If a man develops an elevated PSA level (more than 0.2) after surgery, he is considered to have recurrent disease — and “recurrence” is a dreaded word for men who have undergone treatment for prostate cancer.But a new Brady study shows that not all recurrence, like not all cancer, is equal, and that not all men need aggressive treatment— or any treatment right away — if cancer comes back.

Brady investigators have developed reference tables for physicians and patients that help determine which men are going to be in trouble and in need of more aggressive treatment, and which men have a slow-growing cancer that may not cause trouble for years, are relatively safe and can be carefully watched.

The tables estimate the risk of prostate cancer-specific survival at five, ten, and 15 years after biochemical recurrence (the return of detectable levels of PSA in theblood, even if there are no other symptoms of cancer).

The difference between high- and low-riskrecurrence can mean a matter of years, says urologist Stephen J. Freedland, first author of the study, which was published in the Journal of the American Medical Association. Some men in the low-risk group lived more than 16 years after their cancer returned, with no sign that the cancer had spread to bone. If caught early enough, prostate cancer can be cured by radical prostatectomy. However, as many as one-third of those who undergo surgery will eventually show signs that the cancer has recurred, Freedland explains. This investigation — an update of another Brady study, published in 1999 by Charles R. Pound, M.D., and colleagues —studied 379 men who underwent a radical prostatectomy at Hopkins between 1982 and 2000 and developed a rising PSA after surgery. (The study did not include men who received radiation treatment before surgery or hormonal therapy.) “We looked at the long-term outcomes of these men over five, ten, and 15 years,” Freedland explains, “to see who died from the cancer and who was alive and well.” The scientists found that the severity of recurrence depended on three risk factors:

PSA doubling time. Based only on the PSA values during the first two years after PSA reappeared, how long did it take for the PSA level in the blood to double? Less than three months, between three and nine months, from nine to 15 months, or greater than 15 months?

Gleason score: Is it 7 or lower, or Gleason 8t o 10? and

Time from surgery to the return of PSA. Was it within three years, or afterward? If a man’s PSA doubled in less than three months, his risk of dying from prostate cancer was much higher than that of a man whose PSA doubling time was more than a year. The same holds true for the time from surgery to the return of PSA: If PSA appeared on a blood test within three years after surgery, that man is at higher risk than is a man whose PSA returns in five years.

The differences in risk turned out to be great, Freedland says. “It is amazing to me that for a man who has all the low-risk features — if his PSA doubling time is greater than 15 months, his Gleason score is below 8, his PSA comes back after three years — his odds of being alive 15 years later are 94 percent.” These men do not need treatment, he adds. “If we know that 94 percent ofthese men are alive and well 15 years aftersurgery with no further treatment, anythingwe do to treat them is unlikely to improve on that, and probably would only affect the quality of life.”

In contrast, for a man at highest risk — a man whose doubling time is less than three months, whose PSA returns within three years, and whose Gleason score is 8 or higher— the odds of being alive 15 years after surgery were less than one percent. These are the men who are candidates for further treatment, says Freedland, “including clinicaltrials and starting more aggressive therapy.”

Estimate (and 95% Confidence Interval) of the risk of prostate cancer specific survival after biochemical recurrence following radical prostatectomy

A: 5-year estimate

B: 10-year estimate

C: 15-year estimate

Other authors of the study include Brady scientists Alan Partin, Patrick Walsh, Mario Eisenberger, Leslie Mangold and Elizabeth Humphreys, and from the University of Southern California, Frederick J. Dorey.