As reported by The New York Times, June 20, 2005.

P.S.A. Test No Longer Gives Clear Answers

By Gina Kolata

Last November, Rabbi Samuel M. Stahl was worried that he might have prostate cancer. He had had two P.S.A. tests in the past six months. Both times, his levels were well within the range that had been considered normal, but the second level was higher than the first.

His internist told him to relax. The blood test looks for a protein, the prostate specific antigen, which can signal cancer. Only test results higher than 4 were worth worrying about, the doctor contended, and both tests were below that.

But Rabbi Stahl, who lives in San Antonio, remembered advice he had gotten from a stranger three years ago that suddenly felt eerily prescient.

The rabbi was walking out of the city's Ecumenical Center for Religion and Health when he passed a man who was walking in.

"The man said, 'Are you here for the prostate cancer support group?' " Rabbi Stahl recalled. "I said no. Then he said: 'I just want to give you a bit of advice. Don't pay attention to the absolute P.S.A. number, but if you see it rising, that's a cause for concern.' "

Rabbi Stahl's first P.S.A. was 2.4. But the second one was 3.4. He had to find out: was that jump ominous or inconsequential?

Rabbi Stahl had stumbled into one of the great issues in medicine today. No longer is the P.S.A. test a simple screen with a sharp cutoff at 4. Now, prostate cancer experts say, all bets are off.

The P.S.A. test "is just not as discriminating as we thought it was," said Dr. Michael J. Barry, a professor of medicine at Harvard Medical School.

As a result, many experts are suggesting that the P.S.A. not be the single focus of prostate cancer screening, but rather one piece in a puzzle with other risk factors. Some experts are also asking doctors to be more open to the idea that some men may be better off forgoing treatment and instead be monitored regularly for changes in their tumor's growth. The muddied story emerged in a sequence of medical papers over the last year.

First Dr. Ian M. Thompson Jr., chief of urology at the University of Texas Health Science Center at San Antonio, published a paper in The New England Journal of Medicine reporting that biopsies found prostate cancer in as many as 15 percent of men with P.S.A. levels below 4.

Then Dr. Thomas Stamey, professor of urology at Stanford University School of Medicine, published a paper in The Journal of Urology saying that P.S.A. tests were virtually useless. In most men, P.S.A. levels of 2 to 10 are caused by nothing more than a harmless enlargement of the prostate that occurs when men age. But prostate cancer is so common that biopsies find prostate cancer in most middle-aged and older men if doctors look hard enough. So the results would be the same if doctors simply biopsied men age 50 and older than if they did a P.S.A. test first.

And last month, Dr. Peter C. Albertsen of the University of Connecticut Health Center published a study in The Journal of the American Medical Association saying men with prostate cancers that do not look particularly aggressive under a microscope - the majority of men whose cancers are found with P.S.A. tests these days - can do perfectly well with no treatment for at least 20 years. All they need is to be monitored by a doctor to ensure that their P.S.A. levels are not shooting up.

On the other hand, a Swedish study published last month in The New England Journal of Medicine lumping men with more as well as less aggressive cancers found that those who had their prostates removed had a lower risk of death and of metastatic cancers than those who did nothing. But these men generally started out with larger tumors than the ones that are now being found with P.S.A.'s.

So what is a man to do?

The problem, said Dr. Timothy Wilt, a professor of medicine at the Minneapolis V.A. Medical Center, is that most men eventually develop prostate cancer, but most of the time it grows so slowly that it never causes problems and eventually they die of something else, never knowing they had cancer. Unless, of course, a doctor starts biopsying their prostate. With annual P.S.A. tests, sooner or later many men will end up with a biopsy.

"And as we repeatedly biopsy men, we are likely to find these subclinical prostate cancers," Dr. Wilt said. "There is no doubt that we will label more people as abnormal," telling them they have cancer and throwing them into a terrifying whirl of decision making. Despite the arguments in the academic medical community about what the test means, most men are still having it done. But now they have to address these questions: When should a low P.S.A. level lead to a biopsy, and when should a tiny tumor be treated?

There is no easy answer, Dr. Thompson said. In deciding whether to do a biopsy, doctors must weigh other factors along with the P.S.A. Did the patient's father die of prostate cancer? Is he fat? (Fat men tend to have lower P.S.A. levels than thinner men, so a low level in a fat man might be more ominous.) Is he African-American? (Blacks tend to develop more aggressive prostate cancers and at younger ages.) Are his P.S.A. levels steadily rising with no apparent cause, like an enlarged prostate or an infection, both of which cause elevations in the P.S.A.? Or does he have an enlarged prostate, no family history and a previous biopsy that found no cancer?

"You can't condense it to a sound bite," Dr. Thompson said.

But many doctors, he added, are either unaware of the new views on P.S.A. or are ignoring them.

"I was presenting some of the data recently to a gentleman over 50 who was visiting our institution," Dr. Thompson said. "He looked at me with kind of wide eyes and said, 'Do people know this?' " The answer, Dr. Thompson said, is that it appears that most general practitioners do not know it. "They don't know that there is no such thing as a normal P.S.A. level."

Dr. Wilt has another concern. Most patients, he said, are not being counseled that even if they have prostate cancer, they may not need treatment. Only a small percentage of prostate cancers are dangerous, and older men, in particular, with small tumors may be better off monitored instead of treated. Dr. Wilt is directing a study that should help settle the question of whether treatment with surgery helps save lives in men whose prostate cancer is detected by P.S.A. screening, but its results will not be in until 2010.

Often the decision about what to do is thrust upon men who underwent a P.S.A. test without knowing it; their doctor just ordered it as part of a routine physical exam. Then the results came in and the doctor said the dreaded word, cancer.

That is what happened to Michael Karp, a 78-year-old retired pharmacist who lives in Faribault, Minn.

Back in November 1994, he said, his doctor told him he had had a P.S.A. test and his level was high. He was astonished. He had no idea he'd been tested. "I didn't even know what a P.S.A. was," Mr. Karp said.

A biopsy was done, but no cancer was found. His P.S.A., 7.2, was presumably from a urinary tract infection.

But, Mr. Karp said, his doctor insisted on yearly tests, and Mr. Karp, having experienced a cancer scare, did not dare refuse. The doctors, with their talk about P.S.A.'s and cancer, had made an indelible impression. "They've got you worried, they're in your head," he said.

Then, a few years ago, his P.S.A. rose to 11.4 and a biopsy uncovered cancer.

"I was all shook," Mr. Karp said. Should he have his prostate removed or destroyed, risking impotence or incontinence?

"I went to Dr. Wilt," he said, who gave him another option.

"He says to me: 'If you were in Sweden, you know what would happen? Nothing,' " Mr. Karp said. "It kind of woke me up." His P.S.A. level has continued to rise, but he is happy with his decision to have regular monitoring and no treatment. "I'm doing fine," he said.

As for Rabbi Stahl, at age 65, he had hoped for many more healthy years ahead and did not want to ignore his rising P.S.A. At his insistence, his internist reluctantly referred him to a urologist who did a biopsy, finding a small cancer but one with cells showing the kind of deranged structure associated with an aggressive cancer.

On Feb. 28, the rabbi had his prostate removed.

He said his internist defended his decision to ignore those low P.S.A. levels, telling him he had no regrets. "He said he'd do it again the same way," Rabbi Stahl said. So he changed doctors.

And, he said, he will always be grateful to the stranger who gave him the unsolicited advice. "If I had not run into that man, I would have done nothing," Rabbi Stahl said. "It was a message from God."