1. Prostate Cancer Screening in 2013: Reports of its Death Are Greatly Exaggerated Norm D. Smith, M.D. Associate Professor Co-Director Urologic Oncology University of Chicago

2. United States Preventive Services Task Force (USPSTF) USPSTF Warns Against Blood Test For Prostate Cancer USPSTF Warns Against Blood Test For Prostate Cancer ABC World News - “An earthquake today in the debate over men and prostate cancer” ABC World News - “An earthquake today in the debate over men and prostate cancer” ABC World News ABC World News New York Times "PSA does not save lives, but results in needless medical procedures that have left tens of thousands of men impotent, incontinent or both” New York Times "PSA does not save lives, but results in needless medical procedures that have left tens of thousands of men impotent, incontinent or both” New York Times New York Times

3. United States Preventive Services Task Force (USPSTF) Los Angeles Times -16-member panel determined whether widespread PSA testing saves enough lives to justify the considerable medical fallout Los Angeles Times -16-member panel determined whether widespread PSA testing saves enough lives to justify the considerable medical fallout Los Angeles Times Los Angeles Times HealthDay - the task force studied "five trials, the two largest done in Europe and in the United States... found no reduction in deaths due to prostate cancer among men of all ages in the study who underwent PSA testing” HealthDay - the task force studied "five trials, the two largest done in Europe and in the United States... found no reduction in deaths due to prostate cancer among men of all ages in the study who underwent PSA testing” HealthDay

4. United States Preventive Services Task Force (USPSTF) New York Times - Aetna and Kaiser Permanente said it was unclear whether they would continue paying for the test… United Healthcare and WellPoint said they would continue coverage New York Times - Aetna and Kaiser Permanente said it was unclear whether they would continue paying for the test… United Healthcare and WellPoint said they would continue coverage New York Times New York Times GQ Medicare "is required under a 2008 law to cover the PSA test annually for beneficiaries 50 years old and older. Presumably it would take an act of Congress to undo that coverage requirement. Medicaid coverage of the PSA test is a state by state decision." GQ Medicare "is required under a 2008 law to cover the PSA test annually for beneficiaries 50 years old and older. Presumably it would take an act of Congress to undo that coverage requirement. Medicaid coverage of the PSA test is a state by state decision." GQ

5. United States Preventive Services Task Force (USPSTF) No Urologists No Urologists Grade D recommendation against PSA- based screening for prostate cancer Grade D recommendation against PSA- based screening for prostate cancer “moderate or high certainty that the service has no net benefit… harms outweigh the benefits” “moderate or high certainty that the service has no net benefit… harms outweigh the benefits” Discourage PSA screening Discourage PSA screening

6. Prostate Cancer Screening Studies - 2009

7. Prostate Test Found to Save Few Lives (New York Times, March 2009) Last week, two major studies from the United States and Europe found that P.S.A. testing — the annual blood test used to screen men for prostate cancer — saves few if any lives, while exposing patients to aggressive and unnecessary treatments that can leave them impotent and incontinent P.S.A.prostate cancer P.S.A.prostate cancer

8. Prostate-Specific Antigen Best Practice Statement: 2009 Update (American Urological Association) http://www.auanet.org/content/guidelines-and- quality-care/clinical-guidelines/main- reports/psa09.pdf http://www.auanet.org/content/guidelines-and- quality-care/clinical-guidelines/main- reports/psa09.pdf http://www.auanet.org/content/guidelines-and- quality-care/clinical-guidelines/main- reports/psa09.pdf

19. PSA Biopsy Thresholds (4.0 versus 2.5 ng/ml)

20.  0.9 Results Age < 60 0 0.2 0.4 0.6 0.8 1 00.20.40.60.81 1-specificity sensitivity  2.6.69 .86 p = 0.0001  1.4  4.1  1.4  6.1  0.9  2.6  6.1  4.1 adjusted for bias unadjusted

21. Results Age > 60 0 0.2 0.4 0.6 0.8 1 00.20.40.60.81 sensitivity 1-specificity adjusted for bias unadjusted  4.1  1.1  2.1  6.1  10.1  1.1  2.1  4.1  6.1  10.1.62 .72 p = 0.008

22. T1c Patients with RRP by PSA at Diagnosis ( PSA Follow-up Study) 2.6-4.0 4.1-6.0 6.1-9.9 > 10 Number of Months 120100806040200 Probability of No PSA Progression 1.0.9.8.7.6.5.4.3.2.1 0.0 PSA correlates with 10-year progression- free survival rates

23. Freedland SJ. J Urol 174: 1276-81, 2005

24. Age to Start PSA Screening

25. Baltimore Longitudinal Study on Aging Median PSA level: Median PSA level: Age 40-49 = 0.6 ng/ml Age 40-49 = 0.6 ng/ml Age 50-59 = 0.7 ng/ml Age 50-59 = 0.7 ng/ml 3-fold higher risk of prostate cancer within 10-25 years if PSA > median for age group 3-fold higher risk of prostate cancer within 10-25 years if PSA > median for age group Fang et al. Urology, 58: 411, 2001.

26. Age- Specific Median PSA Age GroupMedian PSA (ng/ml) 40s0.7 50s0.9 60s1.3 70s1.7

27. If baseline PSA is > median for age group, the risk of cancer is 12- to 22-fold higher

28. Odds Ratio of Subsequent Prostate Cancer Diagnosis Loeb S, Roehl KA, Antenor JA, Catalona WJ, Suarez BK, Nadler RB. Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer in men younger than 60 years old. Urology. 2006;67(2):316-20. VariableOR95% CI Any baseline PSA >0.7 ng/mL for men 40– 49 yr 30.94.2–229.4 Baseline PSA between 0.7 and 2.5 ng/mL for men 40–49 yr 14.61.9–113.7 Any baseline PSA >0.9 ng/mL for men 50– 59 yr 13.29.9–17.4 Baseline PSA between 0.9 and 2.5 ng/mL for men 50–59 yr 7.65.7–10.2 Suspicious vs. negative DRE4.93.9–6.1 Age in 50s vs. 40s2.31.6–3.5 African-American heritage1.20.9–1.5 Family history1.061.02–1.11

30. PSA Kinetic Parameters PSA Velocity PSA Velocity absolute change in PSA per year absolute change in PSA per year Independent of baseline PSA value Independent of baseline PSA value Better for diagnosis Better for diagnosis PSA Doubling Time PSA Doubling Time Time it takes PSA value to double Time it takes PSA value to double A function of baseline PSA (the higher the baseline, the longer it takes to double) A function of baseline PSA (the higher the baseline, the longer it takes to double) Not as useful for diagnosis Not as useful for diagnosis

31. Median PSAV (ng/ml/yr) Cancer0.8 Non-Cancer Biopsy 0.1 No Biopsy0.1 PSA Velocity in PSA Study P<0.0001

32. PSA Velocity for Detecting Life- Threatening PCa when Still Curable For men with a consistent PSAV of >0.35 ng/ml/year, there is more than a 5-fold increased risk of PCa death in next 2-3 decades For men with a consistent PSAV of >0.35 ng/ml/year, there is more than a 5-fold increased risk of PCa death in next 2-3 decades Recommended to begin PSA testing at age 40 to acquire reliable PSAV data Recommended to begin PSA testing at age 40 to acquire reliable PSAV data Carter HB et al JNCI 2006;98:1521-7

33. OR (95% CI) p-value PSAV > 0.46.06 (5.19-7.08)<0.0001 Total PSA (per unit) 1.08 (1.05-1.10)<0.0001 Age (per year)1.04 (1.03-1.05)<0.0001 AA vs Caucasian1.57 (1.19-2.07)0.002 Family history1.25 (1.03-1.52)0.02 Multivariate analysis to predict prostate cancer detection AUC=0.80

35. American Cancer Society, Cancer Facts & Figures 2005

36. Example of National Mortality Rate Trends

37. Denmark

38. “The trends in prostate cancer mortality rates in examined countries suggest that PSA screening may be effective in reducing mortality from prostate cancer.” Example of WHO Global Mortality Rate Trends

39. Pattern A: Prostate Cancer Mortality Lower than before PSA Era

40. Pattern B: Prostate Cancer Mortality Decreasing but Still Higher than Before PSA Era

41. Pattern C: Prostate Cancer Rate Still Increasing Constantly (18 of 38 Countries Examined)

42. Take Home Messages for PSA Screening Initial PSA screening at age 40 Initial PSA screening at age 40 If PSA higher than median for age, annual screening at minimum (perhaps 6 months) If PSA higher than median for age, annual screening at minimum (perhaps 6 months) Annual PSA screening at 40 for African- Americans and men with family history Annual PSA screening at 40 for African- Americans and men with family history Biopsy threshold 2.5 in men < 60 Biopsy threshold 2.5 in men < 60 Consider biopsy for PSA velocity > 0.35 Consider biopsy for PSA velocity > 0.35 PSA screening likely saves lives PSA screening likely saves lives