question

--Which hormone is a growth signal for prostate tissue?

answer

Testosterone

question

--How are genetics linked to prostate cancer?

answer

There is a rare, autosomal dominant gene which accounts for 9% of all prostate cancer and 45% of cases in men <55 y/o

question

--What is a prostatic intraepithelial neoplasia (PIN)?

answer

A premalignant lesion that may precede prostate cancer by up to 10 years

question

--What is the most freq cancer among men in US? Median age?

answer

Prostate cancer; 66 y/o

question

--What are the age related risk factors for prostate cancer?

answer

More than 70% of cases dx are >65 y/o (rare to see men under age 40)

question

--What are the race related risk factors for prostate cancer?

answer

Highest incidence among African Americans (49% of all cases)

question

--What are the genetic related risk factors for prostate cancer?

answer

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)

question

--What are the occupational related risk factors for prostate cancer?

answer

Textile workers and those exposed to industrial chemicals may be at higher risk (said about any cancer, to be honest)

question

--What are the diet related risk factors for prostate cancer?

answer

High fat diet may increase risk of dz. However, diet rich in selenium, soy, lycopene, and vitamin E may protect.

question

--In addition to accurate hx, complete physical exam, and assessment of risk factors, what screening is warranted for prostate cancer?

answer

Prostate-Specific Antigen (PSA) levels +/- Digital Rectal Exam (DRE)

question

--Describe the Prostate-Specific Antigen (PSA).

answer

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

question

--Describe the Digital Rectal Exam (DRE).

answer

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

question

--What kind of prostate cancer screening is recommended for men aged 50-70 (most beneficial age range)?

answer

DRE and PSA --If DRE normal and PSA <3ng/mL repeat at 1-2 year intervals

question

--What kind of prostate cancer screening is recommended for men aged 40-49 (high-risk, which is subjective to your assessment of risk factors)?

answer

DRE and PSA --If PSA 1 and DRE normal, repeat at 1-2 year intervals

question

--What kind of prostate cancer screening is recommended for men aged >70 (healthy with no comorbidities)?

answer

DRE and PSA --May have a higher PSA cut off (>4ng/mL?) --Benefit is debatable and based on patient activity/quality of life

question

--What is a TRUS?

answer

Transrectal Ultrasonography

question

--When is TRUS indicated?

answer

With abnormal DRE regardless of PSA level and/or abnormal PSA >3ng/mL

question

--Which agents and doses may be used for prostate cancer chemoprevention (though neither agent is FDA approved)?

answer

5α-reductase inhibitors (inhib testosterone into DHT): *finasteride* 5 mg QD or *dutasteride* 0.5 mg QD

question

--Chemoprevention of prostate cancer may be beneficial in which patients (based on discussion, pt risk factors, etc)?

answer

Asymptomatic, w/ PSA <3, who are screened regularly

question

--What are our initial tests for prostate cancer?

answer

DRE, PSA, TRUS if either DRE or PSA is positive, biopsy

question

--What are our staging tests for prostate cancer?

answer

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)

question

--What is "Gleason Scoring"?

answer

Used to determine how advanced the disease is based upon how differentiated the cells are (Grade 5 is worst)

question

--What is the AUS classification of prostate cancer?

answer

A-D: A: occult, non-palpable B: confined to prostate C: localized to periprostatic area D: metastatic disease

question

--What components are usually used together to stage prostate cancer?

answer

TNM staging, Gleason score, description

question

--As part of TNM staging, what are T1-4 stages of prostate cancer?

answer

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

question

--How may prostate cancers clinically present?

answer

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

question

--What is the most frequent cancer among men in the US?

answer

Prostate cancer

question

--What are the three enzymes we tend to look at when treating prostate cancer, which are involved in the synthesis of testosterone from cholesterol?

answer

CYP17: 17α-hydroxylase 5α-reductase CYP19: aromatase (minor enzyme responsible, not looked at too much for tx)

question

--Which enzyme changes 17α-hydroxypregnenolone into 17α-hydroxyprogesterone?

answer

CYP17: 17α-hydroxylase

question

--Which enzyme changes testosterone into estradiol?

answer

CYP19: aromatase

question

--Which enzyme changes testosterone into dihydrotestosterone (DHT)?

answer

5α-reductase

question

--In general, what are the 3 main risk factors for prostate cancer?

answer

Age, race, & genetics

question

--Why may PSA be preferred to DRE for screening of prostate cancer?

answer

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.

question

--What two staging systems are used to classify prostate cancer extent?

answer

TNM staging or AUS classification (A-D)

question

--How does cancer spread?

answer

Lymph nodes, blood, tissue (spread into local area)

question

--What stage(s) of prostate cancer have metastases or lymph node involvement?

answer

Stage IV

question

--What are the goals of tx for early stage or localized prostate cancer?

answer

Minimize morbidity & mortality Watchful waiting & active surveillance Radical Prostatectomy Radiation Androgen deprivation therapy (ADT)

question

--What are the goals of tx for advanced prostate cancer?

answer

Stage D: not curable Focus on sx relief and maintaining quality of life Androgen deprivation therapy (ADT) Chemotherapy

question

--What are our nonpharm tx options for prostate cancer?

answer

Expectant management/Watchful waiting & active surveillance Orchiectomy (removal of testes) Radiation Radical Prostatectomy Diet mgmt

question

--What is "active surveillance" wrt prostate cancer?

answer

PSA no more than q6mo DRE no more than q12mo Fine needle biopsy q12mo (to prompt curative tx if conversion of biopsy)

question

--What is "observation" wrt prostate cancer?

answer

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.

question

--Wrt prostate cancer, consider active surveillance for:

answer

Very low risk prostate cancer & estimated life expectancy > 20 years or 10-20 years Low risk prostate cancer & estimated life expectancy of > 10 years

question

--Wrt prostate cancer, consider observation for:

answer

Low risk prostate cancer & estimated life expectancy < 10 years

question

--Wrt prostate cancer, what are some decisive factors for active surveillance?

answer

Individualized Life expectancy Disease characteristics Performance status Potential side effects of treatment Patient decision

question

--What are some complications of radical prostatectomy?

answer

Blood loss, incontinence, impotence, anesthesia risk

question

--When do we see benefit with radical prostatectomy and when do we use this option?

answer

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

question

--What are our radiation therapy options for prostate cancer?

answer

External beam --completed over several visits Brachytherapy (beans implanted) --1 day tx Overall, an option for pts who are not surgical candidates

question

--For prostate cancer, which tends to be preferred (although they appear equivalent in outcomes): surgery or radiation?

answer

Surgery

question

--What are some complications of radiation therapy for prostate cancer?

answer

Impotence (30%) Rectal/bladder abnormalities

question

--Wrt prostate cancer, what is ADT?

answer

Androgen deprivation therapy --Bilateral surgical orchiectomy, medical castration, block androgen receptors --Reduces the number of circulating androgens --Blocks the androgen receptors

question

--What are the components of ADT?

answer

LHRH agonist + antiandrogen or orchiectomy --However, "the optimal level of serum testosterone to effect castration has yet to be determined"

question

--What is the purpose of LHRH agonist in ADT?

answer

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

question

--Orchiectomy is a preferred option in prostate cancer tx for:

answer

Impending spinal cord compression Ureteral obstruction

question

--What are our LHRH agonist agents, which are as effective as orchiectomy?

answer

Goserelin (Zoladex ®) Leuprolide (Lupron ®, Eligard ®) Triptorelin (Trelstar ®) (choice based on cost / dosing schedule)

question

--Which LHRH agonist may be given every 6 months?

answer

leuprolide or triptorelin

question

--What are the ADRs of our LHRH agonists (goserelin, leuprolide, triptorelin) in prostate CA?

answer

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

question

--What is our gonadotropin releasing hormone (GnRH) antagonist agent? MoA?

answer

degarelix Reversibly binds to GnRH receptors in the pituitary gland, decreasing production of testosterone to castrate levels, see immediate effect

question

--What are the ADRs of degarelix?

answer

Injection site reactions, elevation in LFTs

question

--What are the advantages of degarelix?

answer

Immediate down regulation of testosterone, eliminates tumor flare/antiandrogen use

question

--What are our antiandrogen agents (which block the action of androgens, not production, and are used most often in tx of prostate cancer)?

answer

flutamide bicalutamide nilutamide abiraterone enzalutamide

question

--What are the ADRs of flutamide, bicalutamide, and nilutamide?

answer

*Gynecomastia*, hot flushes, diarrhea, LFT abnormalities, breast tenderness, methemoglobinemia, hematuria --visual disturbances and EtOH intolerance with nilutamide

question

--By what route are we giving all of our antiandrogen agents?

answer

Oral

question

--Wrt prostate cancer, what is CAB?

answer

Combined androgen blockade --Medical or surgical castration (LHRH agonist or orchiectomy) & antiandrogen

question

--What is the goal of metastatic prostate cancer tx?

answer

Palliation & prolong survival

question

--What are our options for metastatic prostate cancer tx?

answer

First line = ADT Orchiectomy LHRH agonist + antiandrogen x 7 days LHRH agonist + antiandrogen GnRH antagonist

question

--What are our second line options for metastatic prostate cancer?

answer

Antiandrogen withdrawal (20-30% response) Corticosteroids Ketoconazole (inhib androgen synthesis, ADR of gynecomastia, supplement with CSs)

question

--What are our 1st line options for metastatic castrate resistant prostate cancer (CRPC)?

answer

Docetaxel + prednisone (Standard of care) Docetaxel + estramustine + prednisone Mitoxantrone + prednisone (no survival benefit) Abiraterone (used with prednisone) Enzalutamide

question

--What is the dosing of docetaxel + prednisone for metastatic castrate resistant prostate cancer?

answer

Docetaxel 75mg/m2 every 3 weeks + prednisone 5mg BID (caution with elevated Tbili or liver enzymes >2.5x)

question

--What are the side effects of docetaxel + prednisone for prostate cancer tx?

answer

Alopecia, nausea, bone marrow suppression, fluid retention --Corticosteroid given prior to start in order to reduce fluid retention

question

--What is the dosing of Docetaxel + Estramustine + Prednisone?

answer

Docetaxel 60mg/m2 + estramustine 280mg TID - days 1-5 + prednisone 5mg BID

question

--What are the caveats with docetaxel + estramustine + prednisone tx for prostate cancer?

answer

Estramustine needs to be refrigerated, calcium inhibits absorption

question

--How does estramustine work to tx prostate cancer?

answer

Causes a decrease in testosterone and an increase in estrogen

question

--What is the MoA of abiraterone in prostate cancer?

answer

Selective, irreversible CYP 17 inhibitor --> androgen synthesis inhibition

question

--What is the place in prostate cancer chemotherapy of abiraterone or enzalutamide?

answer

First-line; Also, may extend survival in patients who progressed on docetaxel

question

--What is the MoA of enzalutamide (Xtandi) for prostate cancer?

answer

Androgen receptor inhibitor

question

--What are some of the ADRs with abiraterone (Zytiga)?

answer

Fatigue, edema, hypertension, increased serum triglycerides, hepatotoxicity

question

--What are some of the ADRs with enzalutamide (Xtandi)?

answer

Fatigue, diarrhea, hot flashes, headache, seizures

question

--What is the dosing of enzalutamide?

answer

140mg PO QD

question

--What is the dosing of abiraterone and important timing considerations?

answer

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)

question

--What are our second line options for advanced castrate resistant prostate cancer where the pt has prior enzalutamide/abiraterone use and no visceral metastases?

answer

Docetaxel with prednisone Abiraterone acetate Enzalutamide Radium-223 (if bone disease)

question

--What are our second line options for advanced castrate resistant prostate cancer where the pt has prior enzalutamide/abiraterone use and visceral metastases?

answer

Docetaxel with prednisone

question

--What are our second line options for advanced castrate resistant prostate cancer where the pt has prior docetaxel use and no visceral metastases?

answer

Enzalutamide Abiraterone acetate with prednisone Cabazitaxel with prednsone

question

--What are our second line options for advanced castrate resistant prostate cancer where the pt has prior docetaxel use and visceral metastases?

answer

Enzalutamide Abiraterone with prednisone Cabazitaxel with prednisone

question

--What is the inidication for sipuleucel-T (Provenge) immunotherapy in prostate cancer?

answer

Asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (CRPC), good PFS, life expectancy > 6 months

question

--In castrate resistant prostate cancer pts with bone metastases, what agents have been studied to prevent complications?

answer

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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