Posted on 05/26/2004 7:22:39 PM PDT by neverdem
Significant numbers of older men whose results on a popular screening test for prostate cancer are normal may nonetheless have cancer, a new study has found.
The result, medical experts say, raises questions about what a normal test score should be and whether these men are better off let alone or treated when, through biopsies, cancer cells are discovered.
It also amplifies a controversy over the test, known as the P.S.A., and whether finding prostate cancer early and treating it by removing or destroying the prostate is, on balance, helping or harming men.
The P.S.A. test is a blood test that looks for prostate specific antigen, a protein released by prostate cells. When the prostate gland enlarges, whether because of cancer or benign conditions, P.S.A. levels in the blood tend to rise.
The test was initially used to look for recurrences of cancer after men had been treated. But in the 1990's it came into widespread use as a screening test to find new cancers.
In that context, cancer experts informally agreed upon a convention: When a P.S.A. test finds more than four nanograms of the protein in a milliliter of blood, doctors usually recommend biopsies to see if cancer is present; needles are inserted into the prostate to withdraw cells for analysis. When a biopsy finds cancer, almost all men opt for treatment, usually surgery or radiation to destroy the prostate gland.
But the new study, being published today in The New England Journal of Medicine, reports that as many as 15 percent of men with P.S.A. levels less than 4 had cancer when their prostates were assessed with biopsies.
While higher P.S.A. levels confer greater risk, there appears to be no level at which there is no risk of prostate cancer, said the lead investigator, Dr. Ian M. Thompson, chief of urology at the University of Texas Health Science Center in San Antonio.
Dr. Howard Parnes, who directs prostate cancer research at the National Cancer Institute's division of cancer prevention, responded to the study by saying: "Now we don't have a clear definition of normal and abnormal. Before these data were out, we were comfortable with the notion that 4 is a cutoff between normal and abnormal. Now these data very clearly tell us that 4 is not a cutoff."
But the study, which involved 2,940 men aged 62 to 91, was not designed to show what cutoff should be used for P.S.A. levels. And there are no easy answers about whether a man with a low P.S.A. level should have a biopsy, said Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society. Cancers in such men are microscopic — a doctor cannot feel them — and there are no symptoms. The biopsy decision may depend on how old the man is, or his family history, or how frightened he is of prostate cancer.
"These are decisions that are going to have to be discussed between people and their health care providers," Dr. Lichtenfeld said.
Dr. Parnes worries that men with low P.S.A. levels and their doctors will see the study results and decide unequivocally that the safest thing to do is have a biopsy. In that case, since about 90 percent of men have levels that are below 4, huge numbers would have biopsies, huge numbers would be told they have cancer, and huge numbers might opt for treatment that is perhaps unnecessary.
Prostate cancer is exceedingly common; autopsy studies in which prostates are examined section by section find microscopic cancerous cells in most elderly men. But it tends to smolder silently, never spreading or causing problems in a man's lifetime.
Still, it can be deadly. Prostate cancer kills 30,000 American men a year. As yet, there is no way to know for sure whether a cancer will spread and kill, so most men choose treatment although it can lead to impotence or incontinence.
The uncertainties mushroom as earlier and earlier cancers are found.
To gauge risk, pathologists grade cancerous cells, assessing how disordered and abnormal they look. In the new study, among the men with P.S.A. levels less than 4 whose biopsies showed cancer, 14.9 percent had high-grade cancers, in which the cells look aggressive and threatening under the microscope. But even that result is difficult to interpret, Dr. Parnes said, because the association between grade and outcome is based on studies of much larger cancers, in men with much higher P.S.A. levels.
"Most people would assume that the high-grade cancer cells are going to be significant if you live long enough," Dr. Parnes said. "But because we are diagnosing the cancers so early, we don't know how long they would take to manifest. And not everyone is going to live long enough to develop clinically relevant cancer. The lower the P.S.A. threshold, the deeper into the unknown you're going."
Some, like Dr. H. Ballentine Carter, a professor of urology and oncology at Johns Hopkins University, urge caution about biopsying men with P.S.A. levels below 4.
"We will find a lot of cancer, and we will not know what to do about it," Dr. Carter said. "That is very worrisome."
"The reason for caution," Dr. Carter said, "is because right now we don't have the ability to know who in this low P.S.A. range has a cancer that is likely to be harmful. There is nothing wrong with doing a P.S.A., but we don't need to act on it immediately. We have an out here: We can follow men over time, and biopsy those whose P.S.A. goes up."
Dr. Thompson, the study's chief investigator, said men needed to be counseled about their options. "People say, `What's the problem with treating it?' " he said. "But every treatment has side effects."
"Even watchful waiting comes with a cost," he added, explaining that the option of being monitored to see if a cancer grows or a P.S.A. level rises can exert a psychological toll.
For now, said Dr. Lichtenfeld, of the American Cancer Society, the question will be whether the old P.S.A. cutoff point of 4 should be moved down.
"There's obviously intense discussion," he said. "We may move it down, but we have to weigh the risks and benefits. We will find more prostate cancer, and we will find more cancers that didn't need to be found. We will cause some men harm that they didn't need to have."
Dr. H. Gilbert Welch, a professor of medicine for the Department of Veterans Affairs and at Dartmouth, said the new study should make men reconsider whether they want a P.S.A. test at all.
"The study begins to highlight that we really don't know what we're looking at," Dr. Welch said. "There's a disconnect between the word `cancer' as most of the public understands it — a very aggressive disease that leads to death if not treated — and the way the pathologist understands it, as a few cells that may not be relevant."
It is becoming increasingly clear, Dr. Welch said, that the more pathologists look for cancer, the more they find it, but that this does not mean the cancer is worth finding.
"At some point this has got to be crazy," he said. "Everyone can't have prostate cancer."
"Is our goal to get rid of all prostate cancer, or is it to maximize the public health?" Dr. Welch said. "This really says we need to figure out better ways to find out who really does have the cancer we care about."
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