Prostate Cancer: Evaluation & New Treatments Christopher L. Coogan, M.D. Charles F. McKiel, M.D. Kalyan C. Latchamsetty, M.D. В©2007 RUSH University Medical Center What is the prostate? • Male sexual gland • Adds nutrients and fluids for sperm • This fluid is added to sperm during ejaculation • Urethra (urine channel) runs through the middle of the prostate • Weight ~ 20 – 30gms В©2007 RUSH University Medical Center Anatomy • 1 = Peripheral Zone – 75% of CA • 2 = Central Zone – 5% of CA • 3 = Transitional Zone – 20% of CA • 4 = Anterior Fibromuscular Zone – CA rare В©2007 RUSH University Medical Center What is prostate cancer? • Abnormal cells growing without regulation • Spreads and invades local tissues • Prostate Cancer… – Begins with a small tumor in the gland – First spreads to the local lymph nodes – Then spreads to the bony skeleton and other areas of the body В©2007 RUSH University Medical Center Introduction • CAP пѓ most commonly diagnosed (non-skin) cancer in American в™‚ • 2nd most common cause of в™‚ cancer death • ~ 217,730 new cases of CAP in 2010 • American Cancer Society • ~ 32,050 deaths in 2010 in the U.S. В©2007 RUSH University Medical Center Incidence of prostate cancer В©2007 RUSH University Medical Center What are the symptoms of prostate cancer? • You might not have any at all! – Often there are none, or they are not recognized • Major symptoms: – – – – – – Urinary frequency Slow urinary flow Painful urination Blood in urine or semen Impotence Lower back or thigh pain В©2007 RUSH University Medical Center How Significant Is Prostate Cancer? • In the USA, 217,730 men will be diagnosed with prostate cancer in 2010. That is one man diagnosed every 3 minutes • Prostate cancer deaths are estimated at 32,050 in 2010. That is one death every 18 minutes • In Illinois, 8,730 men were diagnosed in 2010 • 1,420 men died of prostate cancer during 2010 in Illinois Source: Cancer Facts and Figures –2006- American Cancer Society В©2007 RUSH University Medical Center Prostate cancer risk factors: пЃ¬ Age: The risk increases with age, but 25% of diagnoses are made under age 65. пЃ¬ Race: African-Americans have a rate of incidence double that of Caucasian men пЃ¬ Family history of prostate cancer: Men with a family history have two- to three-fold increase in the risk of prostate cancer пЃ¬ Diet: A diet high in saturated animal fat can double the risk of developing prostate cancer. В©2007 RUSH University Medical Center Risk Factors - Age AGE 0 - 39: 40 – 59 : 60 – 69 : 70 – 79 : 0 - Death : RISK 1 per 10149 1 per 38 1 per 14 1 per 7 1 per 6 Source: ACS 2000 to 2002 В©2007 RUSH University Medical Center Risk Factors - Race Race Afr.-Am. Cauc. Hisp. Asian Incidence 272.0 169.0 141.9 101.4 Death 68.1 27.7 23.0 12.1 Source: Rates per 100,000 and age-adjusted. SEER incidence and U.S. cancer death rates, 1975-2002, in (SEER = NCI Surveillance, Epidemiology, and End-Results Program В©2007 RUSH University Medical Center RACE • Prostate cancer is almost twice as common in AfricanAmerican men than in Caucasian men • African Americans are more than twice as likely to die when diagnosed than Caucasian men • Why? Uncertain. – – – – Socioeconomic Diet Genetic ??? В©2007 RUSH University Medical Center Risk Factors – Family History FAMILY HISTORY 2.4 times increased risk for men with a firstdegree relative All blood relatives need to be screened starting at the age of 40 (Spitz, et al, “Familial patterns of prostate cancer: A case-control analysis”, J Urol, 1991, 146:1305-1307) В©2007 RUSH University Medical Center Risk Factors - Diet Eating red meat increases the risk of developing prostate cancer 2.64 times пЃ® Red meat and dairy products are high in saturated fat rich in arachidonic acid (a fatty acid) пЃ® Vegetable oil is rich in alpha linolenic acid (a fatty acid) пЃ® By-products of these fats promote the growth and seriousness of prostate cancer пЃ® пЃ® Eating a diet high in fats also lowers the body’s defenses В©2007 RUSH University Medical Center Trends in Obesity* Prevalence (%), By Gender, Adults Aged 20 to 74, US, 1960-2002 45 40 33 Prevalence 35 30 28 30 26 23 25 21 20 15 17 16 17 15 13 15 11 12 13 10 5 0 Both sexes NHES I (1960-62) NHANES III (1988-94) Men Women NHANES I (1971-74) NHANES 1999-2002 NHANES II (1976-80) *Obesity is defined as a body mass index of 30 kg/m2 or greater. Source: National Health Examination Survey 1960-1962, National Health and Nutrition Examination Survey, 19711974, 1976-1980, 1988-1994, 1999-2002, National Center for Health Statistics, Centers for Disease Control and Prevention, 2002, 2004. В©2007 RUSH University Medical Center Trends in Overweight* Prevalence (%), Adults 18 and Older, US, 1992-2003 1992 Less than 50% 50 to 55% More than 55% State did not participate in survey *Body mass index of 25.0 kg/m2or greater Source: Behavioral Risk Factor Surveillance System, CD-ROM (1984-1995, 1998) and Public Use Data Tape (2003), National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 1997, 2000, 2004. В©2007 RUSH University Medical Center Trends in Overweight* Prevalence (%), Adults 18 and Older, US, 1992-2003 1995 Less than 50% 50 to 55% More than 55% State did not participate in survey *Body mass index of 25.0 kg/m2or greater Source: Behavioral Risk Factor Surveillance System, CD-ROM (1984-1995, 1998) and Public Use Data Tape (2003), National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, 1997, 2000, 2004. В©2007 RUSH University Medical Center Trends in Overweight* Prevalence (%), Adults 18 and Older, US, 1992-2003 1998 Less than 50% 50 to 55% More than 55% State did not participate in survey В©2007 RUSH University Medical Center Trends in Overweight* Prevalence (%), Adults 18 and Older, US, 1992-2003 2003 Less than 50% 50 to 55% More than 55% State did not participate in survey В©2007 RUSH University Medical Center So what CAN I eat? • A balanced diet rich in fruits and vegetables! (5 servings/day) • Lower your intake of red meat, processed and fried foods. Eat more plant-based food like soy protein. • Watch portion sizes (3 oz meat/serving) • Eat foods with lycopene (tomatoes, watermelon and red grapefruit) which may be associated with a decreased risk of prostate cancer В©2007 RUSH University Medical Center Can we prevent prostate cancer? • Prostate Cancer Prevention Trial (PCPT): 18,882 men randomized: – 25% Reduction in Cancer, BUT – 14-25% increase in high grade cancer • REDUCE Trial: 22% decreased – 8200 men, randomized, ? increase high grade – Dutasteride (Avodart) – FDA WARNING • SELECT Trial: 35,533 men – Vitamin E vs Selenium: no change В©2007 RUSH University Medical Center Screening • American Urological Association screening recommendations: • Digital Rectal Examination & PSA 1.All males over the age of 40 – annually – ?45 or 50 2.All African American males over age of 40 – annually 3.All pts with family hx (1st degree relative) starting at age 40 – annually • ACS: 50 – 45 if 1st degree or AA В©2007 RUSH University Medical Center Anatomy - DRE В©2007 RUSH University Medical Center DRE not always accurate! В©2007 RUSH University Medical Center Screening • Only 15% of prostate cancers are detected through this examination • Many men with abnormal DREs do NOT have prostate cancer • Many men with normal DREs DO have prostate cancer В©2007 RUSH University Medical Center PSA • Prostate specific antigen • Protein produced by the cells of the prostate • responsible for liquefying semen immediately following ejaculation – Increases motility of sperm cells – Aids in fertilization • Initially discovered in the late вЂ�70s, but wasn’t used for screening for CAP • Was used mainly by forensics in rape cases • In 1985, the FDA approved PSA test for use in humans В©2007 RUSH University Medical Center PSA • Can be elevated with benign conditions i.e. prostatitis, BPH, UTIs, urinary retention • Normal range: 0 - 4 ng/ml (0 - 2.5) • PSA rises as we age – PSA level of 3.0 in a 30 y/o male is abnormal – PSA level of 3.0 in a 70 y/o male is nl • PSA Velocity (>0.75/year) В©2007 RUSH University Medical Center PSA Screening • Most significant and controversial development in prostate cancer control over the last 20 years • Initial studies: – PSA markedly elevated in men with prostate cancer (but, also elevated with benign conditions: UTI, BPH, prostatitis, urinary retention) – PSA screening resulted in dramatic shift in stage of disease • Conclusive evidence of efficacy is still lacking! But, it’s the best test we have. • In late 1980s, PSA screening in US exploded В©2007 RUSH University Medical Center В©2007 RUSH University Medical Center SCIENCE TIMES, April 9 2002 В©2007 RUSH University Medical Center Prostate Cancer Screening • Tyrol Study: 54% reduction in mortality – 1993-2005 • PLCO Trial: No benefit to screening – If PSA <2.0, every 2 years • European Randomized Study for Screening for Prostate Cancer (ERSPC) – 20% reduction mortality, 40% mets, but – Overdetection? • FUTURE: Age-adjusted PSA, PSA velocity, PCA-3 В©2007 RUSH University Medical Center PSA – may rise in presence of CAP • Drawbacks: – up to 30 percent of men with prostate cancer have a normal PSA – 75 percent of men with an high PSA blood test do not have prostate cancer – the PSA blood test cannot determine if the cancer is a slow-growing or aggressive cancer – Still is the best test we have В©2007 RUSH University Medical Center Why do we screen? To Avoid An Advanced Stage At Diagnosis: Early detection is the goal for any cancers Men Assuming Responsibility for Their Health PSA DRE В©2007 RUSH University Medical Center How does early detection help? • Survival rate at 5 years is 100.0% for those whose cancer is still just in the prostate gland (localized). • Survival rate at 5 years for those whose cancer has spread beyond the gland (late diagnosis) is only 33.5% В©2007 RUSH University Medical Center Screening • American Urological Association screening recommendations: • Digital Rectal Examination & PSA 1.All males over the age of 40 – annually – ?45 or 50 2.All African American males over age of 40 – annually 3.All pts with family hx (1st degree relative) starting at age 40 – annually • ACS: 50 – 45 if 1st degree or AA В©2007 RUSH University Medical Center Screening • If PSA or Digital Rectal Examination is abnormal, then patient needs a prostate biopsy В©2007 RUSH University Medical Center В©2007 RUSH University Medical Center В©2007 RUSH University Medical Center Staging of Prostate Cancer • • • • • • • PSA Digital Rectal Exam Trans Rectal Ultrasound Gleason Score Bone Scan +/- CT scan or MRI Biopsy and TNM staging system – Tumor, Nodes, Metastases В©2007 RUSH University Medical Center Stage I or Stage A Prostate Cancer • Stage I cancer is found only in the prostate and usually grows slowly В©2007 RUSH University Medical Center Stage II or Stage B Prostate Cancer • Stage II cancer has not spread beyond the prostate gland, but involves more than one part of the prostate, and may tend to grow more quickly В©2007 RUSH University Medical Center Stage III or Stage C Prostate Cancer • Stage III cancer has spread beyond the outer layer of the prostate into nearby tissues or to the seminal vesicles, the glands that help produce semen В©2007 RUSH University Medical Center Stage IV or Stage D Prostate Cancer • Stage IV cancer has spread to other areas of the body such as the bladder, rectum, bone, liver, lungs, or lymph nodes В©2007 RUSH University Medical Center Biopsy Results – Gleason Score • Gleason Score = sum of the two most common histologic patterns (primary and secondary) • Range: Gleason 1(well differentiated) – 5 (poorly differentiated) • The higher the Gleason Score, the more poorly differentiated the cancer (more aggressive) • i.e. Gleason 3 + 3 = 6 • Gleason 4 + 3 = 7 • Gleason 5 + 4 = 9 • Gleason 3 + 4 в‰ 4 + 3 В©2007 RUSH University Medical Center Gleason Score • Gleason Score = sum of the two most common histologic patterns (primary and secondary) • Range: Gleason 1(well differentiated) – 5 (poorly differentiated) • The higher the Gleason Score, the more poorly differentiated the cancer (more aggressive) • i.e. Gleason 3 + 3 = 6 • Gleason 4 + 3 = 7 • Gleason 5 + 4 = 9 • Gleason 3 + 4 в‰ 4 + 3 В©2007 RUSH University Medical Center Risk Groups Low Intermediate High Stage ≤ T2a T2b T2c or > Gleason Score ≤6 7 8-10 PSA < 10 >10 & < 20 ≥ 20 В©2007 RUSH University Medical Center Treatment Options Dependent upon…… • Stage of disease • Patient’s age and health • Patient’s personal preference В©2007 RUSH University Medical Center Treatment Options (early diagnosis) п‚§ Watchful waiting пѓ Active Surveillance п‚§ Radiation Therapy п‚§ External Beam Radiation Therapy п‚§ Brachytherapy (Radioactive seeds) п‚§ HDR п‚§ Cryosurgery (Freezing prostate) п‚§ Surgery (Radical Prostatectomy) п‚§ Open Surgery п‚§ Conventional Laparoscopic Surgery п‚§ da Vinciв„ў Prostatectomy (Robotic-Assisted Laparoscopic Surgery) В©2007 RUSH University Medical Center Active Surveillance • Appropriate in patients: – with a less than 10 year life expectancy – GS ≤ 6 – Non palpable disease • DRE, serum PSA q 6 months • Patients become symptomatic and require treatment 30-50% of time В©2007 RUSH University Medical Center Treatment Options (early diagnosis) п‚§ Watchful waiting пѓ Active Surveillance п‚§ Radiation Therapy п‚§ External Beam Radiation Therapy п‚§ Brachytherapy (Radioactive seeds) п‚§ HDR п‚§ Cryosurgery (Freezing prostate) п‚§ Surgery (Radical Prostatectomy) п‚§ Open Surgery п‚§ Conventional Laparoscopic Surgery п‚§ da Vinciв„ў Prostatectomy (Robotic-Assisted Laparoscopic Surgery) В©2007 RUSH University Medical Center
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