SCREENING AND DIAGNOSIS
Spotting Prostate Cancer Sooner
Until we are able to prevent
prostate cancer, our goal is the next best thing -detecting the
disease at its earliest, at a point where the tumor is curable in
men who are going to live long enough to need to be cured. Already,
thousands of lives have been saved by the highly effective "one-two
punch" of the PSA blood test and the digital rectal exam. Over
the last decade, Brady investigators have major improvements in
the use of PSA as a meaningful and specific screening tool; of particular
importance has been our scientists' work in PSA velocity - its rate
of change from year to year. In this work, we have been fortunate
to have access to a massive database called the Baltimore Longitudinal
Study of Aging. (Since it was begun in 1958, about 1,500 men have
participated in this BLSA study, returning every other year for
physical examinations and a battery of medical tests. Their blood
samples from every checkup are stored for future studies.) In a
series of landmark investigations, looking at 20 years' worth of
stored blood samples, we found that up to 10 years before diagnosis
the men who developed prostate cancer showed significantly greater
rates of change in PSA levels than the men who remained cancer-free.
By tracking these changes, we were able to detect prostate cancer
long before it could be diagnosed by other means. Still, although
impressive, PSA velocity is not a foolproof system; for several
reasons, including the way some tumors make PSA, it does not detect
every cancer early.
"Smarter" diagnosis
Of course, diagnosing cancer
in time to treat it effectively is crucial. But the issue is complicated
by the fact that all prostate cancer are not created equal. Some
are very slow-growing, and never need treatment; others can be fatal
within a matter of months after they are diagnosed. So for us, just
as important as finding cancer early, is knowing which kind of cancer
- the "good" or the "bad" -- we're dealing with.
Research at the Brady Urological Institute has established the guidelines
on which men can afford to "watch and wait." We are also
working to pinpoint the men at the other end of the spectrum - those
with aggressive cancers that will almost certainly be lethal if
not treated immediately.
Once again, the BLSA has
proved an invaluable resource. In one study, comparing blood samples
of men who developed prostate cancer 15 years before diagnosis with
those who did not, we have established the safe rate at which PSA
can change every year in men, and have determined that - many years
before a tumor may be otherwise detectable - "free" PSA
may be an excellent predictor of aggressive cancers that will need
to be treated. (In the bloodstream, some PSA molecules are glued,
or "bound" to certain inhibitors that prevent the PSA
from breaking down protein; other molecules, however, are unfettered
- they're "free"). Brady scientists are working to characterize
these forms of PSA in the bloodstream, measure each part, and determine
what these levels mean over time. We have recently incorporated
MRI evaluations of the prostate into these BLSA evaluations; in
the long run this, too, should give us yet another important tool
for charting the course of normal and abnormal growth of the prostate.
Cracking the code of Hereditary Prostate Cancer
In 1992, William Isaacs
and other researchers at the Brady Urological Institute were the
first to establish an undeniable link between a family history of
prostate cancer and a man's risk of developing the disease, and
to characterize the distinct phenomenon of Hereditary Prostate Cancer
(HPC). We proved that prostate cancer, like other cancers, can be
inherited - a fact once widely doubted. Most recently, we identified
the general location of the first susceptibility gene (there are
almost certainly others) for prostate cancer, called HPC-1. An estimated
250,000 American men may carry this defective gene; in these men,
the odds of developing prostate cancer are extremely high. Once
we have successfully cloned this gene, we will have a powerful tool
to spot cancer early in men who have inherited this potentially
lethal mutation. Also, discovering how this mutated gene triggers
the cascade of prostate cancer may help us find new ways of preventing
or treating the disease in all men. Although only about 10 percent
of all cases of prostate cancer are thought to be purely hereditary,
we believe that the defective gene or mechanisms involved in HPC
are the same ones that somehow go askew in "sporadic"
cancer (disease that just develops over the course of a lifetime
- the kind most men get.) Here, as well, we have a one-of-a-kind
resource - our pool of 2,500 families with HPC whose DNA may help
us crack the genetic code of prostate cancer. If you want to participate
in this study please click here for
details
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