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Now the World Knows We Need a Better Mousetrap (October
2003)
Ever since the NEJM
publication in July on "Effect of Verification Bias on Screening for
Prostate Cancer by Measurement of Prostate-Specific Antigen", the news
media has heralded the deficiency of the PSA test in prostate cancer
detection. Seattle Times, July 30: "...PSA test - probably misses more
than 80% of the cancers in men younger than 60 and almost two-thirds of
the cancers in older men." [!] Unfortunately, until (and if) rapid,
high-throughput throughput serum proteomics or other new approaches come
to our rescue, we are left with rearranging the various permutations of
the "PSA" molecule to gain greater test specificity.
A claim of greater test
specificity was recently made by Mikolajczyk, Beckman Coulter, Inc., in
his presentation at the Annual Meeting of the American Association for
Cancer Research (published in Keio Journal of Medicine, 52(2):86-91, June
2003). His Beckman group "have developed highly specific and sensitive
research immunoassays for BPSA [associated with BPH] and the different
forms of proPSA.
A bit of background
biology: In normal prostate glands proPSA is secreted into the glandular
lumen where seven amino acids are cleaved to create active PSA, some of
which gains access to the circulation where it is immediately complexed.
In cancer, presumable because of disruption of the basement membrane, the
proPSA enters the circulation directly and, by avoiding entering the
lumen, escapes the enzymatic conversion into active PSA. The result is
greater quantities of proPSA in the serum. The measurement of this proPSA
is the basis of their test, which aims at better detection of the prostate
cancer, present in 20 - 30% of men in the 2 - 4 ng/ml PSA range.
Results: When the proPSA
test was set at a sensitivity of 90% and applied to men within the PSA
range of 2.5-4 ng/ml "the specificity for the proPSA was 25% compared to
10% for %free PSA and complexed PSA (P=<0.001). And this increased
specificity was maintained in the PSA range of 4 - 10 ng/ml.
Bottom Line:
Any increase in the specificity of "PSA" testing will help to avoid
negative biopsies.
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