As reported by The Hartford Courant, June 29, 2004.

Muddying the PSA Waters

By Garret Condon

Some numbers shed light on prostate cancer. For example, one in six American men will be diagnosed during his lifetime. One in 32 - nearly 30,000 individuals - will die of the illness this year. It is the second most common cancer in American men, after skin cancer.

But one number can be as confusing as it is enlightening. That is the result of the prostate-specific antigen test, a key screening test for cancer of the prostate - the walnut-size male sex gland that secretes some of the fluid that carries sperm in ejaculation.

The PSA test measures the blood level of prostate-specific antigen, a protein made by all healthy prostates. This level increases with the presence of prostate cancer - as well as with infection or an enlarged prostate. Most men have less than 4 nanograms of PSA per milliliter of blood. Above 4, the chance of having prostate cancer increases by 25 percent. Above 10, the risk rises to 67 percent, according to the American Cancer Society.

The New England Journal of Medicine recently published a study showing that 15 percent of participants with PSA test results in the normal range had cancer, and 15 percent of those had aggressive cancers. This was not a shock to the urologists and cancer specialists who treat prostate cancer. They say the PSA test is a single tool and that results must be interpreted differently for different patients. But some worry that while the PSA test can help pick up cancer, it can't help doctors distinguish between deadly tumors and those that, left alone, would have little impact on a patient's life.

"I would say that the ambiguity and uncertainty around PSA-based screening programs is becoming murkier and murkier," said Dr. Marc Garnick, professor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston. Garnick, an expert in urologic cancer who also is chief medical officer at Praecis Pharmaceuticals in Waltham, Mass., said he and many in his field believe that early PSA screening may be saving and extending lives, but it will be years before large studies in the United States and Europe demonstrate this beyond doubt.

The PSA test may not be a perfect test, but it's still a very useful one, said Dr. Vincent Laudone, an attending urologic surgeon at Hartford Hospital. He said he thinks it's important that men understand that the PSA test - bad press or not - is still valuable.

The recent study, he said, "reinforced the need to look at PSA as not just normal or abnormal." The PSA number tends to go up in most men as they get older, so the age of a patient is a key to making sense of the results. Although a result lower than 4 is normal overall, he said, a 40-year-old with a 2.5 would be considered too high and a 75-year-old might be normal with a 5.5.

Dr. Thomas Trono, chairman of the department of urology at St. Francis Hospital and Medical Center, said he doesn't use a number when he talks to patients about PSA tests. "What I tell my patients is that you need further investigation if a digital rectal exam shows a lump and/or your PSA is higher than we think it should be," he said. Of immediate concern is a quick upturn in PSA test results over time.

That's what got Trono's attention with Alexis Lopez, a middle-age Glastonbury man whose PSA numbers started going up, although they were below 4. Lopez agreed that a biopsy was needed. The biopsy showed cancer, and Lopez opted for surgery to remove the gland. He said he was glad to catch it early because he had seen his father put off treatment for testicular cancer that later spread to his bones.

"So far, everything is good," said Lopez, who is now 47.

Any such upward trend in the PSA level - and even a single test result deemed high for a patient's age - should prompt a doctor-patient talk about the pros and cons of biopsy and treatment, said Dr. Joseph Cardinale, director of the Father Michael J. McGivney Cancer Center at the Hospital of St. Raphael in New Haven.

That discussion is central to the screening process because some medical organizations don't recommend annual PSA tests. Even organizations that do, such as the American Cancer Society and the American Urological Association, make a point of soft-pedaling the advice. They suggest that health-care professionals "offer" an annual PSA and digital rectal exam to men 50 and older and high-risk men beginning at 40.

Organizations that don't advocate routine testing for prostate cancer - including the U.S. Preventative Services Task Force, the American College of Physicians and the National Cancer Institute - speak instead about getting patients to understand the risk factors for prostate cancer as well as the advantages and disadvantages of further diagnosis and treatment.

The risk of prostate cancer increases with age. However, early cancer caught late in life might be left alone because the patient may not be able to withstand treatment, and other health problems could lead to death more quickly. Patients with a family history of prostate cancer - in a father or brother - are at higher risk, as are African Americans. (Native Americans have the lowest risk of the disease.) Obesity, possibly linked to high-fat diets, is being studied as another potential risk factor.

Dr. Peter Albertsen, professor and chief of urology at the University of Connecticut Health Center, said some men may have other health problems - heart or lung disease, for example - that are more pressing. In such a case, prostate cancer is unlikely to cause the patient any harm, and treatment might be put off indefinitely.

Albertsen said that any man who gets a PSA test result that is even close to abnormal should repeat the test. If the result is in the low range, from 2.5 to 4.0 in a patient 45 to 60, the man might wait a while and repeat the test to see if there is an upward trend.

"Just don't be in a hurry to go off and get your biopsy," he said. And if a physician recommends aggressive therapy, such as surgery or radiation, he said, the patient should get a second opinion.