Prostate cancer detection
standards adopted by World Health Organization
BY GREG MILLER
The World Health
Organization (WHO) has designated two calibration
standards developed at Stanford as international
standards to be used to improve the reliability of blood
tests for prostate specific antigen (PSA), an important
indicator of prostate cancer.
The Stanford calibrators
are standardized samples of purified PSA that will be
used by doctors around the world to calibrate the assays
they use to determine blood levels of PSA. This
calibration will help ensure that PSA tests done at
different times or different places yield consistent
results.
PSA is an enzyme produced
by the healthy male prostate gland, explained Thomas
Stamey, MD, professor of urology and head of the research
team that developed the calibrators. However, in men with
prostate cancer, levels of the enzyme increase because
cancer cells also produce it. High levels of PSA in the
blood, therefore, indicate an increased likelihood of
cancer.
"In the United
States, 80 percent of all men diagnosed with prostate
cancer are diagnosed because of their PSA level,"
Stamey said.
As is the case for any
diagnostic tool, though, PSA levels are only useful if
the assays used to measure them are reliable.
When the first PSA assays
became available in the late 1980s, Stamey said, there
was no way to standardize assays made by different
manufacturers. Tests in his laboratory during this time
showed that different assays could give results that
differed by as much as 100 percent for the same blood
sample.
As a result PSA levels
measured in the same patient at different times could
vary substantially if different assays were used, even if
the patient's actual PSA levels did not change. Stamey
and his colleagues tackled this problem by working to
produce purified samples of PSA that could be used to
calibrate the assays and eliminate major discrepancies
among different brands.
Their task was complicated
because PSA comes in two forms, termed "free"
and "complexed." In men with prostate cancer,
90 percent of the PSA in the blood is in the complexed
form. This percentage is lower in men without cancer,
including men with a common but harmless enlargement of
the prostate called benign prostatic hyperplasia (BPH).
As a result, the makeup of
the PSA in the blood, in addition to the overall PSA
level, provides important information. Men with elevated
total PSA levels and a high percentage of complexed PSA
are more likely to have cancer than men whose PSA levels
are elevated by an increase in the free form of PSA -- a
condition indicative of BPH.
The makeup of the PSA in
the blood is typically determined by running two assays
-- one to measure the free PSA level and one to measure
the total (free plus complexed) PSA level. Therefore, two
calibrators were needed -- one for each assay.
Stamey's group developed
the two calibrators and presented them to the National
Committee for Clinical Laboratory Standards, the official
body that approves laboratory assays in the United
States. The calibrators were approved as the U.S.
national standard in 1997.
The same year, Stamey was
notified that the calibrators were among several
candidates under consideration by WHO for use as
worldwide standards. Each standard underwent extensive
evaluation, which included testing the stability of the
samples and their ability to withstand temperature
variations that might be encountered around the world.
The announcement that the
Stanford standards had been chosen was made last month in
Geneva, Switzerland at the 50th meeting of WHO's Expert
Committee on Biological Standardization. SR
|
