Prostate Cancer PDF

PROSTATE CANCER UĞUR BOYLU, M.D. Professor of Urology Istinye University, Faculty of Medicine, Department of Urology Liv Hospital Ulus, Istanbul Carcinoma of Prostate Most common cancer in United States with exception of skin cancer I...

PROSTATE CANCER UĞUR BOYLU, M.D. Professor of Urology Istinye University, Faculty of Medicine, Department of Urology Liv Hospital Ulus, Istanbul Carcinoma of Prostate Most common cancer in United States with exception of skin cancer Increases in new cases by 50% between 1980 and 1990 New cases in 2009 – 192,280 (Est.), 80 % early disease Deaths – 27,360 (Est.) Increasing number of “non-lethal” tumors being diagnosed 1 in 6 will be diagnosed, 1 in 35 will die from it. (10% of cancer related deaths in men.) Survival Rates – Prostate Cancer 5-year relative survival rate nearly 100% 10-year relative survival rate is 91% 15 year relative survival rate is 76% Risk Factors for Prostate Cancer Age – Rare before 40; 65% over the age of 65 Race - More common in African-American men; more likely diagnosed at advanced stage; 2x more likely to die of the disease; less common in Asian-American and Hispanic-American men than non-Hispanic whites. Family History - 1st degree relatives, father, brother Nationality - North America and NW Europe vs Asia, Africa, Central and South America Genetics – BRCA1 and BRCA2 increase risk, but account for very small percentage of prostate cancer Obesity, Diet, Exercise, prostatitis, STDs, Vasectomy – not much effect, BUT……. Risk Factors for Prostate Cancer Claimed by some studies Diet Red meat, high fat dairy products Fruits, vegetables, grains Exercise and maintaining healthy weight may decrease the risk Chemoprevention - Other The Selenium and Vitamin E cancer Prevention Trial was a large randomized placebo-controlled trial of Vitamin E and selenium, alone or in combination. It failed to demonstrate that these drugs reduce prostate cancer in relatively healthy men. Lippman SM, Klein EA, Goodman PJ, et al.: Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301 (1): 39-51, 2009 Early detection and screening Digital rectal exam – Feel for nodules PSA – How high? Transrectal ultrasound – not for screening First two tests are convenient and inexpensive, but consequences may not be PSA and Prostate Cancer Risk When prostate cancer develops, the PSA level usually goes above 4. Still, a level below 4 does not mean that cancer isn't present -- about 15% of men with a PSA below 4 will have prostate cancer on biopsy. Men with a PSA level in the borderline range between 4 and 10, have about a 1 in 4 chance of having prostate cancer. If the PSA is more than 10, the chance of having prostate cancer is over 50% Confounding Factors for PSA Increase – BPH – Age – Prostatitis – Ejaculation Decrease – Finasteride, dutasteride – Some herbal mixtures – Obesity Under investigation: PSA Density, PSA Velocity, % free PSA PSA Density - Normalized to prostate volume PSA Velocity - Change in PSA over time (e.g., more than 15% per year) Free PSA/Total PSA - lower ratio suggests cancer, since more free PSA from normal prostate is degradated (< 10% - biopsy) Presenting Symptoms of Prostate Cancer Decreased urinary stream Urinary frequency Hematuria Bone pain LE numbness or weakness Badder/bowel incontinence PSA Levels and Their Predictive Value for Diagnosis Other conditions besides prostate cancer can increase PSA levels infection inflammation benign growths 2004 Study of men: PSA never above 4ng/ml; no abnormal rectal exam Percent with prostate cancer PSA level (ng/ml) 26% 3.1 to 4.0 24% 2.1 to 3.0 17% 1.1 to 2.0 10%.6 to 1.0 7% less than.5 In those with cancer and low PSA levels, 12.5% had aggressive, rapidly multiplying high-grade tumors likely to spread. Sources: Cooner WH, Mosley BR, Rutherford CL Dr. et al. Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal examination and prostate specific antigen. J Urol. 1990;143:1146-52. Cited in Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, et al. Krumholtz JS, Carvalhal GF, Ramos CG, et al. Prostate-specific antigen cutoff of 2.6 ng/mL for prostate cancer screening is associated with favorable pathologic tumor features. Urology. 2002;60:469-473. Effect of Early Diagnosis Unknown: In areas where there is aggressive screening, the incidence in higher than where there is not; the death rate from prostate cancer is similar Randomized trials to test screening underway Conclusion: – Do not screen over age 70, or if life expectancy < 10 years – Do not screen under age 60, unless strong family history – Recognize limitations age 60-70 Prostate Cancer Survival Related to – Stage – Grade – Extent of tumor at diagnosis Local disease - Median Survival > 5 years Metastatic disease Median Survival 1-3 years, but individuals may survive 10 or more years Establishing a Diagnosis of Prostate Cancer n DRE n PSA/PSA velocity/percent-free PSA n Transrectal U/S n U/S- guided biopsy Evaluation of Abnormal PSA or Prostate Mass Ultrasound guided needle biopsies (6-12) If positive, Gleeson score (2 predominant histologies). Range - 2 (1+1) to 10 (5+5) – 2-4 - Best – 5,6 - Intermediate – 7-10 - Worse PSA < 10, rarely have detectable metastatic disease Staging and Prognostic Factors n TNM staging system n Prognostic Factors n Gleason grading n DNA analysis by flow cytometry n PSA level n Predictive models for organ-confined versus non- organ confined disease Staging Prostate Cancer Abdominal and pelvic CT scans Chest x-ray Bone scan LFT’s Serum PSA and acid phosphatase Staging Prostate Cancer Stage I - T1a and grade 1 (Incidental, early) Stage II - – T1a and Grade 2-4; T1b,c (By biopsy only) – T2 (Confined to Prostate) Stage III - T3 (Through prostate capsule) Stage IV - T4 (Invades adjacent structures), N1-3, M1 Recurrence Risk for Clinically Localized Prostate Cancer n Low Risk: n T1-T2a and Gleason score 2-6 and PSA < 10 ng/ml n Intermediate Risk: n T2b-T2c or Gleason score 7 or PSA 10-20 n High Risk: n T3a or Gleason score 8-10 or PSA > 20 n Very High Risk: n T3b-T4(locally advanced) Treatment Decisions for Clinically Localized Prostate Cancer n Based on recurrence risk (Low, intermediate, or high) and n Life expectancy ( 10 years). Prostate - Goals of Therapy Primary Therapy – T1a - Except in very young (< 60), follow with no therapy – T1b, T1c, T2 - radical prostatectomy or high dose radiation therapy. (May also observe if low-grade) – T3 (Stage III) - Usually treated with radiation therapy – Metastatic - Treat when symptoms. In high risk disease, may add hormonal therapy Radical Retropubic Prostatectomy (RRP) Ø “Nerve Sparing” procedure developed by Walsh consisted of modified surgical technique to control blood and enhance visibility within surgical site. Ø Allowed for the identification and potential preservation of the nerves that control erectile function (potency). Ø Two neurovascular bundles on either side of the prostate that control erectile function. Radiation Therapy (RT) Ø High-Powered X-Rays that damage DNA and kill prostate cancer cells. 1. External Beam Radiation Therapy (EBRT): X- rays aimed at prostate. 2. Brachytherapy: Radioactive seed implants into prostate. Watchful Waiting Ø A.K.A. observation, expectant therapy or deferred therapy. Ø Diagnosis of an early-stage (T1-T2), low-grade tumor. Ø No medical treatment is provided. Ø Patient receives regular follow-up to monitor tumor. Treatment of Symptomatic Metastatic Disease 1. Hormonal Therapy - initial therapy for locally advanced or metastatic disease – Orchiectomy – Estrogens (No longer used) – LHRH analogs (+/- anti-androgens) – Antiandrogens + finasteride – Second line therapies consist of one of therapies not used before, e.g., anti-androgens if used only LHRH analogs Conclusions Risk factors are age, family history, race, and possibly diet and exercise Overall survival excellent (many years) Early detection can find localized cancer, but survival benefits still uncertain Treatment depends on grade, extent and location of disease Surgery and radiation are equivalent therapeutic tools for localized prostate cancer Hormonal therapy is effective for metastatic prostate cancer Hormone refractory prostate cancer responds to chemotherapy, with occasional long term improvement.