It Was Medical Gospel, but It Wasn't True
May 30, 2004
By GINA KOLATA
FOUR nanograms of prostate specific antigen, or P.S.A., per
milliliter. For more than a decade, that has been the line
between normal and abnormal on a common annual blood test
used to screen for prostate cancer. Above four and you need
a biopsy of your prostate to look for cancer. Below four
and you go home.
But a new study, published last week in The New England
Journal of Medicine, showed that no matter how low his
P.S.A. level, a man could have prostate cancer.
In addition, it has long been known that men whose
prostates are enlarged, a normal consequence of aging, can
also have P.S.A. levels indistinguishable from those with
early prostate cancer.
So the question arises: How did four become the standard?
Even some leading urologists say they aren't sure.
Dr. E. David Crawford, the head of urologic oncology at the
University of Colorado Health Sciences Center, says a 1986
paper by a test maker, Hybritech (now part of Beckman
Coulter), proposed that number as the divider between
normal and abnormal P.S.A. levels.
But Dr. William Catalona, director of the prostate cancer
program at Northwestern University, said he was primarily
responsible for generating interest in using the P.S.A. as
a screening tool, first advocating its use at a 1988
meeting of the National Cancer Institute.
The test finds a protein, the prostate specific antigen,
that is released by prostate cells. Its levels go up
slightly early in the course of cancer, but also when the
prostate grows larger as a man ages. When cancer is
advanced, P.S.A. levels soar into the thousands, but the
test is looking at levels where only a biopsy could tell
whether or not cancer was present.
Dr. Catalona knew that, but, he said, given the seriousness
of the disease, "we were willing to pay that price."
Not everyone agreed. "I was howled down," at the cancer
institute, he said. "They were looking for something like a
pregnancy test; when it was positive you always had cancer
and when it was negative you never did."
Unfazed, Dr. Catalona began his own P.S.A. study with the
support of Hybritech, in which any test result over four
nanograms was considered abnormal. But that cutoff, the
same as in the Hybritech paper, was adopted "just sort of
arbitrarily" he said.
The usual sort of study to validate a screening test would
determine how likely the test is to miss a cancer that is
there and how many times it points to cancer when none is
present. But Dr. Catalona's test instead asked only how
often cancers were found and how the men fared after
In 1991, his findings appeared in The New England Journal
of Medicine. That, said Dr. Peter Albertsen, chief of
urology at the University of Connecticut, convinced
urologists. Four became the standard.
But some say it has resulted in way too much testing and
way too many biopsies. Dr. H. Gilbert Welch, a professor of
medicine at Darmouth College and at the Department of
Veterans Affairs Medical Center in White River Junction,
Vt., attributes the appeal of the number four to "digit
preference." Doctors, he said, like whole numbers, they
like clear results.
Unfortunately, he said, cancer, and prostate cancer in
particular, is not like that. "If the P.S.A. gets very
high, it is telling us something," he said. But lower
levels, certainly levels below 10, lead to the discovery of
microscopic cancers that no one understands. Most are
harmless and will never grow. Some are dangerous, but there
is no way of distinguishing between the two. "We just don't
know what it means," Dr. Welch said.
Prostate cancer is so common that virtually every man gets
it if he lives long enough, said Dr. Thomas A. Stamey, a
professor of urology at Stanford. Yet only rarely is it
life-threatening. Screening, Dr. Stamey said, fueled by a
false sense of confidence in what is normal and what is
not, has led to far too many biopsies, far too many
discoveries of cancers that pose no danger, far too many
prostates removed or destroyed.
Dr. Catalona is of the opposite camp. He says he has moved
his cutoff down a notch, to 2.5. He has seen too many men,
he says, who ended up with deadly cancers because they
waited for their P.S.A. levels to creep above four before
having a biopsy.
But Dr. Stamey said, "I have some smart colleagues who are
very proud of the fact that they used to stand up at
meetings and say, 'I never had a P.S.A. test in my life,
and I don't plan to have one.' " Given the new study, he
said, "it looks like they were very insightful."