Prostate Cancer: Two Steps Forward

New tests may cut down on unnecessary biopsies

Prostate cancer has certainly gained a higher profile in recent years. The second leading cause of cancer death in men after lung cancer has its own U.S. postage stamp and its own celebrity patients, media tycoon Rupert Murdoch and Yankees manager Joe Torre among them. The American Cancer Society estimates that 318,000 new cases will be diagnosed in the U.S. this year, and some 40,000 will die from the disease. That is particularly disheartening, because prostate cancer is almost 100% curable when caught early.

It seems surprising, then, that doctors can't reach a consensus on so basic a question as whether routine screening is necessary. That's because the current method of prostate cancer detection, the protein-specific antigen (PSA) test, is notoriously inaccurate. More often than not, it mistakes a harmlessly enlarged prostate for cancer, resulting in tens of thousands of unnecessary biopsies each year, at an average cost of $1,300 each. Although the ACS advocates the test for men 50 and over, some researchers estimate that unnecessary biopsies would cost the U.S. as much as $12 billion a year if those guidelines were followed.

That could change in May, when the ACS is set to evaluate a much improved method for prostate cancer--Beckman Coulter Inc.'s free-PSA test, available since March, 1998. Meanwhile, an even more precise DNA test is under development and could eventually take some heat out of the debate.

KNOTTY PROBLEM. At issue is a knotty medical conundrum: Could widespread diagnosis be worse than the disease? Because the cancer grows so slowly--especially in older men--many men can live a full life with a small tumor. Removing the tumor, on the other hand, can cause incontinence, impotence, and increased susceptibility to secondary tumors. "No question that in some patients the treatment is worse than the disease," says Dr. Howard I. Scher, chief of the genitourinary oncology service at Memorial Sloan-Kettering Cancer Center in New York.

Many prostate tumors, of course, are horribly lethal, and no one can predict which is which. Since the PSA test was introduced in the early 1990s, the death rate from prostate cancer has dropped by 2% a year, while the incidence has increased. But critics are reluctant to attribute the drop to wider screening. In a series of reports published last year in the Journal of the National Cancer Institute, researchers concluded that PSA testing likely played only a partial role in the declining mortality. "We still need better tests--that is definite," says Dr. Alan W. Partin, professor of medicine at the Johns Hopkins University School of Medicine. "We still are performing far too many unnecessary biopsies, even with free-PSA."

No one is sure what causes prostate cancer. It is considered a silent disease--producing symptoms such as difficulty urinating, blood in the urine, and impotence only when the tumor has spread to the point where it is often incurable. The prostate itself is a walnut-shaped gland around the urethra that is responsible for about 30% of the volume of semen during ejaculation. As a man ages, his prostate grows, and just about every man, if he lives long enough, will develop a condition called benign prostatic hyperplasia (BPH)--i.e., an enlarged prostate. BPH afflicts an estimated 14 million American men, including more than 50% of men over 60. Although it can be painful, it is usually left untreated.

Unfortunately, an enlarged prostate also causes PSA levels to rise, leading to all the false positives on the standard PSA test. Even when coupled with a quick rectal exam to detect any abnormalities, as many as 80% of PSA tests turn out false positive readings. "I have had patients undergo up to 14 unnecessary biopsies because they had high PSA ratings," says Dr. Peter H. Gann, a medical professor at Northwestern University Medical School in Chicago. More frightening, the test turns in false negatives 20% of the time, missing the cancer completely.

IN THE PIPELINE. While the PSA test measures all the enzyme swirling through the bloodstream, the new test measures only those molecules--called free PSA--that do not bind to proteins in the blood. Free PSA is known to be lower in men with prostate cancer than those without cancer or with BPH.

The new test got a boost from a study reported at the American Association for Cancer Research (AACR) annual meeting in April. Researchers led by Gann tested the blood of 430 men later diagnosed with prostate cancer and 1,642 controls who did not develop the disease over 12 years. The free-PSA test reduced false positive readings by up to 42% and found 10% more cancers than the PSA test alone.

Even more accurate tests are in the labs, including the first to measure DNA for genetic alterations related to prostate cancer. This test, developed by Paul Cairns of Fox Chase Cancer Center in Philadelphia and others, analyzes urine for an early genetic modification called methylation, unique to cancer cells. Cairn's team reported at the AACR meeting that 22 of 28 prostate tumors showed methylation--and the same mutation was found in six of the corresponding urine samples. "It is likely that there are cancer cells in body fluids years before cancer is clinically detectable," says Cairns. "If we can find those cells, we can cure more prostate cancers." One goal, surely, that the medical community would agree on.

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