Mohamad E. Allaf, M.D.
Trinity J. Bivalacqua, M.D, Ph.D
Arthur L. Burnett, II, M. D.
H. Ballentine Carter, M.D.
Misop Han, M.D.
Jacek L. Mostwin, M.D., D.Phil,(Oxon.)
Alan Partin, M.D., Ph.D
Christian Pavlovich, M.D.
Edward M. Schaeffer, M.D.,Ph.D.
Mark P. Schoenberg, M.D.
Patrick C. Walsh, M.D.
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.
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