BME 301Lecture FourteenProstate CancerEarly DetectionProstate gland contributes enzymes, nutrients and other secretions to semen.http://cwx.prenhall.com/bookbind/pubbooks/silverthorn2/medialib/Image_Bank/CH24/FG24_09a.jpgStatistics on Prostate Cancer United States: 218,890 new cases in US 27,050 deaths in US 2ndleading cause of cancer death in men Worldwide: Third most common cancer in men 679,000 new cases each yearGlobal Burden of Prostate Cancer Figure 5.45Risk factors Age chance of having prostate cancer rises rapidly after age 50 about 2 out of 3 prostate cancers are found in men over the age of 65. Race incidence 3x higher in African Americans occurs less often in Asian-American and Hispanic/Latino men than in non-Hispanic whites. Family History Having a father or brother with prostate cancer more than doubles a man's risk of developing prostate cancerRisk of Prostate Cancer in Next 5 Yrs0.0%0.5%1.0%1.5%2.0%2.5%3.0%3.5%4.0%4.5%<50 50-59 60-69 70-79 >80Current Age (Yrs)Development of Prostate Cancer Prostate Cancer: Slow, but continuously growing neoplasia Preclinical form develops at age 30 Remains latent for up to 20 years Can progress to aggressive, malignant cancer Peak incidence: 7thdecade of life Signs and symptoms: Often asymptomatic in early stages Weak or interrupted urine flow Inability to urinate These are symptoms of prostate enlargementNormal Prostatehttp://www.prostatitis.org/1normalgland.gifhttp://www.histol.chuvashia.com/images/male/prostate-01.jpgNormal GlandPre-cancerousGlandshttp://medlib.med.utah.edu/WebPath/jpeg1/MALE116.jpghttp://medlib.med.utah.edu/WebPath/jpeg1/MALE138.jpgProstate Cancerhttp://medgen.genetics.utah.edu/photographs/diseases/thumbnails/male074_small.Prostate Cancer (2005) Screening (American Cancer Society recs): Annual serum PSA test beginning at age 50 Annual digital rectal exam at age 50 Treatment: Surgery, radiation therapy, hormone therapy, chemotherapy 5 year survival All stages: 98% Localized disease: 100% Distant metastases: 31%PSA TestSolid surfacePSAEnzymeReporterSandwich ELISASensitivity = 63-83%Specificity = 90%Normal PSA Levels: < 4 ng/mlCancer Patients:20-25% have PSA < 4 ng/ml20-25% have 4 ng/ml < PSA < 10 ng/ml50-60% have PSA > 10 ng/mlDigital Rectal ExaminationWhat happens if DRE & PSA are +? Biopsy of prostate ($1500) Insert needle through wall of rectum into prostate Remove fragments of prostate Examine under microscopehttp://my.webmd.com/NR/rdonlyres/0557C509-969D-4441-A7BE-1236F9623C2F.jpegRx for Localized Prostate Cancer Radical prostatectomy (remove prostate) Usually curative Serious side effects: Incontinence (2-30%) Impotence (30-90%) Infertility Conservative management Just watch until symptoms developDoes Early Detection Make a Δ? 10 Yr Survival Rates for Localized Prostate CA: Grade I: Surgery 94% Conservative Rx 93% Grade II: Surgery 87% Conservative Rx 77% Grade III: Surgery 67% Conservative Rx 45% Makes a difference only for high grade diseaseChallenges of Screening Prostate cancer is a slow-growing cancer Not symptomatic for an average of 10 years Most men with prostate cancer die of other causes Treatment has significant side effects 50 year old man: 40% chance of developing microscopic prostate cancer 10% chance of having this cancer diagnosed 3% chance of dying of itShould we screen? Yes: Localized prostate cancer is curable Advanced prostate cancer is fatal Some studies (not RCTs) show decreased mortality in screened patients No: False-positives lead to unnecessary biopsies Over-detection of latent cancers We will detect many cancers that may never have produced symptoms before patients died of other causes (slow growing cancer of old age) No RCTs showing decreased mortalityWhy are RCTs so Important?Lead Time BiasClinical Evidence Three case-control studies of DRE Mixed results One completed RCT of DRE & PSA Found no difference in # of prostate cancer deaths between groups randomized to screening and usual careRandomized Clinical Trials Underway Prostate Cancer vs. Intervention Trial (US) Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (US) European Randomized Study for Screening for Prostate Cancer 239,000 men 10 countries Will be complete in 2008Do All Countries Screen with PSA? United States: Conflicting recommendations Europe: No Not enough evidence that screening reduces mortalityConflicting Recommendations in US Guide to Clinical Preventive Services Do NOT screen using DRE or serum PSA American College of Preventive Medicine Men aged 50 or older with >10 yr life expectance should be informed and make their own decision American Cancer Society (and others) Men aged 50 or older with > 10 yr life expectancy should be screened with DRE and serum PSAUSPSTF Recommendation The USPSTF found: good evidence that PSA screening can detect early-stage prostate cancer but mixed and inconclusive evidence that early detection improves health outcomes. Screening is associated with important harms, including frequent false-positive results and unnecessary anxiety, biopsies and potential complications of treatment of some cancers that may never have affected a patient’s health. The USPSTF concludes: that evidence is insufficient to determine whether the benefits outweigh the harms for a screened population.American Cancer Society (2008): PSA and DRE should be offeredannually, beginning at age 50, to men who have at least a 10-year life expectancy. Information should be provided about what is known and what is uncertain about benefits, limitations, and harms of early detection and treatment of prostate cancer so they can make an informed decision. Men who ask their doctor to make the decision on their behalf should be tested. Discouraging testing is not appropriate. Also, not offering testing is not appropriate.PSA TestDetailsThe PSA Test What is PSA? Prostate-specific antigen A glycoprotein responsible for liquefaction of semen Highly specific for prostate (only made by the prostate) PSA test is a blood test to measure PSA levels Why measure PSA to screen for cancer? PSA levels are closely (but not definitively) associated with prostate cancer May be
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