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Conrad Notes
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PROSTATE SCREENING REDUCES CANCER DEATHS
F. Labrie, MD, PhD, Laval University, Quebec City, Canada, described a dramatic decrease in prostate cancer deaths by screening 8,137 men. First visit included prostate-specific antigen (PSA) test and digital rectal examination (DRE). An abnormal PSA or positive DRE signalled use of transurethral echography (TRUS) and if needed, prostate biopsy for diagnosis of the clinically localized cancer. Compared with 38,056 nonscreened men, the reported prostate cancer deaths decreased from 48.7 per 100,000 men-years (control) to 15.0 per 100,000 (screened and treated). Remarks by the invited discussant point to a need for other statistical analyses.
Screening methodology Labrie and coworkers began the screening program in 1988, well before the potential was apparent. The original sample consisted of male voters from metropolitan Quebec City who registered in 1985. This list yielded 46,193 men between 45 and 80 years and available for screening.

Screening invitations were mailed by random selection to 30,956 (67%) men. An additional 992 men invited themselves and participated in the screening program. The remaining men served as nonscreened controls. Quebec Province records provided death certificate information for prostate cancer deaths covering Jan 1, 1989 through Dec 31, 1996.

A synopsis on subject assignment and compliance follows:

  Number of Men %Compliant %Noncompliant
Invited 30,956 23 77
Uninvited 15,237 94 6
As noted later in the discussion, possible selection bias could have occurred based on the low compliance (response) rate to the invitation for screening.

Prostate cancer screening consisted of:

  • First visit: PSA test and DRE;
                   TRUS if PSA > 3 ng/mL or positive DRE
  • Annual follow-up: PSA test for all;
                   TRUS if PSA > 3 ng/mL or increased >20%
                   or >10% above expected PSA (based on
                   prostate volume)
  • Treatment started if prostate biopsy positive
Results of screening This 8-year study showed only 5 prostate cancer deaths in the screened/treated group and 137 in the control group (p&60;0.01). Death rates expressed per 100,000 men-years were:
Group Number Death Rate
A - Invited & Screened 7,155 13.7
B - Uninvited & Not Screened 14,255 41.6
C - Invited & Not Screened 23,801 53.0
D - Uninvited & Screened 922 23.7
The estimated relative risks (RR) and related confidence intervals were:
Comparison GroupsRR95% Conf Interval
A vs B3.0*1.1-11.6
A vs C3.9**1.5-14.4
B vs C1.30.9-1.9
       ___
       * significant (p=0.02)
     ** highly significant (p<0.01)
Presenter recommendations Labrie advocates screening men with a strong family history of prostate cancer and African Americans starting at age 40 and others at 50. Use of 4 ng/mL PSA as the upper normal limit would have led to missing 13% of prostate cancers at first visit and 21% at follow-up visits. Therefore, the acceptable PSA level needs to be set at 3 ng/mL.
Some remarks of invited discussant P. Boyle, MD, European Institute of Oncology, Milan, Italy, saluted the investigators for undertaking the first randomized, prospective trial to examine PSA in prostate cancer screening. Recent developments in statistical methodology as related to disease screening merit review and consideration.

The discussant recommended using the statistical model developed by Cuzick et al (Stat Med 1997;16:1017) to adjust for noncompliance and contamination in randomized trials. Because the present study encountered a 23% compliance rate in the invited group, it was susceptible to selection bias. In Boyle's opinion, the data need analysis. (Labrie et al used the Cuzick model and found a 6% decrease in prostate cancer mortality after comparing invited and uninvited men on an intent-to-screen basis. Cancer specific deaths decreased between 54% and 100% after adjusting for noncompliance and contamination, respectively. This alternative statistical approach confirmed the originally reported results on screening and early treatment).

Another short-coming relates to the death certificate. Current research teams include a death committee for assigning causality to such primary outcome data. Boyle finds the report of Nystrom et al (J Med Screen 1996;3:85) applicable for controlling possible bias in examining death rate data. (Labrie considers the Quebec Province records to be a reliable cancer death registry for the invited and uninvited men followed in this prospective trial).

For professional correspondence, please contact Dr. Labrie by Fax at: (418) 654-2735 or by E-mail at: Fernand.Labrie@crchul.ulaval.ca

Eugene A. Conrad

Presented at the American Society of Clinical Oncology (ASCO) Meeting, May 16-19, 1998
Copyright © 1998 Conrad Group Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / June 1998
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