38 – Prostate Cancer – Flashcards
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Describe the pathophysiology of *Prostate*
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- Accessory male sex organ - Between bladder and urogenital diaphragm - Controlled by androgens procuced by tests and adrenal gland - Produces alkaline secretions to help with fertilization
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>95% of prostate cancer cases are ____________.
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Adenocarcinoma
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True or false: Prostate cancer is the leading cause of cancer-related death in males
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False! Second leading cause Most frequent cancer seen in American men
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At what age do you normally see cases of prostate cancer and at what age do you see death?
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- New cases seen around the ages of 55-74 - Deaths occur from 75 to >84
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Which race has the highest incidence of prostate cancer?
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Black Followed by non-hispanic and whites
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What are the risk factors for prostate cancer?
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- *Age*: men >65 y/o - *Race*: increase incidence in african americans b/c of higher testosterone and decrease rate in asian due to decreased levels of 5-alpha-reductase - *Family history*: 2x risk if brother or father diagnosed
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What are the signs and symptoms of *early* prostate cancer?
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Asymptomatic
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What are the signs and symptoms of *late* prostate cancer?
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- Alterations in micturition - Anemia - Impotence - Lower extremity edema - Weight loss
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Describe the physical presentation of prostate cancer
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- Asymptomatic - Blood in urine or semen - Difficulty starting urination/weak flow - Impotence - Need to urinate frequently (especially at night) - Painful/burning urination - Painful ejaculation - Stiffness/pain in lower back, hips, and upper thighs
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Describe the disease course of prostate cancer
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- Indolent growth in early disease - Spreads via local extension: lymphatics, regional lymph, hematogenously - Metastasis to bone (most common), liver, or lung
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What are some risks of screening patients for prostate cancer?
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- Adverse effects from treatment - Associated with over-treatment - Potential to over diagnose
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Describe the *Prostate specific antigen*
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- Glycoprotein excreted by epithelial cells - Increased in situations like cancer, ejaculation prostate cancer, BPH - Specific to prostate but not specific for cancer - No threshold that effectively discriminates between cancer and non-cancer
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Describe the *Digital Rectal Exam*
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- Normal prostate has consistency like tip of nose - Lumps, hardness, inability to move prostate = further evaluation - Only less than half of masses are cancers
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What is the age to begin screening an average risk patient?
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- American cancer society: 50 - NCCN and AUA: 40
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What is the age to begin screening an high risk patient?
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- ACN: 40-45 - NCCN and AUA: 40
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Describe *5-alpha reductase inhibitors*
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- Agents: Dutasteride, Finasteride - MOA: inhibits conversion of testosterone to DHT which is involved in prostate epithelial proliferation - Can falsely lower PSA by 50%
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What are the adverse effects of *5-alpha reductase inhibitors*?
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- Decreased libido - Erectile dysfunction - Gynecomastia
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Describe the place in therapy of *5-alpha reductase inhibitors*
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Benefit symptomatic men with PSA < 3.0 ng/mL who are regularly screened with PSA for early detection of prostate cancer
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True or false Dutasteride is FDA approved for preventing or reducing risk of prostate cancer
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False Neither Finasteride or Dutasteride is FDA approved
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True or false: There are no recommendations for chemoprevention of prostate cancer
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True!
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At what PSA levels would you consider doing a prostate biopsy?
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2.5-4 ng/mL
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At what PSA levels is the traditional threshold for prostate biopsy?
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> 4 ng/mL
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At what PSA levels would you definitely obtain a prostate biopsy?
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> 10 ng/mL
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What is the *Gleason Score*?
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- Scale 1 (well differentiated) to 5 (poorly differentiated) - Take 2 different specimen scores and add them together = Gleason Score
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Describe the different *Gleason Scores*?
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- 2-4: slow growing, well differentiated - 5-7: intermediate - 8-10: aggressive, poorly differentiated - Higher score: extracapsular spread
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What are the three common treatment modalities for *localized prostate cancer*?
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- Active surveillance (if benign and indolent) - Radiation therapy - Surgery: radical prostatectomy
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What are the advantages of *Active surveillance*?
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- Avoid immediate morbidity associated with treatment - Avoid unnecessary treatment - Maintain QOL
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What are the disadvantages of *Active surveillance*?
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- Increased anxiety - Frequent med exams and biopsies - Risk of progression - Subsequent treatment may be more intense
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True or false: Surgery can result in more survival benefit than Radiation
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False! Equivalent
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What are some complications of *Radiation therapy*?
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- Impotence - Rectal/bladder symptoms
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What are some complications of *Radical prostatectomy + Pelvic lymph node dissection*?
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- Bladder contracture - Incontinence - Impotence
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What is the primary therapy for *intermediate risk prostate cancer*?
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- Androgen Deprivation Therapy - Goal: Serum testosterone < 20 ng/dL 1 month after initiation of therapy - Two types: Orchiectomy vs pharmacologic therapy
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Describe *Orchiectomy*
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- First line - Removal of testes - Testosterone drop to castrate levels - Relatively inexpensive
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What are some side effects of *Orchiectomy*?
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- Hot flashes - Impotence
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What are the four pharmacologic agents that can be used in place of *Orchiectomy*?
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- Anti-androgens - Combined hormonal blockade - Gonadotropin-releasing hormone antagonists - Lutenizing hormone-releasing hormone agonists
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What is the first line pharmacologic agent for hormonal therapy and why?
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LNRH agonists - Chemical castration - As effective as orchiectomy - Reversible
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What are the three LNRH agents?
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- Goserelin - Leuprolide - Triptorelin
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Describe *LNRH agonist flare up*
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- Due to initial brief surge of LH and FSH resulting in increased testosterone production - Manifests as bone pain or increased urinary symptoms - Resolves in about 2 weeks
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How can you prevent *LNRH agonist flare up*?
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Addition of anti-androgen x 7-14 days to combat initial testosterone surge
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When would *LNRH agonists* be contraindicated?
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With urethral obstruction or painful body metastases
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How long does it take to reach castrate levels with *LNRH agonists*?
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3-4 weeks
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What are the acute adverse effects of *LNRH agonists*?
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- Edema - Erectile dysfunction - Gynecomastia - Hot flashes - Injection site reaction - Tumor flare
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What are the long term adverse effects of *LNRH agonists*?
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- Clinical fracture - Obesity - Osteoporosis - Increased risk of diabetes and CV events - Insulin resistance
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What can be given for *combined androgen blockade*?
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- Anti androgen (Flutamide and Bicalutamide) + LNRH agonists - Orchiectomy + Nilutamide
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When would CAB be appropriate?
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- Androgen ablation is incomplete when on LNRH agonist - Beneficial in patients with minimal disease - Prevents tumor flare up
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What are some second line therapies available?
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- Aminoglutethimide - Corticosteroids - Ketoconazole - Megestrol acetate
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Describe *hormone refractory prostate cancer*
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Androgen independent cells continue to grow despite hormone manipulation
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What are some mechanisms that can cause *hormone refractory prostate cancer*?
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- Increased androgenic steroid production - Increased androgenic receptor levels - Receptor mutations - Tumor stimulation from extra-testicular androgens
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How can you treat *hormone refractory prostate cancer*?
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- Castration alone: add anti-androgen - If CAB was used: withdraw anti-androgen or change the anti-androgen
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Define *Metastatic Castration resistant prostate cancer*
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- Testosterone < 20 ng/dL and disease progression - Goal: Maintain serum testosterone at castrate levels
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What are the treatment options available for the treatment of *Metastatic Castration resistant prostate cancer*?
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- Docetaxel & prednisone (first line) - Enzalutamide - Abiraterone & prednisone - Mitoxantrone
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Describe *Abiraterone*
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- Used in combo with prednisone - MOA: androgen biosynthesis inhibitor via CYPC17 to decrease production of DHEA and androstenedione
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Describe the administration of *Abiraterone*
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1000 mg PO QD
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Who should chemotherapy be reserved for?
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Castration-recurrent metastatic disease
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What is the first line chemotherapy for *Castration-recurrent metastatic disease*?
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Docetaxel 75 mg/m2 + prednisone 5 mg PO BID for 10 cycles q21 days
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What are the adverse effects of *Docetaxel + prednisone*?
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- Alopecia - Fluid retention (administer steroids) - Hypersensitivity (pre medicate with steroids/antihistamine) - Myelosuppression - Peripheral neuropathy
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Describe *Cabazitaxel + prednisone*
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Second line for castration-resistant prostate cancer that has progressed or followed docetaxel therapy
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What are the side effects of *Cabazitaxel*?
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- Asthenia - Diarrhea - Fatigue - Infection - Neutropenic fever - Renal failure - Black box for hypersensitivity
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Describe immunotherapy with *Sipuleucel-T*
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- Vaccine designed to stimulate T-cell response to prostatic acid phosphatase - Use in asymptomatic or minimally symptomatic metastatic castrate-resistance prostate cancer - 3 sessions, 2 weeks apart
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True or false: *Sipuleucel-T* is the first vaccine approved for the treatment of cancer
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TRUE
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Describe *Enzalutamide*
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- Androgen receptor inhibitor approved after prior treatment with Docetaxel - Seizure warning!! - Drug interactions w/ CYP3A4 and CYP2C8 - Place in therapy: after chemo vs abiraterone
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What are some things you can give for *bone pain management* in metastatic prostate cancer?
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- Analgesics - Bisphosphonates - Radiation - Radiopharmaceuticals - Steroids
