Transcript What is the evidence of benefits of PSA screening for prostate cancer?

What is the evidence of benefits
of PSA screening for prostate
cancer?
Outpatient Medicine
Objective
• Review the evidence concerning the effect
of PSA screening on prostate cancer
mortality (Question 1 of the USPTF report
on prostate cancer screening)
RCTs (and quasi-RCTs) of PSA
screening
• 1988 Quebec Prospective Randomized
Controlled Trial
• Norkopping, Sweden study
• ERSPC
• PLCO
Observational studies
• Canada
• Tyrol, Austria
• Olmsted County, Minnesota
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
1988 Quebec
• Results at 7 year follow up:
Compliance in treatment arm: 23%
Compliance in control arm: 93%
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
11 year follow up of Quebec study
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
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.
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 6th year of the study,
this is not a 15 year follow up for PSA screening
Norrkoping
• Comments
– No reported data comparing baseline
characteristics of screened vs control
– No reported data on crossover, compliance,
etc.
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
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.
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”
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.
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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.