Exam 2 lecture 4 (prostate) Flashcards by Matti Daniel

Describe the epidemiology of prostate cancer in men? (how common it is/ how many ppl it kills)

Most common malignancy in men
2nd most common cause of cancer related death in men

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pathogenesis of prostate cancer (What makes it worse)

hormonal
- testosterone is a growth signal for prostate
- most risk factors associated with prostate cancer is associated with increased exposure to testosterone
Androgen receptor
- alterations in androgen receptor

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Risk factors for prostate cancer

-Age (increased age)
-African American
- Family History
-(diet, longterm vasectomy, )

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Signs and symptoms of prostate cancer

asymptomatic with early disease

advanced disease
-alteration in urinary habits
- impotence
-lower extremity edema
- weight loss
- anemia

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Most common metastases of prostate cancer? How fast does prostate cancer spread?

Bone

Very slowly, most men will die of something else.

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diagnosis of prostate cancer

physical exam
PSA
transrectal ultrasound

bone scan/CT MRI if metastasis suspected

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How are prostate growths graded

Gleason score
Scores are assigned to the primary and secondary growth patterns and are added together.
(a score of 2-4 are slow growing and well differentiated,
a score of 8-10 are fast growing and poorly differentiated)

The higher the score, the higher the risk of extracapsular spread.

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What does PSA measure? Normal range? WHich ranges require evaluation?

PSAs measure seminal secretions. Value increases with disorders of prostate. Normal range= 0-4.

> 4, requires evaluation
10, highly suspicious for malignancy

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What are the treatment options for prostate cancer (depending on disease progression)

1.Localized therapy
2.Metastatic disease

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What are the different treatments of metastatic prostate cancers

M0 HSPC
Mo CRPC
M1 HSPC
-low volume
- high volume
M1 CRPC

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Define M0, M1, CRPC, HSPC

M1- metastatic, found on scans
M0- non- metastatic, PSA only
CRPC- Castrate resistant prostate cancer
HSPC- Hormone sensitive prostate cancer

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What are the different courses of treatment for LOCALIZED prostate cancer?

observation
active surveillance
Radiation therapy
surgery

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What are the definitions, pros and cons of active surveillance therapy for localized prostate cancer

active surveillance- Based on premise that cancer is benign. If cancer is noted to progress will initiate potentially curative therapy. Monitor PSA, DRE symptoms.
Advantages- 2/3rds of patients eligible for surveillance will avoid therapy
- avoid possible side effects
- QOL less affected
disadvantages- Periodic follow up tests/biopsies needed

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What is a reasonable alternative for patients that do not want to get surgery for localized prostate cancer? What are the complications that could arise from it? What should be adjuvant with this therapy?

Radiation therapy is a viable alternative.

Complications- bladder/rectal symptoms erectile dysfunction.

ADT (androgen deprivation therapy) and ebrt (external beam radiation therapy) can be combined

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What is PLND? What are the complications that could arise from it? What type of prostate cancer does it treat?

PLND (pelvic lymph node dissection) is a procedure used with radical prostatectomy. It is a definitive curative therapy that has an 85% curative rate within 10 years.

complications include incontinence, bladder contracture, impotence

treats localized prostate cancer

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What is ADT? What are the goal levels? What are the drugs used?

Goal is to induce castrate levels of testosterone.
goal level <50 after 1 month

LHRH agonist + anti androgen or orchiectomy

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What do anti androgens do? what are antiandrogen drugs?

Blocks androgen receptors and inhibits androgen uptake.

-tamide drugs are antiandrogens
(Enzalutamide, bicalutamide, nilutamide, flutamide) and abiraterone

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What are LHRH agonist drugs

Leuprolide, goserelin, triptorelin

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toxicities of LHRH agonist

acute- tumor flare, gynecomastia, hot flashes, erectile dysfunction, edema, injection site rxn

long term- osteoporosis, fracture, obesity, insulin resistance, changes in lipid, increased risk of diabetes and CV events

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LHRH agonist alternative is patient has cardiac dysfunction

Relugolix

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toxicity of the antiandrogens

the flutamides

diarrhea and hematuria

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What are the different tretaments of metastatic disease (prostate)

M0 HSPC
M0 CRPC
m HSPC (Low volume, high volume)
mCRPC

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What are some general principles of metastatic prostate cancer to create first line tx? What is goal of therapy?

Goal of therapy- palliation of disease, suppress test <50,

Need to determine whether this is PSA or overt metastatic disease
determine PSA doubling time

Course of tx depending on doubling time of PSA

PSA doubling time >6 months- observe
PSA doubling time < 6 months- give ADT

What are the tx of m0 HSPC

1. orchiectomy (removal of testes) leads to impotence and hot flashes 2. LHRH agonist 3. intermittent ADT

What is a risk of taking LHRH agonists

Risk of disease flare in first weeks of therapy due to initial release of testosterone

How to avoid flare when taking LHRH agonists

Add anti androgen agent short term

what are symptoms of flare reaction? why?

Bone pain or increased urinary symptoms Probably due to initial induction of LH and FSH by the LHRH agonist

WHen do we consider intermittent ADT for m0 HSPC? How to take it? advantages? What to monitor?

Men with biochemical failure only could consider intermittent therapy We can start LHRH agonist alone or with oral ADT advantage- decreased cost and decreased side effects PSA is monitored while patient is off therapy and androgen ablation is restarted at pre defined PSA

If we are treating Mo HSPC and PSA is still increasing and not responding to ADT and no distant metastasis found on scans, what should we consider

m0 CRPC

Drug regimen to do if PSA is still increasing and not respondong to ADT and no distant metastasis found (M0 CRPC)

Continue ADT (usually LHRH agonist) add on one of the follwoing -enzalutamide -Apalutamide -darolutamide

Which CRPC drug has no indication in M0 setting

Abiraterone

How does enzalutamide work? drug interactions (which CYPS) How does it affect warfarin What type of patients to be cautious in?

1. Works by blocking androgen binding and translocation of androgen receptor 2. Drug interactions- avoid CYP2C9 inhibitors 3. decreases serum concentrations of warfarin 4. caution in pts with seizure history treats m0 CRPC

What type of drug is apalutamide? How does it work? drug i/a? When to be cautious?

1. it is a non steroidal androgen receptor inhibitor 2. results in decreased proliferation of tumor cells and increased apoptosis 3. drug interactions- CYP3A4 and CYP2C9 4. Caution in pts with history of seizures, QT prolongation and falls

What type of drug is darolutamide? drug interaction? How does it differ from apalutamide and enzalutamide?

Structurally unique androgen receptor offers potentially less toxicities and less severe toxicities mainly metabolized through CYP3A4

why is darolutamide special? What does it decreases chances of? which anti androgen has the most toxicity

key advrese effects known to be increased with androgen receptor inhibitors were less with darolutamide. less fractures, falls, seizures, weight loss enzalutamide has most side effects (be careful with seizure histrory and warfarin with this drug)

Most commonly used LHRH anti androgen

bicalutamide

What is it called when patent has visceral metastases in scans that are hormone sensitive? How is therapy determined?

m1 HSPC determine therapy based on volume of disease (low volume, high volume)

what are tests performed for m1 HSPC

tumor testing for MSI-H or dMMR Germline testing for gene mutations

how to treat low volume m1 HSPC

1. ADT: LHRH agonists or LHRH antagonist 2: COntinue ADT and add any of the following 1. abiraterone+prednisone 2. Enzalutamide 3. APalutamide

How does abiraterone acetate work? What is it given with? What CYP does it inhibit?

Inhibits testosterone formation Inhibits formation of testpsterone precursors must be given with prednisone (to prevent adrenal insufficiency)

common toxicities of abiraterone? What is it a major substrate for?

HTN, edema, increased triglycerides and increased LFTs, liver toxicities , a fib, muscle aches common substrate for CYP3A4

how to treat high volume M1 HSPC? How does it differ from low volume

same therapies as low volume ADT+abiraterone+prednisone ADT+ enzalutamide ADT+ apalutamide Now chemotherapy becomes an option

1st line tx for m1 HSPC high volume

Docetaxel+ ADT (combination chemo + ADT) docetaxel is drug of choice for combo chemo for high volume

which are the category 1 recommendations for 1st line m1 disease high volume

ADT + docetaxel + Abiraterone ADT + docetaxel + Darolutamide

What does M1 CRPC mean? median survival?

metastatic castrate recurrent prostate cancer 6 months median survival

how to treat m1 CRPC

in addition to continuing ADT therapy, patient could do any of the followung sipuleucel-T docetaxel (alone or in combo with abiraterone and darolutamide) Cabazitaxel Radium-223 for bone metastases abiraterone+prednisolone Enzalutamide genomic testing :BRCA (olaparib), dMMR/MSI-H pembrolizumab

why is cabazitaxel second line therapy in m1 CRPC

reduces risk of neutropenia while not compromising efficacy

approved 1st line for m1 CRPC? 2nd line if they fail 1st line)

1st line- Docetaxel + prednisone 2nd- cabazitaxel + prednisone

what drug do we use for M1 crpc having bone metastases and no known visceral metastatic disease? Can we give with chemo?

Radium 223 dichloride never give with chemo

what drug is approved for M1 CRPC with dMMR/MSI-H characteristics

pembrolizumab

what are the different ways we screen for prostate cancer? How does each work? What is indicated for abnormal PSA or DRE

digital rectal exam (DRE)- normal prostate as consistency of tip of nose. Presence of lumos needs evaluation. Prostate specific antigen (PSA)- normal PSA- 0-4, >4 requires evaluation, >10 highly suspicious for malignancy transrectal ultrasonography (TRUS) indicated for abnormal PSA or DRE

Describe screening guidelines for prostate cancer

Men 50 and above- annual screening if PSA is greater than 2.5 men 50 and above- every 2 years if PSA < 2.5

what is an agent that might be used for prostate cancer prevention? What happens to patients of this drug that developed prostate cancer

Finasteride Patients on finasteride that developed prostate cancer had disease with an increased gleason score

summarize the treatment options for prostate cancer

1. localized- Active surveillance, radiation therapy, Surgery 2. M0 HSPC- Observation, ADT 3. M0 CRPC- ADT + Enzalutamide or apalutamide or darolutamide 4. M1 HSPC low volume- a) ADT b) ADT + enzalutamide or abiraterone or apalutamide c) sipuleucel T High volume- a) ADT b) ADT + Abiraterone or enzalutamide c) ADT + Docetaxel + abiraterone or darolutamide 5. M1CRPC- Genomic testing, DMMR, MSI status ADT with Docetaxel carbazitaxel radium 223 abiraterone enzalutamide sipuleucel T