient administered activated APCs
ADRs:
infusion reactions most commone
back pain
nausea
joint aches
fatigue |
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Term
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Definition
for cancer which has spread beyond the prostate; failed hormone therapy
use: shrink tumor, slow tumor growth, reduce pain
options: docetaxel, cabizataxel |
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Term
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Definition
MOA: binds to microtubules reversibly, stabilizing microtubules and prevents polymerization
docetaxel + prednisone
ADRs:
alopecia
bone marrow suppression
neutropenia
thrombocytopenia
N/V/D
infusion site reactions |
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Term
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Definition
indication: castrate resistant prostate cancer
MOA:
is an androgen biosynthesis inhibitor that directly affects the androgen biosynthesis pathway
inhibits CYP17 (17 alpha-hydroxylase)
androgen biosynthesis is inhibited at 3 sources of testosterone production: testes, adrenal glands, and prostate tumor tissue
abiraterone + prednisone
TAKE ON AN EMPTY STOMACH
ARDs:
toxicity when taken with food
joint swelling
hypokalemia
edema
muscle discomfort
hot flushes
serious ADRs:
mineralocorticoid excess
cardiac adverse reactions
liver toxicity |
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Term
| chemotherapy - cabazitaxel |
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Definition
taxane antineoplastic
promotes microtubule formation and prevents disassembly, leading to a frozen microtubule state
another option other than docetaxel
potential benefits over docetaxel:
poor binding to Pgp
can transport across the BBB
cabazitaxel + prednisone
ADRs:
hematologic, primarily neutroopenia
diarrhea
fatigue, N/V, hematuria
infusion reactions
BBW for neutropenic death
docetaxel DOES NOT cause neutropenia <- IMPORTANT DISTINCTION BETWEEN THE 2 DRUGS |
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Term
| treatment of bone metastasis |
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Definition
bisphosphonates: pamidronate, zoledronic acid
helps decrease fractures and relieve bone pain in patients who have advanced cancer
inhibits tumor induced osteoclast mediated bone resorption
ADRs: abdominal pain, nausea, diarrhea, flu like symptoms
denosumab: monoclonal antibody
MOA:
pre-osteoclasts express a receptor on their surfaces called RANK
RANK is activated by RANKL, which is produced by osteoblasts
denosumab inhibits this maturation of osteoclasts by binding to and inhibiting RANKL
ADRs: constipation, urinary and respiratory tract infections, joint pain |
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