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Urologist H. Ballentine Carter, M.D., is startled by
the results of his own research. Carter and Patrick C. Walsh, M.D.,
together with investigators at the Baltimore Longitudinal Study of
Aging (BLSA), pioneered the idea of PSA velocity — the rate
at which PSA increases over time — as a way of predicting whether
a man has prostate cancer.
For as long as PSA has been in widespread
use as an early detection tool for prostate cancer, Carter, The Peter
Jay Sharp Foundation Scholar, has worried about the numbers. Nearly
two decades ago, he cautioned (and we reported it, in Prostate Cancer
Update, the predecessor of Discovery) that there were risks to locking
into specific cutoff numbers. Back then, the general belief was that
a prostate biopsy should be performed if a man’s PSA reached
the “magic number” of 4 ng/ml.
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But there is no
such complacency anymore. “We now know that there is virtually
no PSA below which a man can be reassured that a lethal prostate
cancer does not exist,” Carter says. “Now, the problem
of where to set the bar for biopsy is that there should not be
one absolute bar.” Instead, Carter believes, “it makes
much more sense to pay attention to what changes in PSA are telling
us about the presence of a harmful prostate cancer.”
Carter
and Walsh, working with colleagues at the BLSA, discovered PSA velocity
in 1992. They found that in men with PSA levels between 4 and 10,
a PSA velocity above 0.75ng/ml per year was a more accurate predictor
of prostate cancer than any absolute level of PSA. Recently, recognizing
that about 5 percent of men with PSA levels considered low — between
2 and 3 — have aggressive and potentially lethal cancers, Carter
worked with colleagues at the BLSA in hopes of finding more definitive
information.
The BLSA is one of the largest studies of aging in
the world. Since 1958, scientists have collected and stored blood
samples, at twoyear- intervals, of approximately 1,500 men. Using
these stored blood samples, scientists have measured PSA over decades
in men who did and did not develop prostate cancer, and in men who
had aggressive and mild cancer. Together with investigators at the
BLSA and at the Brady, Carter used PSA velocity to help determine
the probability of dying of prostate cancer over three decades. “We found that
when PSA levels were below 4 — about 10 to 15 years before
men were diagnosed with their prostate cancer — a PSA velocity
above 0.35 ng/ml per year was associated with a five-times greater
risk of prostate cancer death when compared to a PSA velocity of
less than 0.35ng/ml per year.” For example, over a 30-year
period, about half of the men with a yearly PSA velocity above 0.35ng/ml
died of prostate cancer, compared to only 8 percent of men with a
yearly PSA velocity lower than 0.35ng/ml. “I am not aware of
another test that can predict the likelihood of prostate cancer death
with this accuracy prior to the diagnosis of the disease,” says
Carter. He cautions that for the most accurate results using PSA
velocity, the interval between tests should be at least six months,
and testing should span a period of at least 18 months.
Given this
discovery, Carter recommends that all men — whether or not
they have a family history of prostate cancer, or are at increased
risk of developing the disease — should have a baseline PSA
test at age 40 — 10 years earlier than many doctors recommend.
Then, depending on their baseline level, men should be tested again
several times in their forties. “These early PSA tests can
be used later, when a man reaches his fifties and sixties, to determine
PSA velocity and the likelihood that a lethal prostate cancer is
present,” he says. |
