1. A PRACTICAL GUIDE TO PSA SCREENING Kendall Itoku, MD St. Louis Urological Surgeons

2. OBJECTIVES GENERAL BACKGROUND INFORMATION AND HISTORY OF PSA SCREENING FOR PROSTATE CANCER GENERAL BACKGROUND INFORMATION AND HISTORY OF PSA SCREENING FOR PROSTATE CANCER ADDRESS THE CONTROVERSY ON PSA SCREENING: SHOULD SCREENING FOR PROSTATE CANCER BE DONE? ADDRESS THE CONTROVERSY ON PSA SCREENING: SHOULD SCREENING FOR PROSTATE CANCER BE DONE? PRACTICAL GUIDELINES FOR THE USE OF PSA SCREENING FOR YOUR PATIENTS PRACTICAL GUIDELINES FOR THE USE OF PSA SCREENING FOR YOUR PATIENTS

3. PSA SCREENING SHOULD BE DONE ANNUALLY FOR EVERY MAN OVER 40 VS PSA SCREENING IS THE WORST PUBLIC HEALTH DISASTER IN HISTORY AND SHOULD NOT BE DONE

5. Prostate Specific Antigen (PSA) Background Information PSA is a glycoprotein produced by the epithelial cells that line the ducts of the prostate gland. PSA is a glycoprotein produced by the epithelial cells that line the ducts of the prostate gland. Discovered in 1970 by Dr. Richard Ablin, University of Arizona, Tucson. Discovered in 1970 by Dr. Richard Ablin, University of Arizona, Tucson. Functions to help liquify semen. Functions to help liquify semen. Disruption of normal prostate architecture by inflammation, infection, or cancer causes more PSA to enter circulation. Disruption of normal prostate architecture by inflammation, infection, or cancer causes more PSA to enter circulation. DRE, ejaculation, vigorous sex does NOT significantly alter PSA. Nor does dialysis. DRE, ejaculation, vigorous sex does NOT significantly alter PSA. Nor does dialysis.

6. Prostate Cancer Background Info Prostate cancer is the most common noncutaneous cancer in the US. Prostate cancer is the most common noncutaneous cancer in the US. Prostate cancer is the 2 nd leading cause of male cancer mortality. (28,660 deaths 2008). Prostate cancer is the 2 nd leading cause of male cancer mortality. (28,660 deaths 2008). Lifetime risk of prostate cancer is estimated at 1/6. (16%) Lifetime death risk 3.4%. Lifetime risk of prostate cancer is estimated at 1/6. (16%) Lifetime death risk 3.4%. Prostate cancer risk is elevated in African American men. Prostate cancer risk is elevated in African American men. Prostate cancer risk is elevated in men whose father or brother have prostate cancer. Prostate cancer risk is elevated in men whose father or brother have prostate cancer.

7. Prostate Cancer Background Info Since the 1990’s (when PSA screening came into wide usage) Prostate cancer deaths down 4.1% per year, 1996 to 2006. Prostate cancer deaths down 4.1% per year, 1996 to 2006. Lower stage at time of diagnosis. (1988 19.2% with locally advanced cancer. 1998 4.4% with locally advanced cancer.) Lower stage at time of diagnosis. (1988 19.2% with locally advanced cancer. 1998 4.4% with locally advanced cancer.)

8. PSA Testing is Currently Used for: Evaluation of men at risk for prostate cancer. Evaluation of men at risk for prostate cancer. Aid in early detection of prostate cancer. Aid in early detection of prostate cancer. Pretreatment staging and risk assessment for men with prostate cancer. Pretreatment staging and risk assessment for men with prostate cancer. Monitoring post treatment. Monitoring post treatment. Guide management and treatment of men who have a recurrence of prostate cancer. Guide management and treatment of men who have a recurrence of prostate cancer.

9. American Urological Association Recommendations (Revised in 2009) A baseline PSA should be done on all men starting at age 40. A baseline PSA should be done on all men starting at age 40. All men whose life expectancy is greater than 10 years should be screened. All men whose life expectancy is greater than 10 years should be screened. Prior to PSA screening, risks and benefits should be discussed. Prior to PSA screening, risks and benefits should be discussed. No prescribed cutoff PSA level should trigger a biopsy. No prescribed cutoff PSA level should trigger a biopsy.

10. PSA Screening Recommendations from other Organizations American Cancer Society (ACS): Age 50 for average risk, 40 for high risk American Cancer Society (ACS): Age 50 for average risk, 40 for high risk Centers for Disease Control and Prevention (CDC): Insufficient evidence to determine whether benefits outweigh harms Centers for Disease Control and Prevention (CDC): Insufficient evidence to determine whether benefits outweigh harms US Preventive Services Task Force (USPSTF): Not in men 75 or older, or those expected to live less than 10 years, otherwise insufficient evidence to determine benefit. US Preventive Services Task Force (USPSTF): Not in men 75 or older, or those expected to live less than 10 years, otherwise insufficient evidence to determine benefit. American College of Preventive Medicine (ACPM): Questionable in elderly men with other chronic illnesses and with life expectancies fewer than 10 years. American College of Preventive Medicine (ACPM): Questionable in elderly men with other chronic illnesses and with life expectancies fewer than 10 years. Institute for Clinical Systems Improvement (ICSI): Not enough evidence to clearly determine whether early detection and treatment saves lives. Institute for Clinical Systems Improvement (ICSI): Not enough evidence to clearly determine whether early detection and treatment saves lives.

11. PROS PSA Screening can help detect prostate cancer early. PSA Screening can help detect prostate cancer early. Prostate cancer is easier to treat and more likely to be cured at an early stage. Prostate cancer is easier to treat and more likely to be cured at an early stage. PSA testing can be done with a simple, widely available blood test. PSA testing can be done with a simple, widely available blood test.

12. CONS Most prostate cancers are slow growing and never metastasize. Most prostate cancers are slow growing and never metastasize. Treatment for prostate cancer has risks and side effects including incontinence, ED, chronic bowel dysfunction. Treatment for prostate cancer has risks and side effects including incontinence, ED, chronic bowel dysfunction. PSA testing can be inaccurate with high false positives and also false negatives. PSA testing can be inaccurate with high false positives and also false negatives. PSA testing leads to invasive follow up tests. PSA testing leads to invasive follow up tests.

13. Prostate Biopsy Will “miss” the cancer 25% of the time. Will “miss” the cancer 25% of the time. 1-4% Risk of significant bleeding or infection. 1-4% Risk of significant bleeding or infection.

15. DRE 10% of patients with prostate cancer have a normal PSA. 10% of patients with prostate cancer have a normal PSA. DRE can detect other diseases such as rectal cancer, hemorrhoids, fissures. DRE can detect other diseases such as rectal cancer, hemorrhoids, fissures. Several controlled studies have indicated that DRE combined with PSA increases accuracy of screening. Several controlled studies have indicated that DRE combined with PSA increases accuracy of screening. However, fear of DRE may prevent a man from undergoing screening. However, fear of DRE may prevent a man from undergoing screening.

17. Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) 76,693 men, randomized to get annual psa and DRE for 6 years or “usual care”. 76,693 men, randomized to get annual psa and DRE for 6 years or “usual care”. PSA level to trigger bx, 4.0 PSA level to trigger bx, 4.0 11.5 year follow up preliminary results show 22% more prostate cancer in study group vs control group. But no decrease in prostate cancer related mortality (92 deaths study group vs 82 deaths control). 11.5 year follow up preliminary results show 22% more prostate cancer in study group vs control group. But no decrease in prostate cancer related mortality (92 deaths study group vs 82 deaths control).

18. European Randomized Study of Screening for Prostate Cancer (ERSPC) 182,000 men randomized to PSA screening every 4 years or control group. 182,000 men randomized to PSA screening every 4 years or control group. PSA level to trigger bx, 3.0 PSA level to trigger bx, 3.0 At 9 years, 20% reduction in prostate cancer deaths in the study group. (214 vs 326) At 9 years, 20% reduction in prostate cancer deaths in the study group. (214 vs 326)

19. Prostate Cancer Prevention Trial 2950 healthy men, chemoprevention trial. 2950 healthy men, chemoprevention trial. Randomized to finasteride or placebo. Randomized to finasteride or placebo. 7 year follow up, yearly prostate bx. 7 year follow up, yearly prostate bx. Prostate cancer in 6.6%, psa <0.5. Prostate cancer in 6.6%, psa <0.5. Prostate cancer in 26.9%, psa 3.1 to 4.0. Prostate cancer in 26.9%, psa 3.1 to 4.0. Showed reduction in prostate cancer by 24% with finasteride. Showed reduction in prostate cancer by 24% with finasteride.

20. Reminder: PSA levels are elevated with prostatitis, UTI, instrumentation. PSA levels are elevated with prostatitis, UTI, instrumentation. Larger prostate gland will have a higher PSA. Larger prostate gland will have a higher PSA. PSA levels are lowered by 5 alpha reductase inhibitors. (multiply by 2) PSA levels are lowered by 5 alpha reductase inhibitors. (multiply by 2) PSA levels are not significantly affected by sex or DRE. PSA levels are not significantly affected by sex or DRE.

21. Tools to increase accuracy of PSA screening. Age specific normal ranges: <50-2.5, <60-3.5, <70 4.5, <80-6.5 Age specific normal ranges: <50-2.5, <60-3.5, <70 4.5, <80-6.5 PSA velocity: 0.75 increase per year PSA velocity: 0.75 increase per year Free/Total PSA ratio: 25% or greater is “good” Free/Total PSA ratio: 25% or greater is “good” PSA density (PSA/gland volume): <.37ng/cc is “good”. Requires TRUS. PSA density (PSA/gland volume): <.37ng/cc is “good”. Requires TRUS.

22. Premises for My PSA Screening Practical Guidelines Prostate cancer is the most common cancer in men. (2010 estimates 217,730 new cases, 32,000 deaths) Prostate cancer is the most common cancer in men. (2010 estimates 217,730 new cases, 32,000 deaths) Early stage, localized prostate cancer is “cured” over 90% of the time. Early stage, localized prostate cancer is “cured” over 90% of the time. Advanced prostate cancer has significant morbidity, including bone pain and fractures, bleeding, anemia, ureteral obstruction. Advanced prostate cancer has significant morbidity, including bone pain and fractures, bleeding, anemia, ureteral obstruction. PSA screening has and will continue to reduce the number of deaths from prostate cancer. PSA screening has and will continue to reduce the number of deaths from prostate cancer. Overdetection of prostate cancer is real, but justifiable, temporary, and modified by judgment in screening. Overdetection of prostate cancer is real, but justifiable, temporary, and modified by judgment in screening. Younger men are most likely to benefit from screening. Younger men are most likely to benefit from screening.

23. My Practical Guide to PSA Screening Discussion of risks and benefits before screening. Discussion of risks and benefits before screening. Both DRE and PSA (unless pt refuses DRE). Both DRE and PSA (unless pt refuses DRE). First screening at age 40. If psa is less than 1, every 2-4 years till age 50. First screening at age 40. If psa is less than 1, every 2-4 years till age 50. Yearly screening above age 50. Yearly screening above age 50. High risk men absolutely should be screened early and often. (African American, Family Hx) High risk men absolutely should be screened early and often. (African American, Family Hx) Age specific ranges for PSA threshold utilized. (<50-2.5, <60- 3.5,<70-4.5, <80-6.5). Age specific ranges for PSA threshold utilized. (<50-2.5, <60- 3.5,<70-4.5, <80-6.5). PSA velocity- 1 point in 1 year. PSA velocity- 1 point in 1 year. Discuss not screening in men over 80yo or those with life expectancy less than 10 years. (Don’t screen if you won’t treat.) Discuss not screening in men over 80yo or those with life expectancy less than 10 years. (Don’t screen if you won’t treat.)

24. My Guidelines for Screening after Negative Biopsy Repeat PSA and Free PSA in 6 months. If stable, resume annual screening. Repeat PSA and Free PSA in 6 months. If stable, resume annual screening. Repeat Biopsy based on PSA velocity. (If PSA rises by 1 point in 1 year.) Repeat Biopsy based on PSA velocity. (If PSA rises by 1 point in 1 year.) If Free PSA is less than 7%, strongly consider repeat biopsy, or closer f/u (q 6 months). If Free PSA is less than 7%, strongly consider repeat biopsy, or closer f/u (q 6 months). Atypia and PIN are difficult judgment calls. Low threshold for repeat biopsy within 6 months. Atypia and PIN are difficult judgment calls. Low threshold for repeat biopsy within 6 months.

26. Summary No consensus No consensus Plenty of evidence that screening is effective and justifiable Plenty of evidence that screening is effective and justifiable Not screening is hard to defend. Not screening is hard to defend. Need reliable indicator to identify clinically insignificant prostate cancer. Need reliable indicator to identify clinically insignificant prostate cancer. Use common sense and good clinical judgment. Use common sense and good clinical judgment.