Therapeutics of Prostate Cancer (Weddle) Flashcards
_________ is a growth signal to the prostate.
testosterone
_______ is a key enzyme involved in the biosynthesis of testosterone.
CYP17A1
Prostate cancer is more common in ___________, and less common in _________.
African Americans; Asians
List the two screening modalities for prostate cancer.
digital rectal exam (DRE) and prostate specific antigen (PSA)
What PSA level requires evaluation?
> 4 ng/mL
What PSA level is highly suspicious for malignancy?
> 10 ng/mL
What PSA velocity is suspicious for malignancy?
> 0.75 ng/mL rise per year
What factors can decrease PSA levels?
finasteride and dutasteride
What factors can increase PSA levels?
ejaculation, prostatic manipulation/biopsy, BPH, prostatitis
When would someone receive a transrectal ultrasound?
as a follow-up after abnormal PSA or DRE
How often should men 50+ get screened for prostate cancer if they have a PSA of 2.5 OR higher?
annually
How often should men 50+ get screened for prostate cancer if their PSA is < 2.5?
every 2 years
At what age should high-risk men be screened for prostate cancer?
45 (typically)
What was the PCPT Trial?
studied finasteride for prostate cancer prevention
During the PCPT Trial, patients on finasteride that developed prostate cancer had disease with a(n) ___________ Gleason score
increased
What is the REDUCE Trial currently evaluating?
dutasteride for prostate cancer prevention
True or false: finasteride and dutasteride are approved for prostate cancer prevention.
false
What did the SELECT Trial assess?
if selenium and vitamin E decrease the incidence of prostate cancer in healthy men
What are some signs and symptoms of advanced prostate cancer?
- alterations in urinary habits
- impotence
- lower extremity edema
- weight loss
- anemia
The most common site of metastasis for prostate cancer is ______.
bone
Most prostate cancers are _____________.
adenocarcinomas (99%)
What range of Gleason scores indicates that a tumor is slow-growing and well-differentiated?
2-4
What range of Gleason scores indicates that a tumor is aggressive and poorly-differentiated?
8-10
What does m1 mean?
metastatic
What does m0 mean?
non-metastatic (PSA only)
What does HSPC mean?
hormone sensitive prostate cancer
What does CRPC mean?
castrate resistant prostate cancer
Give 1 advantage and 1 disadvantage of observation for localized prostate cancer.
- advantage: avoids immediate morbidity associated with treatment
- disadvantage: risk of disease complications such as urinary retention or fractures
Give three advantages of active surveillance of prostate cancer.
- ⅔ of patients eligible for surveillance will avoid therapy
- avoid possible side effects
- QOL less affected
Give two disadvantages of active surveillance for localized prostate cancer.
- ⅓ of patients may require treatment
- periodic follow-up and tests/biopsies may be necessary
Can you radiate localized prostate cancer?
reasonable alternative to patients who aren’t surgical candidates
What is the definitive, curative therapy for localized prostate cancer?
radical prostatectomy + PLND
Due to its perioperative morbidity, radical prostatectomy + PLND should really only be used in men with ______ years life expectancy.
> 10 years
What is the goal level of testosterone after 1 month of ADT?
< 50 ng/dL
Give 1 surgical and 1 medicinal method of ADT.
surgical: ochiectomy
medicinal: LHRH agonists
List 5 antiandrogen drugs.
- bicalutamide
- nilutamide
- flutamide
- abiraterone
- enzalutamide
What is the goal of therapy for metastatic prostate cancer?
palliation of disease
When would you consider ADT in m0HSPC prostate cancer?
if rapid PSA velocity or short PSA doubling time + long life expectancy
You can give ADT in m0HSPC prostate cancer if PSA doubling time is _________.
< 6 months
What are the two major toxicities of anti-androgen therapy?
impotence and hot flashes
LHRH agonists are just as effective as orchiectomies, with the added bonus of being _________.
reversible
Give four examples of LHRH agonists that can be used for metastatic prostate cancer.
leuprolide, goserelin, triptorelin, histerelin
Which LHRH agonist is administered as a SQ implant?
histerelin
Give some acute toxicities associated with LHRH agonists.
tumor flare, gynecomastia, hot flashes, ED, edema, injection site reaction
Give some long-term toxicities associated with LHRH agonists.
osteoporosis, fracture, obesity, insulin resistance, lipid changes, increased risk of diabetic and cardiovascular events
What four levels will increase with long-term LHRH use?
fat mass, plasma insulin, cholesterol, TGs
Choice of LHRH agonist should be based on ________ and ______.
convenience; cost
How can we present disease flare with LHRH agonist use?
add an additional anti-androgen therapy short-term (7 days)
What agents make up combined androgen blockade (CAB)?
LHRH agonist + anti-androgen
True or false: CAB therapy offers maximal benefit over monotherapy.
false
When can you discontinue androgen suppression during m0HSPC?
When PSA returns to a pre-specified baseline
What are the two major benefits of intermittent ADT for m0HSPC prostate cancer?
decreased cost and decreased side effects
What would be a benefit of using an LHRH antagonist over an LHRH agonist?
faster drop in testosterone
Give an example of an LHRH antagonist that can be used in prostate cancer (not seen often though due to price)
degarelix
Utilizing an LHRH antagonist eliminates tumor flare and ultimately eliminates the need for ______.
ADT
What regimen would you recommend for m0CRPC prostate cancer?
- continue ADT (usually an LHRH agonist)
- add in either enzaluatmide, apalutamide, or darolutamide
True or false: abiraterone does not have an indication in the M0 setting.
true
Enzalutamide decreases serum concentrations of ________.
warfarin
Use enzalutamide with caution in patients with a history of ________.
seizures
Enzalutamide should NOT be given with ________.
prednisone
In what patient groups should you use apalutamide cautiously?
history of seizures, QT prolongation, falls, thyroid dysfunction
Which anti-androgen drug has 2 phaermacologically active diastereomers?
darolutamide
Darolutamide may be considered better than other agents in its class due to what?
less toxicities
At which prostate cancer stage does a patient now have visceral metastases?
m1HSPC
We will determine therapy for m1HSPC based on the _______ of the disease.
volume
If not previously performed, what tests should be run for m1HSPC prostate cancer?
MSI-H/dMMR and germline testing for gene mutations
What drug regimen would you recommend for low volume m1HSPC?
- ADT (LHRH agonists)
- continue ADT and add either: abiraterone + prednisole, enzalutamide, or apalutamide
Abiraterone selectively and irreversibly inhibits ________.
CYP17
What is the 1st line treatment for high volume m1HSPC?
docetaxel + ADT
In metastatic CRPC, all patients will eventually become _________.
hormone refractory
In addition to continuting ADT therapy, what other options could be considered for m1CRPC?
- docetaxel (chemo of choice)
- sipuleucel-T (only for asymptomatic without liver mets)
- cabazitaxel
- radium-223
- abiraterone + prednisone
- enzalutamide
- mitoxantrone
- genomic testing
Can sipuleucel T be used for patients with an ECOG score of 2+?
no
How does cabazitaxel differ from other taxanes?
poor affinity for MDR proteins, therefore conferring activity in resistant tumors
What regimen is approved 1st line for m1CRPC?
docetaxel + prednisone
What regimen is approved 2nd line for m1CRPC?
cabazitaxel + prednisone
Give some toxicities of radium-223.
anemia, neutropenia, thrombocytopenia
True or false: radium-223 can be used concurrently with chemotherapy.
false (due to toxicities)
What toxicity is associated with strontium?
myelosuppression
Can PARP inhibitors be used for prostate cancer?
yes; breakthrough therapy designation
What drug can be used for prostate cancer that has dMMR/MSI-H characteristics?
pembrolizumab