November 25, 2015

   A Publication of the James Buchanan Brady
   Urological Institute Johns Hopkins Medical Institutions

Volume III, Winter 2007

Breakthrough: New Prostate Cancer Test is More Specific than PSA

Getzenberg, left, and Partin. The EPCA-2 test can even tell organ-confined cancer from cancer that has spread beyond the prostate.

As good as PSA is in detecting prostate cancer, there's a lot of room for improvement. "Nobody would call PSA a perfect test," says Robert H. Getzenberg, Ph.D., the Brady's Research Director, and the Donald S. Coffey Professor of Urology. For one thing, "PSA is not specific for prostate cancer. It is often elevated in men with BPH and prostatitis," inflammation of the prostate. Another flaw: "It tells us that a man has cancer, but it doesn't tell us much about what kind of cancer we're dealing with," notes Alan W. Partin, M.D., Ph.D., Director of Urology. "Is it aggressive? Is it a milder, slower-growing cancer? These are very important things a man with prostate cancer would really like to know."

Millions of American men — more than 25 million, says Getzenberg — are waiting from biopsy to biopsy, playing a frustrating form of medical roulette, just looking for an answer: Their PSA test is higher than it should be, but despite many needle sticks, no cancer has been found on biopsy. So why isn't the PSA level lower? The idea of cancer growing, but being repeatedly missed, can be very troubling for these men. For years, Hopkins researchers have been working to find a better, more specific "crystal ball" for prostate cancer. Now a research team, led by Getzenberg, has found one, called EPCA-2 (early prostate cancer antigen-2), that works in a simple blood test.

The EPCA-2 test involved years of work and many dedicated scientists, including (Back row): Grant
Cannon, Timothy McMurray, David (Brandy) Yeater. (Middle row) Katherine Bright, Robert Getzenberg,
Eddy Leman, Elizabeth Dada, Megan Gurganus. (Front row) Simran Jandu, Donald Vindivich.

Their discovery comes after decades of work by Getzenberg's predecessor, Donald S. Coffey, Ph.D., who noticed something striking about the nuclei of cancer cells: They're funny-looking; they're misshapen. Coffey and Getzenberg then characterized the structural proteins that caused this mess within cancer cells; they're in a part of the nucleus called the nuclear matrix. One of these is EPCA-2. In a series of exciting experiments, using a technique called "focused proteomics," Getzenberg and colleagues were able to show that EPCA-2 was far more specific than any other marker identified so far — even PSA — in distinguishing men with prostate cancer from other men. Further, this test was able to tell which men had organ-confined cancer, and which men had cancer that had spread beyond the prostate.

“Our goal has been to try to identify at the molecular level what the pathologist sees under the microscope," Getzenberg explains, and so far, EPCA-2 has performed like a champ. In tests of more than 600 men, "even in men where PSA has failed, EPCA-2 is almost one hundred percent specific for prostate cancer, and picks up greater than 90 percent of the prostate cancer patients." More good news: EPCA-2 does not appear to be elevated in conditions like BPH and prostatitis. And, EPCA-2 can detect the presence of prostate cancer in men with normal PSA levels. EPCA-2 may even be able to distinguish the deadliest cancers, which quickly develop the ability to spread beyond the prostate, from those that are less aggressive. More tests are needed, and EPCA-2 will soon be studied in a large, multicenter trial, with the goal of obtaining FDA approval for its use.

Many Hopkins scientists were involved in this groundbreaking work, including Partin; Lori Sokoll and Daniel Chan, two internationally recognized experts in the development of cancer biomarkers; and Bruce Trock, a leading epidemiologist and biostatistician in the field of prostate cancer biomarkers. Much of the work on this project was carried out by a young investigator in Getzenberg’s laboratory, Eddy Leman, Ph.D., working with Grant Cannon.

"These findings are remarkable, and if they hold up when the marker is tested in a larger group of prostate cancer patients, they may revolutionize the approach to screening for prostate cancer," notes Patrick C. Walsh, M.D. At the very least, adds Partin, "EPCA-2 could help determine which men with abnormal PSA levels have prostate cancer. But it's possible that EPCA-2 may even replace PSA one day as the screening test of choice."


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