For Men at Risk, Radiation Combined With Temporary Hormonal Therapy 

Here's a statistic: About half of American men with prostate cancer are treated with some form of radiation therapy. But afte rthat, it's a bit harder to generalize - and more complicated to determine which men will need additional treatments in combination with the radiation. For most men -those diagnosed with early-stage, low-riskcancer - radiation therapy alone is enough,says Theodore L. DeWeese, M.D,. Chairman of the Department of Radiation Oncology and Molecular Radiation Science, and professor of radiation oncology, oncology andurology. "These men rarely experience a clinical recurrence of cancer after treatment. But some men are diagnosed with more aggressive disease, and are at greater risk for recurrence."

Which men, then, are at extra risk? The Partin Tables (discussed in the Winter 2005 issue of Discovery, and the Winter 2003 issue of Prostate Cancer Update, both Brady publications), based on the course of prostate cancer in thousands of men, can predict the likelihood of cancer recurrence with 95-

What about the men with intermediate risk of recurrence?Can the combined treatment help them,as well? The latest evidence signals a hearty "yes."

percent accuracy. One surprising revelation of such tables, says DeWeese, is that "a substantially greater number of patients than we previously believed actually have cancer that is already outside the prostate at diagnosis - even though it is not able to be detected by physical examination or scans."With the help of such data, "we can group patients into low-risk, intermediate-risk and high-risk groups for tumor recurrence," he adds. This is very important, because at fiveyears after treatment, men with intermediate-risk disease have a likelihood of bio-chemical recurrence - the return of PSA -of about 40 to 50 percent. The odds ofrecurrence for men with high-risk disease:65 to 75 percent. "Clearly, for patients with intermediate and high-risk disease, we need better therapeutic approaches."

One approach that immediately suggests itself is based on prostate cancer's sensitivity to hormonal therapy (suppressing the male hormones, or androgens). Can hormonal therapy make radiation treatment more effective for men with localized prostatecancer? For men at high risk of recurrence,"a number of studies have been conducted to test the benefit of this combined treatment," comments DeWeese, "and each trial has shown a significant advantage in improving cancer outcome." This includes controlling the cancer in the pelvis, limiting the risk of developing metastatic disease, and in one trial, prolonging life. These studies "strongly argue" for the combined approach in high-risk men.

But what about the men with intermediate risk of recurrence? These men have stageT1b-T2b disease, with a Gleason score of 7 or a PSA between 10 and 20 ng/ml. Can the combined treatment help them, as well? The latest evidence signals a hearty "yes" totemporary androgen suppression for these men, too. In a recent study, reported in the Journal of the American Medical Association, men with primarily intermediate-risk cancer were treated with either a short course (six months) of androgen suppression in addition to radiation therapy or with radiation therapy alone. "This study is very important," says DeWeese, "because it is the first trial to demonstrate that men with intermediate-risk disease who receive a short course of androgen suppressive therapy plus radiation achieve a significant increase in overall survival when compared to men treatedwith radiation therapy alone."

However, DeWeese notes, "the radiation doses used in this study were relatively low by today's standards. At Johns Hopkins, we routinely administer higher radiation doses to the prostate and areas around it," using techniques such as intensity modulated radiation therapy (IMRT) to deliver these higher doses safely. "This is more likely to eradicate prostate cancer cells, and to improve control of cancer. So it might be that the low radiation dose used in this study could have resulted in lesser control of cancer than if higher doses had been used." It is not clear how higher doses of radiation affect the hormonal therapy. Could this also mean that the hormonal therapy is only helpful with lower doses of radiation? "While this is a possibility, it cannot be easily answered with one or even several studies," says DeWeese."We will continue to use higher radiation doses along with androgen suppression in men with intermediate-risk disease, because it has been shown to be beneficial and to increase survival."

However, DeWeese adds, the field of radiation therapy is constantly evolving. "As we are able to deliver significantly increasing doses of radiation with unprecedented accuracy and precision, whether all patients will ultimately require hormonal therapy is not clear."


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