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)  Watchful waiting пѓ Active Surveillance  Radiation Therapy  External Beam Radiation Therapy  Brachytherapy (Radioactive seeds)  HDR  Cryosurgery (Freezing prostate)  Surgery (Radical Prostatectomy)  Open Surgery  Conventional Laparoscopic Surgery  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)  Watchful waiting пѓ Active Surveillance  Radiation Therapy  External Beam Radiation Therapy  Brachytherapy (Radioactive seeds)  HDR  Cryosurgery (Freezing prostate)  Surgery (Radical Prostatectomy)  Open Surgery  Conventional Laparoscopic Surgery  da Vinciв„ў Prostatectomy (Robotic-Assisted Laparoscopic Surgery) В©2007 RUSH University Medical Center
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