Watchfully Waiting
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Problems With PSA Testing

Two new studies in the New England Journal of Medicine question the benefit of a common cancer screening test.

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By Damaris Christensen

Watchfully Waiting

Doctors and patients are looking for better ways to identify prostate cancer

By Damaris Christensen


Over the last few years, researchers have focused increased energy on finding ways to improve or replace PSA testing, the most common prostate cancer screening tool, by searching for new markers of the disease in a man’s blood or urine. The PSA test measures the blood concentration of prostate-specific antigen (PSA), a protein made by the prostate gland. Doctors adopted the test quickly after PSA was linked to prostate cancer in 1987; many researchers and patients believe it has helped identify cancers early and reduce deaths.

Even so, PSA testing “is widely recognized as imperfect,” says Howard Parnes, a medical oncologist in the division of cancer prevention at the National Cancer Institute (NCI). Since PSA levels rise not only with prostate cancer but also with benign conditions such as an enlarged prostate or prostatitis, many men will have high PSA levels yet not have cancer. And a recent study has suggested that about 15 percent of men who have comparatively low levels of PSA actually have cancer. Those PSA problems provide an impetus for the hunt for new prostate cancer biomarkers.

But identifying reliable new biomarkers could do much more. With more than 80 percent of men with prostate cancer living long enough to die of other causes, “the relevant question today is not detecting prostate cancer, it is detecting the bad actors,” or the dangerous cancers, says Ruth Etzioni, a biostatistician who focuses on prostate cancer studies at the Fred Hutchinson Cancer Research Center in Seattle. In fact, many men with prostate cancer enter so-called watchful waiting, or active surveillance after diagnosis, on guard for signs their cancer is aggressive before getting treatment. Etzioni makes a “bold suggestion” that screening for only aggressive forms of the cancer may be the way to go—if such a test can be developed. “Why do you want to be detected if you aren’t going to be treated?” she asks.

Many researchers agree that the long-term goal is to develop just such a test, to identify the men who have aggressive and potentially deadly prostate cancer. But at least at first, new biomarkers are more likely to supplement existing PSA testing by helping doctors identify which men with high PSA levels need biopsies and which men do not. As the population ages and more men get PSA tests, the number of men who worry that they have prostate cancer when they do not is steadily increasing, and represents an immediate crisis, says Robert Getzenberg of the Brady Urological Institute at Johns Hopkins University in Baltimore. “There are many people out there [with high PSA levels] who have negative biopsies but just aren’t reassured they don’t have ticking time bombs inside,” he says.

Getzenberg and his colleagues recently reported on a potential new biomarker for prostate cancer. The research team examined the blood of 385 men to measure the concentration of a protein called EPCA-2, which is made in prostate cancer cells. They found that blood levels of this protein correctly identified 97 percent of men who did not have prostate cancer and 94 percent of those with prostate cancer, regardless of PSA levels. In fact, the test could distinguish between men with localized prostate cancer and those with cancer that had spread outside the organ, they reported in the April 2007 Urology.



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