Therapeutics of Prostate Cancer (Weddle) Flashcards by Sydney Jablonski

_________ is a growth signal to the prostate.

testosterone

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_______ is a key enzyme involved in the biosynthesis of testosterone.

CYP17A1

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Prostate cancer is more common in ___________, and less common in _________.

African Americans; Asians

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List the two screening modalities for prostate cancer.

digital rectal exam (DRE) and prostate specific antigen (PSA)

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What PSA level requires evaluation?

> 4 ng/mL

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What PSA level is highly suspicious for malignancy?

> 10 ng/mL

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What PSA velocity is suspicious for malignancy?

> 0.75 ng/mL rise per year

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What factors can decrease PSA levels?

finasteride and dutasteride

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What factors can increase PSA levels?

ejaculation, prostatic manipulation/biopsy, BPH, prostatitis

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When would someone receive a transrectal ultrasound?

as a follow-up after abnormal PSA or DRE

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How often should men 50+ get screened for prostate cancer if they have a PSA of 2.5 OR higher?

annually

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How often should men 50+ get screened for prostate cancer if their PSA is < 2.5?

every 2 years

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At what age should high-risk men be screened for prostate cancer?

45 (typically)

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What was the PCPT Trial?

studied finasteride for prostate cancer prevention

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During the PCPT Trial, patients on finasteride that developed prostate cancer had disease with a(n) ___________ Gleason score

increased

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What is the REDUCE Trial currently evaluating?

dutasteride for prostate cancer prevention

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True or false: finasteride and dutasteride are approved for prostate cancer prevention.

false

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What did the SELECT Trial assess?

if selenium and vitamin E decrease the incidence of prostate cancer in healthy men

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What are some signs and symptoms of advanced prostate cancer?

alterations in urinary habits
impotence
lower extremity edema
weight loss
anemia

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The most common site of metastasis for prostate cancer is ______.

bone

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Most prostate cancers are _____________.

adenocarcinomas (99%)

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What range of Gleason scores indicates that a tumor is slow-growing and well-differentiated?

2-4

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What range of Gleason scores indicates that a tumor is aggressive and poorly-differentiated?

8-10

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What does m1 mean?

metastatic

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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.

1. bicalutamide 2. nilutamide 3. flutamide 4. abiraterone 5. 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?

1. ADT (LHRH agonists) 2. 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+?

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

Therapeutics of Prostate Cancer (Weddle) Flashcards

(80 cards)