Many cases of prostate cancer undetected by blood screening

BOSTON -- A disturbing new study has found that 15 percent of older men with supposedly normal readings on the widely used PSA test have prostate cancer anyway -- and some even have aggressive tumors.

The findings intensify the dilemma of how to interpret the test results and how vigorously to treat men with no symptoms.

Some experts think the threshold for what constitutes normal on the PSA test should be lowered, at least in some cases. But others say that could lead to more unnecessary operations in the many men whose tumors are so slow-growing that something else will kill them before the cancer ever does.

"It's a very powerful test, but it's not perfect," said Dr. Leonard Gomella, a urologist at Jefferson Medical College in Philadelphia.

Sixteen percent of American men can expect to be diagnosed with prostate cancer at some point in their lives. Yet most such tumors grow slowly, with the death risk at just 3 percent. Existing screening methods cannot always establish whether cancer is present and dangerous, so some cases are missed and others are overtreated with surgery or radiation.

The study, conducted with the help of funding and personnel from the National Cancer Institute, appears in Thursday's New England Journal of Medicine.

It focuses on the standard screening test for prostate cancer: the prostate-specific antigen test, or PSA count. The blood test has been used on millions of men since the late 1980s to screen those with no symptoms. Many start screening at age 50.

The test measures bloodstream levels of a protein manufactured by the prostate, a male sex gland. Cancer expands the gland, pumping out more of the protein and raising the PSA count. A count of 4 or below (calculated in nanograms per milliliter) has been widely considered to be normal.

However, the researchers found that 15 percent of 2,950 men ages 62 to 91 -- all with normal PSA counts and rectal exams -- had prostate cancer anyway. And 2 percent of the overall group had tumors that looked aggressive under a microscope.

"This study adds to information that perhaps the PSA threshold may be dropped to 2.5 or so," said Gomella, the Philadelphia urologist. "The number 4 may not be the, quote, normal that we look at anymore."

Lead study author Dr. Ian Thompson of the University of Texas at San Antonio said the findings justify stronger measures for some men who have low PSAs but other risk factors, such as prostate cancer in the family.

However, other patients may decide more often to watch and wait, since the findings -- viewed in another light -- add to the evidence that harmless prostate cancer is quite common, Thompson suggested.

"It will allow two men to look at these data and come to different conclusions," he said.

The stakes are high in doing too little. Cancer of the prostate kills more men than any other kind except lung cancer. About 230,900 cases will be diagnosed this year among American men, and around 29,900 will die from it during the same period, according to the American Cancer Society.

There is also evidence that prostate cancer screening is helpful. In the late 1990s, 3 percent more cases were found and 4 percent fewer deaths occurred each year, according to the most recent government data.

However, there is also potential harm in doing too much. An elevated PSA count often stems from slow-growing and ultimately harmless tumors, non-cancerous prostate enlargement, or infection. Prostate cancer surgery leaves many men incontinent or impotent. And biopsies can lead to bleeding or infection in unusual cases.

Also, it has not been conclusively proved that screening explains the falling death rate. Maybe better, not earlier, treatments are saving the lives.

Some doctors fear the study findings will lead to even more unnecessary operations in older patients who are more likely to die of other causes before the cancer kills them.

"I have a sneaking suspicion that what's going to happen is that people are going to start ... being more aggressive with low PSAs," said Dr. Siu-Long Yao, a prostate cancer specialist at the Cancer Institute of New Jersey. "I don't think it's warranted at the present time, but I think people will act on it."

Researchers are studying more subtle ways to interpret PSA counts and experimenting with other protein and genetic tests to help pinpoint the dangerous tumors.

"We desperately need a new marker to tell us who needs to be treated aggressively," said Dr. H. Ballentine Carter, a prostate cancer researcher at Johns Hopkins University.

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On the Net

New England Journal of Medicine: content.nejm.org

National Cancer Institute prostate cancer home page: www.nci.nih.gov/cancerinfo/types/prostate/