Timing of Treatment Cuts Prostate Cancer Deaths Five-Fold

Findings in today's NEJM suggest major change in how men are treated after prostatectomy

December 08, 1999

Men who have prostate cancer which has spread to the lymph nodes are five times less likely to die of the disease if they start hormonal treatment immediately after radical prostatectomy than if such treatment is started only after the disease recurs, says a study in today's New England Journal of Medicine. For patients with advanced prostate cancer, doctors employ therapies which stop testosterone from stimulating the cancer cells - but when to administer these therapies has been a controversy since the 1970's when the Veterans Administration Cooperative Urological Research Group stated that early treatment did not prolong survival.

"It's been the general dogma that hormonal therapy could be safely withheld until the disease was visibly recurring," explains Edward Messing, M.D., lead author of the study and chair of the Department of Urology and deputy director of the University of Rochester Cancer Center. "Our study shows something very different. Early treatment meant a significant improvement in survival for our patients."

About 5-10 percent of men who undergo a prostatectomy are found to have cancer cells spread to their lymph nodes, but with molecular testing likely to become readily available in just a few years, doctors will be able to detect minute amounts of prostate cancer cells in the lymph nodes. According to Messing, these men will also benefit from immediate treatment.

"In recent years, the availability of alternate forms of hormonal therapy has renewed interest in finding the optimal timing for delivering hormonal therapy," Messing explains. "Since that timing is controversial we designed the tightest study we could, using patients who showed little or no evidence of cancer after prostatectomy, but were known to be at very high risk for disease recurrence because their cancers had already spread to lymph nodes."

Unlike previous studies, 80 percent of the men enrolled showed no detectable sign of any cancer recurring after the surgery, giving researchers an excellent starting point from which to compare the men later. Other studies have used patients having much larger amounts of cancer and often studied the combined effects of drugs and radiation.

Messing and his colleagues in the Eastern Cooperative Oncology Group divided 98 men who underwent radical prostatectomies and whose cancer had spread to their pelvic lymph nodes, into two groups. One group was given the choice of having their testicles removed or receiving regular injections that inhibited the secretion of testosterone. The men in the other group were kept under observation until there were definite signs of the cancer recurring, then they were also given similar hormonal treatment.

After more than seven years, 41 of the 51 men in the delayed-treatment group experienced a recurrence of cancer, while only 7 of the 47 men immediately given therapy showed similar signs. In addition, 18 men in the delayed-treatment group died by the end of the study: 16 from prostate cancer. In the early-treated group, only 7 men died: three from prostate cancer.

The hormonal therapy used in the study is a drug commercially known as Zoladex. This was given to the men every three months as an injection. Messing plans to study how the timing of hormonal therapy affects other groups of men with prostate cancer.

This study was funded by the National Cancer Institute, the National Institutes of Health and the Department of Health and Human Services.

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