1. What is the evidence of benefits of PSA screening for prostate cancer? Outpatient Medicine

2. Objective Review the evidence concerning the effect of PSA screening on prostate cancer mortality (Question 1 of the USPTF report on prostate cancer screening)

3. RCTs (and quasi-RCTs) of PSA screening 1988 Quebec Prospective Randomized Controlled Trial Norkopping, Sweden study ERSPC PLCO

4. Observational studies Canada Tyrol, Austria Olmsted County, Minnesota

5. 1988 Quebec Perspective Randomied Controlled Trial n = 46K men age 45-80 Randomized to an “invite for screening” group and a control group. Treatment group received PSA (ULN = 3.0) and DRE. If either abnormal patients received TRUS and sextent Bx

6. 1988 Quebec Results at 7 year follow up: Compliance in treatment arm: 23% Compliance in control arm: 93%

7. 1988 Quebec 11 year follow up: no difference according to intention (invitation) to screen. Among all screened individuals: 19 prostate cancer deaths / 100k Among non-screened: 53.4 deaths / 100k

8. 11 year follow up of Quebec study

9. 1988 Quebec Comments: –No comparison between the groups (invited vs. not invited) –No comparison between screened and unscreened groups –Inappropriate analysis of screened vs. unscreened rather than intention to screen

10. Norrkoping Sweden study n = 9026 men in Norrkoping, Sweden Patients in the screened group (SG, n = 1494) were given DREs in 1987 and 1990, as well as DRE + PSA in 1993 and 1996.

11. Norrkoping Results In SG 5.7% of patients were diagnosed with cancer, about ½ on the initial DRE in 1987. 56.5% of these cancers were localized at time of diagnosis. In the control group (CG), 3.8% were diagnosed with cancer, 27% of which were organ confined. NO DIFFERENCE IN SURVIVAL at 15 year follow up. Since PSA was not used until the 6 th year of the study, this is not a 15 year follow up for PSA screening

12. Norrkoping Comments –No reported data comparing baseline characteristics of screened vs control –No reported data on crossover, compliance, etc.

13. European Randomized Study of Screening for Prostate Cancer (ERSPC) Powered to detect a 25% reduction in prostate cancer mortality through screening. In 2006 data was assessed and the trial was continued

14. PLCO Trial N = 76,705 (38,350 screened) Screened group given annual PSA and DRE Compliance 89% 1.4% of men in the initial screening are were diagnosed, the majority with localized Mortality results pending. Patients enrolled from 1993 through 2001.

15. Population analyses In several Western countries including the US and Canada (34.1 to 28.3 deaths per 100k), prostate cancer mortality has decreased substantially since the early 1990s, when PSA screening was introduced. No one knows why this is –PSA screening –New therapies (anti-androgen therapy) –“attribution bias”

16. References Lin K, Lipsitz R, Miller T, Janakiraman S. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med. 2008;149:192-199. Labrie F, Candas B, et al. Screening decreases prostate cancer death: first analysis of the 1988 Quebec prospective randomized controlled trial. Prostate 1999;38:83-91. Labrie F, Candas B, et al. Screening decreases prostate cancer mortality: 11-year follow-up of the 1988 Quebec prospectve randomized controlled trial. Prostate 2004;59:311-318. Shroder. Screening for prostate cancer (PC) – an update on recent findings of the European randomized study of screening for prostate cancer (ERSPC). Urologic Oncology: Seminar and Original investigations 2008;26:533-541. Andriole GL et al. Prostate cancer screening in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial: findings from the initial screening round of a randomized trial. Journal of the national cancer institute 2005;97:433-438 Matteo LD, Matteo RD. Does testing for prostate-specific antigen contribute to declining prostate cancer mortality? Eur J Health Econom 2005;6:298-308. Oberaigner W et al. Reduction of prostate cancer mortality in Tyrol, Austria, after introduction of prostate-specific antigen testing. Am J Epidemiol. 2006;164:376-384. Bergstralh EJ et al. Population-based case-control study of PSA and DRE screening on prostate cancer mortality. Urology 2007;70:936-941. Hoffman RM. Screening for prostate cancer. UpToDate 2008. Accessed at www.uptodate.com on 12/6/2008.www.uptodate.com