Estimating Risk Of Advanced Cancer After Radical Prostate Surgery

New Formula May Help Patients and Physicians Choose Further Therapy

May 15, 1999. While prostate removal cures most men of their prostate cancer, more than a third show a rise in their prostate specific antigen (PSA) levels in the 10 years following surgery, an early sign that cancer may be returning. Now, in the largest and longest study of its kind, urologists at Johns Hopkins have developed a method for assessing the risk these men have for developing metastatic cancer.     

 "The first thing patients want to know after their PSA rises following surgery is how long they have to live," says Patrick Walsh, M.D., Hopkins' chief of urology, who removed the prostates of the 1, 997 patients in the study. "And the first thing doctors want to know is what type of follow-up treatment the patient needs. Up until now, there hasn't been any sure way to know."
      In the most extensive follow-up study on the natural course of prostate cancer after surgery, Walsh and his colleagues compiled 10,000 patient-years of data from 1982 to 1997. The men were followed for an average of 5.3 years. From this information, Walsh's team developed a chart physicians and patients can use to pinpoint the risk for developing metastatic cancer, which in men with prostate cancer typically invades the bones.
      "Doctors used to say, You've recurred, but we aren't sure what that means," says Alan Partin, Ph.D., a co-author on the study, which appeared in the May 5, 1999, Journal of the American Medical Association [see link in sidebar]. "Now they can say, You've recurred, and we know your risk for developing advanced cancer."
      While outcomes depend partly on whether removal of the prostate is appropriate for the patient in the first place and on quality of surgery and after care, the formula pinpointed by this Hopkins study should hold across the board, wherever the surgery is done. The formula cannot predict how many men will experience recurrence after surgery at other medical centers. Butif recurrence happens, what counts is not where the surgery was done but what the disease is doing
Gleason, Time Till PSA Rise, PSA Doubling Time
      The chart places men into different risk groups using three common measures: the so-called Gleason score of the removed prostate (a measure of the cancer's severity and aggressiveness); timing of the rise in PSA level (either before or after two years post-surgery); and the length of time it took the PSA level to double (either greater or less than 10 months).
      A man in the lowest risk group (with a moderately severe tumor, PSA recurrence after two years post-surgery, and PSA doubling time greater than 10 months) has a 95 percent chance of being metastases-free three years after the PSA recurrence; an 86 percent chance at five years; and an 82 percent chance at seven years.
      "When men see their PSA levels rise again, they think that means the cancer is back and they need to get treated aggressively right away. But that isn't always the case," says Mario Eisenberger, M.D., a Hopkins oncologist and study co-author. "Patients may live for years without having the cancer spread. This information will better equip doctors and their patients to decide who is a candidate for additional therapy."
      The study is critical for future drug research as well, says Partin, because it provides essential baseline data. "Before, it was difficult to know if a drug was helping, because you couldn't be sure what the disease would have done on its own," he says. "Now, researchers can compare their treatment groups with our study group and tell if their treatment is improving survival."
Other findings from the study:

Men who experienced rising PSA levels (304 out of 1,997) remained free from metastatic cancer an average of eight years.

After developing metastatic cancer, as confirmed by imaging techniques like bone scans, the average time to death was five years. However, men who developed metastases eight or more years following surgery had a much better outlook.

At 15 years post-surgery, a projected 82 percent of men will still be free from metastatic cancer and considered cured.

These projections are based solely on surgery performed by Walsh's team at Johns Hopkins.