6 – Prostate Cancer – Flashcards
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--What are the age related risk factors for prostate cancer?
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More than 70% of cases dx are >65 y/o (rare to see men under age 40)
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--What are the race related risk factors for prostate cancer?
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Highest incidence among African Americans (49% of all cases)
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--What are the genetic related risk factors for prostate cancer?
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15% lifetime risk if pt has a first degree relative w/ hx of prostate cancer; 9% risk d/2 other heritable susceptibility genes; Familial prostate cancer inherited in an autosomal dominant manner; Mutations (p53, Rb, BRCA, E-cahedrin, etc)
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--What are the occupational related risk factors for prostate cancer?
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Textile workers and those exposed to industrial chemicals may be at higher risk (said about any cancer, to be honest)
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--What are the diet related risk factors for prostate cancer?
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High fat diet may increase risk of dz. However, diet rich in selenium, soy, lycopene, and vitamin E may protect.
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--In addition to accurate hx, complete physical exam, and assessment of risk factors, what screening is warranted for prostate cancer?
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Prostate-Specific Antigen (PSA) levels +/- Digital Rectal Exam (DRE)
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--Describe the Prostate-Specific Antigen (PSA).
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PSA is a glycoprotein produced by epithelial cells of the prostate --Specific to the prostate, not specific for cancer --Factors that increase PSA: ejaculation, prostatic manipulation, DRE --Factors that decrease PSA: finasteride, dutasteride --Unpredictable effects on PSA: saw palmetto, androgen receptor blockers
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--Describe the Digital Rectal Exam (DRE).
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Normal prostate has consistency the same as the tip of the nose; Prostate cancer more like consistency of chin; --Lumps, hardness, inability to move the prostate --> further eval --25-50% of masses are cancer --Sensitivity 69-89%, specificity 84-98%, positive predictive value 26-35% Debatable use
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--What kind of prostate cancer screening is recommended for men aged 50-70 (most beneficial age range)?
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DRE and PSA --If DRE normal and PSA <3ng/mL repeat at 1-2 year intervals
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--What kind of prostate cancer screening is recommended for men aged 40-49 (high-risk, which is subjective to your assessment of risk factors)?
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DRE and PSA --If PSA 1 and DRE normal, repeat at 1-2 year intervals
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--What kind of prostate cancer screening is recommended for men aged >70 (healthy with no comorbidities)?
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DRE and PSA --May have a higher PSA cut off (>4ng/mL?) --Benefit is debatable and based on patient activity/quality of life
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--What is a TRUS?
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Transrectal Ultrasonography
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--When is TRUS indicated?
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With abnormal DRE regardless of PSA level and/or abnormal PSA >3ng/mL
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--Which agents and doses may be used for prostate cancer chemoprevention (though neither agent is FDA approved)?
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5α-reductase inhibitors (inhib testosterone into DHT): *finasteride* 5 mg QD or *dutasteride* 0.5 mg QD
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--Chemoprevention of prostate cancer may be beneficial in which patients (based on discussion, pt risk factors, etc)?
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Asymptomatic, w/ PSA <3, who are screened regularly
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--What are our initial tests for prostate cancer?
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DRE, PSA, TRUS if either DRE or PSA is positive, biopsy
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--What are our staging tests for prostate cancer?
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Gleason score on biopsy specimen (to determine differentiation) Bone scan (to see metastases) Complete blood count Liver function tests Serum phosphatases (acid/alkaline) Excretory urogram (to detect spread) Chest x-ray (to detect spread) Lymph node evaluation (to detect spread)
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--What is "Gleason Scoring"?
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Used to determine how advanced the disease is based upon how differentiated the cells are (Grade 5 is worst)
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--What is the AUS classification of prostate cancer?
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A-D: A: occult, non-palpable B: confined to prostate C: localized to periprostatic area D: metastatic disease
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--What components are usually used together to stage prostate cancer?
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TNM staging, Gleason score, description
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--As part of TNM staging, what are T1-4 stages of prostate cancer?
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T1: tumor neither palpable nor visible by imaging T2: tumor confined to prostate T3: tumor extends through prostatic capsule T4: tumor invades adjacent structure other then seminal vesicles
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--How may prostate cancers clinically present?
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Usually no discernible sx in early stage dz; Urinary freq, urgency, nocturia, hesitation - common but usually related to concomitant benign prostate dz; Bone pain, pelvic discomfort, ED, and blood in the semen may be signs of more adv dz
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--What is the most frequent cancer among men in the US?
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Prostate cancer
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--What are the three enzymes we tend to look at when treating prostate cancer, which are involved in the synthesis of testosterone from cholesterol?
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CYP17: 17α-hydroxylase 5α-reductase CYP19: aromatase (minor enzyme responsible, not looked at too much for tx)
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--Which enzyme changes 17α-hydroxypregnenolone into 17α-hydroxyprogesterone?
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CYP17: 17α-hydroxylase
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--Which enzyme changes testosterone into estradiol?
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CYP19: aromatase
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--Which enzyme changes testosterone into dihydrotestosterone (DHT)?
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5α-reductase
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--In general, what are the 3 main risk factors for prostate cancer?
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Age, race, & genetics
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--Why may PSA be preferred to DRE for screening of prostate cancer?
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PSA test is indicating cancers which are mostly localized and DRE is finding cancers which have begun to progress already. However, PSA can miss diagnoses b/c there are several things that can alter the test.
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--What two staging systems are used to classify prostate cancer extent?
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TNM staging or AUS classification (A-D)
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--How does cancer spread?
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Lymph nodes, blood, tissue (spread into local area)
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--What stage(s) of prostate cancer have metastases or lymph node involvement?
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Stage IV
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--What are the goals of tx for early stage or localized prostate cancer?
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Minimize morbidity & mortality Watchful waiting & active surveillance Radical Prostatectomy Radiation Androgen deprivation therapy (ADT)
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--What are the goals of tx for advanced prostate cancer?
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Stage D: not curable Focus on sx relief and maintaining quality of life Androgen deprivation therapy (ADT) Chemotherapy
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--What are our nonpharm tx options for prostate cancer?
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Expectant management/Watchful waiting & active surveillance Orchiectomy (removal of testes) Radiation Radical Prostatectomy Diet mgmt
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--What is "active surveillance" wrt prostate cancer?
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PSA no more than q6mo DRE no more than q12mo Fine needle biopsy q12mo (to prompt curative tx if conversion of biopsy)
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--What is "observation" wrt prostate cancer?
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PSA no more than q6mo DRE no more than q12mo Continues until symptoms are present or are eminent (PSA>100) and require palliative ADT, goal is not to tx.
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--Wrt prostate cancer, consider active surveillance for:
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Very low risk prostate cancer & estimated life expectancy > 20 years or 10-20 years Low risk prostate cancer & estimated life expectancy of > 10 years
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--Wrt prostate cancer, consider observation for:
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Low risk prostate cancer & estimated life expectancy < 10 years
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--Wrt prostate cancer, what are some decisive factors for active surveillance?
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Individualized Life expectancy Disease characteristics Performance status Potential side effects of treatment Patient decision
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--What are some complications of radical prostatectomy?
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Blood loss, incontinence, impotence, anesthesia risk
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--When do we see benefit with radical prostatectomy and when do we use this option?
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Beneficial if tumor confined to prostate Reserved for those with estimated life expectancy > 10 years Also, nerve sparing - 50-80% regain sexual potency in 1 year
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--What are our radiation therapy options for prostate cancer?
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External beam --completed over several visits Brachytherapy (beans implanted) --1 day tx Overall, an option for pts who are not surgical candidates
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--For prostate cancer, which tends to be preferred (although they appear equivalent in outcomes): surgery or radiation?
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Surgery
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--What are some complications of radiation therapy for prostate cancer?
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Impotence (30%) Rectal/bladder abnormalities
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--Wrt prostate cancer, what is ADT?
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Androgen deprivation therapy --Bilateral surgical orchiectomy, medical castration, block androgen receptors --Reduces the number of circulating androgens --Blocks the androgen receptors
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--What are the components of ADT?
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LHRH agonist + antiandrogen or orchiectomy --However, "the optimal level of serum testosterone to effect castration has yet to be determined"
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--What is the purpose of LHRH agonist in ADT?
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To create ↑ testosterone to promote negative feedback; We see disease flare - caused by initial induction of LH & FSH by the agonist leading to initial increase in testosterone production-->Usually resolves in 2 weeks
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--Orchiectomy is a preferred option in prostate cancer tx for:
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Impending spinal cord compression Ureteral obstruction
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--What are our LHRH agonist agents, which are as effective as orchiectomy?
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Goserelin (Zoladex ®) Leuprolide (Lupron ®, Eligard ®) Triptorelin (Trelstar ®) (choice based on cost / dosing schedule)
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--Which LHRH agonist may be given every 6 months?
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leuprolide or triptorelin
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--What are the ADRs of our LHRH agonists (goserelin, leuprolide, triptorelin) in prostate CA?
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Acute: disease flare during 1st week, hot flashes, erectile dysfunction, injection site reaction Long-term: osteoporosis, skeletal fractures, insulin resistance, increased risk of diabetes and cardiovascular disease
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--What is our gonadotropin releasing hormone (GnRH) antagonist agent? MoA?
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degarelix Reversibly binds to GnRH receptors in the pituitary gland, decreasing production of testosterone to castrate levels, see immediate effect
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--What are the ADRs of degarelix?
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Injection site reactions, elevation in LFTs
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--What are the advantages of degarelix?
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Immediate down regulation of testosterone, eliminates tumor flare/antiandrogen use
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--What are our antiandrogen agents (which block the action of androgens, not production, and are used most often in tx of prostate cancer)?
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flutamide bicalutamide nilutamide abiraterone enzalutamide
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--What are the ADRs of flutamide, bicalutamide, and nilutamide?
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*Gynecomastia*, hot flushes, diarrhea, LFT abnormalities, breast tenderness, methemoglobinemia, hematuria --visual disturbances and EtOH intolerance with nilutamide
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--By what route are we giving all of our antiandrogen agents?
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Oral
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--Wrt prostate cancer, what is CAB?
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Combined androgen blockade --Medical or surgical castration (LHRH agonist or orchiectomy) & antiandrogen
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--What is the goal of metastatic prostate cancer tx?
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Palliation & prolong survival
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--What are our options for metastatic prostate cancer tx?
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First line = ADT Orchiectomy LHRH agonist + antiandrogen x 7 days LHRH agonist + antiandrogen GnRH antagonist
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--What are our second line options for metastatic prostate cancer?
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Antiandrogen withdrawal (20-30% response) Corticosteroids Ketoconazole (inhib androgen synthesis, ADR of gynecomastia, supplement with CSs)
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--What are our 1st line options for metastatic castrate resistant prostate cancer (CRPC)?
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Docetaxel + prednisone (Standard of care) Docetaxel + estramustine + prednisone Mitoxantrone + prednisone (no survival benefit) Abiraterone (used with prednisone) Enzalutamide
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--What is the dosing of docetaxel + prednisone for metastatic castrate resistant prostate cancer?
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Docetaxel 75mg/m2 every 3 weeks + prednisone 5mg BID (caution with elevated Tbili or liver enzymes >2.5x)
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--What are the side effects of docetaxel + prednisone for prostate cancer tx?
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Alopecia, nausea, bone marrow suppression, fluid retention --Corticosteroid given prior to start in order to reduce fluid retention
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--What is the dosing of Docetaxel + Estramustine + Prednisone?
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Docetaxel 60mg/m2 + estramustine 280mg TID - days 1-5 + prednisone 5mg BID
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--What are the caveats with docetaxel + estramustine + prednisone tx for prostate cancer?
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Estramustine needs to be refrigerated, calcium inhibits absorption
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--How does estramustine work to tx prostate cancer?
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Causes a decrease in testosterone and an increase in estrogen
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--What is the MoA of abiraterone in prostate cancer?
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Selective, irreversible CYP 17 inhibitor --> androgen synthesis inhibition
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--What is the place in prostate cancer chemotherapy of abiraterone or enzalutamide?
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First-line; Also, may extend survival in patients who progressed on docetaxel
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--What is the MoA of enzalutamide (Xtandi) for prostate cancer?
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Androgen receptor inhibitor
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--What are some of the ADRs with abiraterone (Zytiga)?
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Fatigue, edema, hypertension, increased serum triglycerides, hepatotoxicity
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--What are some of the ADRs with enzalutamide (Xtandi)?
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Fatigue, diarrhea, hot flashes, headache, seizures
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--What is the dosing of enzalutamide?
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140mg PO QD
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--What is the dosing of abiraterone and important timing considerations?
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1000mg po daily on an empty stomach, at least 1 hour before and 2 hours after food + prednisone 5mg BID (which should be taken with food)
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--What are our second line options for advanced castrate resistant prostate cancer where the pt has prior enzalutamide/abiraterone use and no visceral metastases?
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Docetaxel with prednisone Abiraterone acetate Enzalutamide Radium-223 (if bone disease)
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--What are our second line options for advanced castrate resistant prostate cancer where the pt has prior enzalutamide/abiraterone use and visceral metastases?
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Docetaxel with prednisone
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--What are our second line options for advanced castrate resistant prostate cancer where the pt has prior docetaxel use and no visceral metastases?
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Enzalutamide Abiraterone acetate with prednisone Cabazitaxel with prednsone
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--What are our second line options for advanced castrate resistant prostate cancer where the pt has prior docetaxel use and visceral metastases?
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Enzalutamide Abiraterone with prednisone Cabazitaxel with prednisone
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--What is the inidication for sipuleucel-T (Provenge) immunotherapy in prostate cancer?
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Asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (CRPC), good PFS, life expectancy > 6 months
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--In castrate resistant prostate cancer pts with bone metastases, what agents have been studied to prevent complications?
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denosumab and zolendronic acid *However, carry risk of bone fractures, hypocalcemia, and osteonecrosis of the jaw. Important to supplement with adequate calcium and vit D*
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