Predicting Cancer

By Christine Gorman

Here's a fun quiz for all you armchair oncologists. A 50-year-old man gets a blood test that measures his PSA (prostate-specific antigen)--a substance that is produced only by the prostate. His results edge just past normal, which probably means he has an enlarged prostate. No big deal. Or he could have prostate cancer. "This must be our unlucky day," says his wife, also 50, when he tells her. "I just found out that my mammogram is positive." Which spouse is more likely to have cancer?

If you chose the wife, guess again. In the U.S., about 30% of men who undergo a biopsy after a mildly elevated PSA test have cancer, compared with just 20% of women biopsied after a suspicious mammogram. But there has been so much negative publicity lately about the limitations of PSA tests that most men don't realize how helpful they can be.

Much of the controversy stems from the test's effectiveness in early detection. But its greatest value lies in its ability to help men who already have prostate cancer--a value that was enhanced last week with the publication in the Journal of the American Medical Association of the first detailed study of the natural history of prostate cancer. Researchers from Johns Hopkins used data from the study to develop a formula that gives patients the most precise estimate yet of their chances of surviving a future recurrence.

The most important conclusion to draw from the study is that a rising PSA level after treatment is not necessarily a death warrant. Whenever the prostate is surgically removed (or destroyed by radiation therapy), the PSA level should fall to zero. So unlike the more ambiguous pre-operation tests, any increase in PSA levels after surgery almost always means that some tumor cells have escaped and are growing elsewhere in the body. Prostate cancer usually grows so slowly, however, that patients often die of something else before its spread becomes noticeable.

Not many doctors--or their patients--have so far been willing to take that chance. Most men with an increase in their PSA levels after surgery are given anti-testosterone drugs that target the still invisible metastasis but have significant side effects--effects that amount to a chemical castration. The men become impotent, lose muscle mass and develop osteoporosis. "Now we're seeing patients who have been on hormonal therapy for five, six, eight years with no sign of cancer in their body other than their PSA test," says Dr. Mario Eisenberger, one of the study's co-authors. Were they castrated for nothing?

What the Hopkins researchers found is that both the timing and the speed with which the PSA level rises are critical. Men with the most common tumors (Gleason scores 5 to 7) whose PSA levels rose within two years of surgery and took less than 10 months to double almost always developed life-threatening metastases. Those whose PSA levels rose more than two years after surgery and took more than 10 months to double almost always had cancers that grew too slowly to need further treatment.

It sounds complicated--and it is. But the more you learn about the PSA test, the better able you will be to make informed decisions about your treatment.

To read an abstract of the J.A.M.A. study on the Web, visit www.jama.com You can e-mail Christine at gorman@time.com