FINAL EXAM Flashcards
What are the risk factors for Prostate Cancer?
- Older Age
- African American
- Family History
What are the symptoms of Early Prostate Disease?
Asymptomatic
What are the symptoms of Late Prostate Disease?
- Frequent Urination
- Weak/Slow Urine Flow
- Dysuria
- Nocturia
- Hematospermia
- Erectile Dysfunction
What are the symptoms of Metastatic Prostate Disease?
- Back Pain
- Spinal Cord Compression
- Pathological Fracture
- Anemia
- Fatigue
- Weight Loss
What is the Goal of Prostate Cancer Screening?
Identify: High Risk - Localized Prostate Cancer that can be successfully treated, thereby preventing the morbidity/mortality
Screening and Early Detection of Prostate Cancer is most beneficial for men aged what?
55-69 yrs
What is the Diagnosis Test for Prostate Cancer?
PSA Test
Define PSA
- Total PSA
- Prostate specific antigen is a glycoprotein produced by both epithelial cells and cancer cells of the prostate gland
- Liquifies Seminal Secretions
PSA is specific to the prostate bu not specific for ____.
Cancer
T/F: A single PSA measurement is NOT diagnostic
True
T/F: A PSA Test is NOT a valuable tool to predict recurrence
False
What are factors that can INCREASE PSA?
- BPH
- Infections
- Prostatitis
- Age
- Prostatic Manipulation
How long should men abstain from ejaculation to prevent a false increased PSA?
48 hours
What are factors that can DECREASE PSA?
5-AIRS:
1. Finasteride
2. Dutasteride
Finatsteride and Dutasteride can cause a ____ decrease in PSA?
50%
Define PSA Velocity
Rate of Change in PSA over time
How do you determine a PSA Velocity?
3 Separate PSA values calculated over at least an 18 month period
How long does it take for PSA to Double: PSA Doubling Time?
< 10 months = progressing quickly
Define Percent Free PSA
% PSA is significantly lower in men who have prostate cancer
-Approved in men >50
If PSA is < ___%, Biopsy is recommended
25
Define PSA Density
Size of prostate gland measured by TRUS and divide PSA by prostate volume
Ideally PSA Density should be < ____ ng/ml/g
0.15
Large Prostates tend to have ____ PSA values
Higher
For Observation in Prostate Cancer, when is it preferred?
- Low Risk Patients AND
- Life Expectancy <10 years
How often do you monitor PSA in the Observation Treatment Modality?
Monitor PSA NOT more than every 6 months
Define the Active Surveillance Treatment Modality of Prostate Cancer
Monitor the course of disease with the intent to deliver potentially curative therapy upon progression of disease
When is Active Surveillance preferred in Prostate Cancer?
- Very Low Risk Disease AND
- Life Expectancy >20 years
OR - Low Risk Disease AND
- Life Expectancy >10 years
How often do you monitor PSA in Active Surveillance Treatment Modality
Monitor PSA NOT more than every 6 months unless clinically indicated
Surgery [Radical Prostatectomy +/- Pelvic Lymph Node Dissection] is a Treatment Modality in Prostate Cancer, but when is it appropriate?
Radical Prostatectomy RP is appropriate if the tumor is confined to prostate and is definitive curative therapy
When is Surgery [Radical Prostatectomy +/- Pelvic Lymph Node Dissection] Treatment Modality preferred in Prostate Cancer patients?
Life Expectancy 10 years and NO serious comorbid conditions
PSA should be UNDETECTABLE after Surgery [Radical Prostatectomy +/- Pelvic Lymph Node Dissection], if a persistent PSA is present, what does that indicate?
Inadequate Surgery or Metastases
Radiation +/-Adjuvant ADT is used when in Prostate Cancer?
- Early Stage HIGH RISK
- Early Stage Intermediate RISK
What is the Goal of Hormonal Therapy [Androgen Deprivation Therapy (ADT)]?
To achieve castrate levels of serum testosterone <50 ng/dL
What are the methods of ADT?
- Surgical Castration
- Chemical Castration
How is Chemical Castration ADT done?
- LNRH/GnRH Agonist +/-
- First Generation Antiandrogen (-tamide)
- LNRH Antagonist
What drugs are classified as LHRH Agonists?
- Goserelin – SubQ implant
- Leuprolide – IM
- Triptorelin
- Eligard – SubQ
What is the MOA of LHRH Agonists?
Paradoxical depletion of luteinizing hormone LH. Decreased LH release and testosterone production.
Synthetic LHRH Agonists have a ____ affinity to the receptor and _____ susceptibility.
Higher; Lower
How long does it take for LHRH Agonists to cause down regulation and castrate levels of testosterone?
3-4 weeks
What are AEs of LHRH Agonists?
- Hot Flashes
- Lethargy
- ED
What are the Latent Effects of LHRH Agonists?
- Bone Loss
- Fractures
- Metabolic Syndrome
- CV Disease
- Diabetes
- VTE
What drugs are classified as LHRH Antagonists?
- Degarelix – SubQ
- Relugolix – PO
What is the MOA of LHRH Antagonists?
Antagonists irreversibly bind to LHRH receptors on pituitary gland and reduce production of testosterone to castrate levels
Which LHRH class is associated with Tumor Flare?
Agonists
What are the AEs associated with LHRH Antagonists?
- Injection Site Problems
- MAJOR CV for Relugolix
What drugs are classified as Antiandrogens?
- Bicalutamide
- Flutamide
- Nilutamide
What is the FDA indication of Antiandrogens?
Used in conjunction with ADT
What is the place of therapy for Antiandrogens?
Prevent Flare Phenomenon in LHRH Agonists
For a patient with Unfavorable, Intermediate Risk in Prostate Cancer what is the recommended therapy regimen?
EBRT + ADT
For a patient with High Risk in Prostate Cancer what is the recommended therapy regimen?
EBRT + Neoadjuvant/Adjuvant/Concurrent ADT After Radiation
For a patient with Regional Disease N1,MO in Prostate Cancer what is the recommended therapy regimen?
- EBRT
- Abiraterone
- ADT
Define Castrate Sensitive
- Patients who have not been treated with ADT and those who are not an ADT at the time or progression.
- Patients have been neoadjuvent, adjuvant, or concurrent ADT as part of RT provided they have RECOVERED TESTICULAR FUNCTION.
Define Castration Resistant
Progression of disease despite castrate levels of testosterone <50 ng/mL
For Non-Metastatic Castration Sensitive Disease M0SPC what is recommended therapy for a patient with a shorter PSADT <10 months/Rapid PSA Velocity?
Consider ADT earlier rather than later
For Non-Metastatic Castration Sensitive Disease M0SPC what is recommended therapy for a patient with a longer PSADT >12 months/Older Age?
Candidate for observation
For Non-Metastatic Castrate Resistant Disease M0CRPC what is the recommended therapy for PSADT >10 months?
Continue ADT to maintain castrate level testosterone <50 ng/mL
For Non-Metastatic Castrate Resistant Disease M0CRPC what is the recommended therapy for PSADT <10 months?
Continue ADT + Aplatutamide or Enzalutamide or Darolutamide
What is the Dose of Enzalutamide?
160 mg PO QD without regard to food
What are the AEs of Enzalutamide?
- Falls
- Dizziness
- Insomnia
- Seizures
T/F: You can initiate Enzalutamide therapy in a patient with a history of seizures?
False
What are the DDIs of Enzalutamide?
CYP3A4 Inducer, interacts with DOACs
What is the dose for Apalutamide?
240 mg QD without regard to food
What are the AEs of Apalutamide?
- Maculopapular Rash
- Hypothyroidism
What are the DDIs of Apalutamide?
Strong CYP3A4 and CYP2C19 Inducer
What is the dose of Darolutamide?
600 mg BID to be taken WITH FOOD
Does Darolutamide need renal dose adjustment? If so, what is the CrCl cutoffs?
YES, Needed for CrCl <30 mL/min
Which “tamide” is associated with the least amount of DDIs and CNS side effects?
Darolutamide
What is the backbone therapy for Metastatic Hormone Sensitive Disease Prostate Cancer?
ADT
What therapy regimens are recommended in High Volume Metastatic Prostate Cancer?
- ADT + Docetaxel + Abiraterone + Prednisone OR
- ADT + Docetaxel + Darolutamide
Which High Volume Metastatic therapy regimen is better according to the STAMPEDE Trial?
ADT + Docetaxel + Abiraterone + Prednisone
What is the MOA of Abiraterone?
Blockade of CYP17 enzyme = reduction in serum cortisol = increase in ACTH
T/F: Abiraterone has to be given with a glucocorticoid agent: Prednisone.
True
What is the administration of Abiraterone?
Must be taken on an empty stomach
What are the AEs of Abiraterone?
- HTN
- Hypokalemia
- Fluid Retention – monitor monthly
When is use of Aniraterone cautioned?
Patients with a history of cardiovascular disease
If patients demonstrate progression of disease after ADT + Docetaxel therapy, what should be given based on the ENZAMET Trial?
Enzalutamide + ADT
What is the Standard of Care in Metastatic Prostate Cancer?
Triplet Therapy
1. ADT + Docetaxel + Abiraterone (+Prednisone)
2. ADT + Docetaxel + Darolutamide
T/F: In Metastatic Castrate Resistant Prostate Cancer CRPC, ADT is NOT continued.
FALSE - ADT is continued in the castrate resistant setting
What is approved for the pre-/post- Docetaxel setting for CRPC?
- Abiraterone
- Enzalutamide
Abiraterone + Predisone CANNOT be used in what patient population for CRPC?
Patients with VISCERAL Metastases
What is the MOA of Taxanes?
Anti-Microtubular
What 2 Taxanes have FDA indications for CRPC use?
- Docetaxel
- Cabaxitaxel
How should Docetaxel be given in CRPC?
Give with Prednisone
What are the AEs of Docetaxel?
- Peripheral Edema
- Myelosuppression
- Alopecia
- Peripheral Neuropathy
T/F: Docetaxel does NOT contain Cremphor and therefore, has a lower risk of hypersensitivity.
True
What is co-administered with Docetaxel to decrease Peripheral Edema?
Dexamethasone
What is the Contraindication of Docetaxel?
Severe Hepatic Impairment
If a patient does not respond to Docetaxel due to multi-drug resistance mechanisms, what should be used?
Cabaxitaxel
What is the specific indication of Cabazitaxel?
Metastatic hormone refractory prostate cancer only in patients who previously progressed on Docetaxel
How should Cabazitaxel be adminstered?
- Given with Prednisone
- Premedicate with H1 and H2 block and IV Corticosteroid 30 minutes prior to admin
Why do you have to premeditate with Cabazitaxel?
Polysorbate 80
What are the AEs of Cabazitaxel?
- Myelosuppresion
- Fatigue
- Hypersensitivity Rxns
What is the Indication of Sipuleucel-T?
Only indicated for asymptomatic or minimally symptomatic patients with no liver metastases, life expectancy > 6 months, and good performance status
What are the AEs of Sipuleucel-T?
- Chills
- Pyrexia
- Headaches
What is the premedication routine for Sipuleucel-T?
APAP 650 mg
Diphenhydramine 50 mg
What is the Indication for Radium 223 Xofigo?
Patients with metastatic CRPC with symptomatic bone only metastases, NO KNOWN Visceral metates before or after Docetaxel