Prostate Cancer Therapeutics Flashcards
what is the etiology of prostate cancer
testosterone is a growth signal to the prostate
what are risk factors for prostate cancer
-increased age
-african american
-family history
signs and symptoms of prostate cancer
-asymptomatic in early disease
-alterations in urinary habits
-impotence
-lower extremity edema
-weight loss
-anemia
what describes the natural progression of prostate cancer?
-indolent slow growing disease
-spreads by local extension via lymphs or hematogenously
-metasis to the bone, lung, liver
How to diagnose prostate cancer
-physical exam
-PSA level
-ultrasound
-biopsy of the prostate
what is used to grade prostate cancer
Gleason Score (2-10)
what is a gleason score of 2-4
slow-growing, well differentiated
what is a gleason score of 8-10
aggressive, poorly differentiated
what does a higher gleason score indicate
higher score, higher the risk of extracapsular spread
what is a normal PSA score
04
what PSA score requires evaluation
> 4
what PSA score is highly suspicious for Malignancy
> 10
what PSA velocity is suspicious for malignacy
> 0.75
how is treatment determined for prostate cancer
-stage
-grade of disease (gleason score)
-age of patient
-health status
-personal preference
when to use localized therapy in prostate cancer
Early stage
what is m1
metastatic, found on scans
what is m0
non metastatic (PSA only)
what is HSPC
hormone sensitive prostate cancer
what is CRPC
castrate resistant prostate cancer
what are 3 localized treatment options for prostate cancer
observation, active surveillance, radiation
what is localized observation therapy
-monitoring course of disease w/ expectation to deliver palliative therapy
what labs do you get and how frequently for localized observation therapy
-PSA and DRE every 6 months
what are the advantages and disadvantages for localized observational therapy
advantage: avoids immediate morbidity associated with treatment
disadvantage: risk of disease complications such as urinary retention or fractures
what is localized active surveillance
watch and wait then treat if disease progresses
what are the advantages and disadvantages to localized active surveillance
advantages: ~2/3 of patients eligible for surveillance will avoid therapy. QOL less affected
disadvantages: 1/3 of patients may require treatment. follow-up and tests may be necessary
what are the pros and cons of localized radiation therapy
-equivalent with surgery and good alternative with those who are not surgical candidates
-complications include: bladder or rectal symptoms, ED
-can add adjuvant ADT if intermediate or poor risk
when to use radical prostatectomy + PLND
-curative therapy
-men with > 10 years life expectancy due to perioperative morbidity
what should radical prostatectomy be followed with
Adjuvant ADT therapy if lymph node positive/high risk recurrence
what is the goal of ADT
goal is to include castrate levels of testosterone
what drug classes can be used for ADT
-LHRH agonist +/- anti-androgen or orchiectomy
-Antiandrogens
What are the options for LHRH agonists for ADT
-leuprolide
-Eligard
-Goserelin
-Triptorelin
-Histerelin
what are toxicities of LHRH agonists
-Acute: tumor flare, ED
-Long term: osteoporosis, fracture, obesity, increased risk for CVE
what are the anti-androgens
Flutamide
Bicalutamide
Nilutamide
when to start anti-androgens and how long should they be on them?
-start 1 week prior to LHRH agonists
-continue for duration of therapy
what is the first line for metastatic disease
palliation of disease
suppress the testosterone production
treatment of m0HSPC
psa doubling time < 6 months: can give ADT
psa doubling time > 6 months can observe
describe intermittent ADT in m0HSPC
start on LHRH agonist alone or with oral ADT
d/c androgren suppression when PSA drops below 4
can start and stop w/o being an issue
what is the advantage of ADT in m0HSPC
decreased cost and side effects
what is m0CRPC
psa still increasing and not responding to ADT but no distant metastasis
treatment path for m0CRPC
continue ADT
add on either enzalutamide, apalutamide, darolutamide
what is are contraindication for enzalutamide use
history of seizures
lots of CYP DDIs
dont have to take w/ prednisone
what are toxicities for enzalutamide
fatigue
seizures
falls
weakness
foggy brain (big one)
who should caution use with apalutamide
pts w/ history of seizures, QT prolongation, falls, and thyroid dysfunction
compare the toxicities of darolutamide w/ other anti-androgen receptors
less toxicities and less severe toxicities
less fractures, falls, seizures, weight loss
what is m1HSPC
patient now has visceral metastases
hormone sensitive disease
what are the two categories of m1HSPC
low volume (fewer mets)
high volume (more mets)
what is the treatment path for low volume m1HSPC
LHRH agonists or LHRH antagonists and add any of the following:
abiraterone + prednisone
enzalutamide
apalutamide
what drug must be given with prednisone and why
abiraterone must be given with prednisone to help prevent adrenal insufficiency
what is the treatment path for high volume m1HSPC
LHRH agonists or LHRH antagonists and add any of the following:
abiraterone + prednisone
enzalutamide
apalutamide
now chemo is an option
what is the 1st line chemo regimen for m1HSPC
docetaxel + ADT
what is the 1st line chemo regimen in M1CRPC
docetaxel + ADT + abiraterone/darolutamide
what are PSA range categories
0-4 normal
>4 requires evaluation
>10 highly suspicious for malinancy
what are the ACS guidelines for prostate screening in men
50 and up should have annual screening if PSA is >= 2.5 or every 2 years if PSA<2.5
what group of men should start screening early and at what age
Black men w/ first degree relative of cancer screening at 45
40 yom w/ 1st degree relative of early prostate cancer
