Questions Outnumber Answers on P.S.A. Test

By JANE E. BRODY

NY Times, February 18, 2003

Many women have hesitated to get mammograms because they know the unpleasant realities they face if anything suspicious appears, especially since there are no guarantees that treatments will be lifesaving or even necessary.

Now men middle-aged and older face a similar dilemma with the P.S.A. blood test for prostate cancer, but with far greater uncertainty as to benefits versus risks.

The Controversy

Many men who otherwise are careful about their health and have regular checkups are now hesitating to avail themselves of the P.S.A. test. Although the American Cancer Society, among others, recommends an annual P.S.A. for all men over 50 and even earlier for men with a family history of prostate cancer, some physicians and medical experts have advised against it.

Citing inadequate data, the U.S. Preventive Services Task Force has no recommendation, either for or against the testing.

When the blood level of P.S.A., or prostate specific antigen, rises above four nanograms per milliliter, doctors usually urge a biopsy. Cancer will be found in about half of those patients, but it may never become symptomatic or life threatening.

Furthermore, the P.S.A. can rise for other reasons, like benign prostate enlargement, which occurs in all men as they age.

Cost of the blood test, which is minimal, is not an issue. But if the P.S.A. test is positive, it typically leads to a $1,500 biopsy, with ultrasound guidance and samples taken from various parts of the prostate, to find out if cancer is present.

And while a mammogram can pinpoint a suspicious area of the breast, the P.S.A. cannot. And a prostate biopsy can miss a cancer.

If cancer is found, there is no certain way to know how deadly it is, or if it will ever be deadly, although scientists are now searching for markers to indicate how aggressive a prostate cancer may be.

In autopsies of men over 50, as many as half have been found to have cancer cells in the prostate that have neither spread nor caused symptoms and in many cases would probably never have been fatal. In autopsies of men over 80, 70 percent show signs of the cancer.

Yet, once cancer is detected, how many men can live comfortably without having it treated? After all, except for lung cancer, prostate cancer kills more men, about 30,000 last year, than any other cancer.

Difficult Decisions

Deciding to be treated and choosing a treatment can be anxiety-provoking. Rudolph W. Giuliani, the former mayor of New York, spent months weighing the options before choosing implanted radioactive seeds, followed by external radiation.

Last week, Senator John F. Kerry, a Democratic presidential candidate from Massachusetts, had his cancerous prostate removed. In opting for surgery, he selected the treatment with the best record for long-term survival.

Still, any treatment can have lasting side effects, including impotence and incontinence, that may seriously compromise a man's quality of life.

Although modern nerve-sparing surgery can minimize the risk of these complications, many surgeons are not trained in the best techniques and, even when they are, the risk of impotence remains high.

Even with expert surgery, one study showed, 9 percent of men had problems with urinary control a year after treatment, and 58 percent had problems with sexual functioning.

Those undergoing other forms of treatment, namely radiation, did not fare much better.

In an article published in December in The American Journal of Medicine, researchers from the University of North Carolina and the University of Massachusetts in Boston noted that screening men for prostate cancer had become popular even though it had not been shown to be lifesaving in a randomized clinical trial.

There is "a disconnection," these researchers maintain, "between the degree of enthusiasm for screening and the quality of the evidence supporting it."

On the other hand, cancer experts in favor of screening point out that prostate cancer death rates among American men have dropped decisively in the last decade, following the introduction of the P.S.A. test. The National Cancer Institute last year documented a "dramatic decline" in the prostate cancer death rate per 100,000 men ages 50 and older since 1992; before 1992, the rate had been rising steadily.

In a second study, in Austria, the death rate from prostate cancer dropped 42 percent below expected levels within five years in Tirol, the only state that offers the P.S.A. test at no charge. Two-thirds of men ages 45 to 75 were tested.

Yet, some argue that it is not possible to know whether this improvement is a result of P.S.A. screening or faster and better treatment, or both.

A major study, the Prostate Cancer Prevention Trial, is now under way at 222 sites. It should eventually reveal the true value of screening, using both the P.S.A. and digital rectal exam, for three consecutive years. The men, ages 55 to 74, will be followed for 10 years.

In an editorial accompanying the journal article, Dr. Timothy J. Wilt and Dr. Melissa R. Partin of the Minneapolis Veterans Affairs Center for Chronic Disease Outcomes Research urge men to be more fully informed about possible consequences and uncertainties before they have the P.S.A. screening.

Now, they note, "the perceived seriousness of prostate cancer, the innocuousness of the P.S.A. test and the risks associated with screening when there is a diagnosis of cancer discourage careful deliberation of the screening decision."

The Minneapolis researchers say that "providers and health plans should neither actively promote nor deliberately dissuade patients from being screened, but rather adequately inform and involve them in screening decisions."

Since a full discussion of benefits and risks is unlikely during the brief medical visits now permitted under managed care, every man should become well-informed on his own about the risks and benefits of screening and early treatment for prostate cancer. But since even experts have difficulty arriving at reasoned decisions, the task will not be easy for laymen.

Improving the P.S.A.?

Experts generally agree that the P.S.A. is not an ideal marker for prostate cancer. In hopes of improving its predictive value, some doctors suggest that when the reading is minimally elevated, sequential tests be done a year or more apart, with a biopsy performed only when the P.S.A. rises by 25 percent or more.

Others have tried recalculating the P.S.A. level, taking the volume of the prostate gland into account. Still another approach adjusts the P.S.A. finding to the man's age, with suspicion of cancer raised when a man under 50 has a P.S.A. above 2.5 nanograms , while 6.5 might be considered as normal for a man in his 70's.

The most promising approach so far involves calculating the ratio of freely circulating P.S.A. to the total P.S.A. level. In a study of 773 men, half of them found to have cancer, those with higher total P.S.A.'s were more likely to have cancer; those with more freely circulating P.S.A. were more likely not to have cancer.

Whatever method is used to improve the reliability of the test, it must retain its ability to detect nearly all cancers. At the same time, it should improve its results in distinguishing between prostate cancers that are potentially lethal and those that will never cause trouble.