High-risk localized prostate cancer patients treated with a combination of hormone therapy and external-beam radiation have substantially better survival rates than those on hormone therapy alone, according to interim results of the largest randomized study of its kind to date.
The findings were presented at the plenary session of the American Society for Radiation Oncology (ASTRO), and updated interim findings presented in June at the ASCO Annual Meeting.
In the study, 1,205 men with high-risk prostate cancer, treated between 1995 and 2005 in the United States, the United Kingdom, and Canada, were randomly assigned to receive hormone therapy or a combination of hormone therapy and high-beam external radiation treatment. The men were followed for at least six years, on average, but the trial's endpoint follow-up was seven years.
The multicenter randomized trial examined cancer deaths in patients with a high risk of cancer recurrence who received external-beam radiation treatment and ongoing androgen-deprivation therapy (ADT), with those receiving hormone therapy alone.
The National Cancer Institute of Canada, the UK Medical Research Council and the Southwest Oncology Group jointly conducted the research.
ADT lowers the level of male hormones to shrink the prostate or slow down the growth of prostate cancer. Among the men, 602 were assigned to receive ADT and 603 received ADT plus high-beam radiation.
Adding radiation to hormone therapy significantly reduced the risk of death, the teams found—51 deaths in patients who received combined therapy compared with 89 deaths in the ADT group, after seven years. The 10-year cumulative disease-specific death rates were estimated at 15% with ADT and radiation, vs 23% for those receiving ADT alone.
Special Permission to Report Interim Data
The data were considered so significant that the researchers were given permission to report their interim findings.
“This is the largest study ever in men, and the results of a planned interim analysis of the data,” Malcolm Mason, MD, lead author of the study and Cancer Research Professor of Clinical Oncology at Cardiff University, in Wales, said at a news briefing.
“We found the combination reduced the chance of death from prostate cancer by 43 percent. We feel these results are practice changing.”
The final analysis will be released after further follow-up with the patient group, said Dr. Mason, a member of the Editorial Board of OT's UK Edition.
“Research by my colleagues in Canada and ourselves suggests that a large number of men on both sides of the Atlantic are still getting hormone therapy only. There may be legitimate reasons why some patients are not getting radiotherapy and hormone therapy—they may not be suitable for radiotherapy—but really and truly this ought to be changing practice now.”
Treatment Varies Widely
There is significant variation in how localized, high-risk prostate cancer is treated. Although combined hormone and radiation therapy has increased in recent years, it remains controversial and most patients are treated with hormone therapy alone.
Treatment guidelines issued by the National Comprehensive Cancer Network recommend combined external radiation-hormone therapy for high-risk prostate cancer patients, while the American Urological Association recommends that physicians advise high-risk patients that adding high-beam radiation to hormone treatment can boost survival.
In external-beam radiation therapy, radiation beams are directed through the skin to the prostate and the immediate surroundings to destroy the main tumor and any nearby cancer cells. The treatments are outpatient and generally painless, much like receiving an x-ray. Side effects most often reported are mild bowel and bladder problems. Patients typically do not experience hair loss or nausea like with some other treatments.
A growing number of studies have reported similar efficacy and reduced mortality from combining radiation and hormone therapy in men with high-risk prostate cancer.
For example, a large Phase III study by Scandinavian researchers, published in The Lancet in January 2009, is one such study. It found that 10-year prostate-cancer-specific mortality in patients treated with hormone and radiation was half that in those who received hormone therapy alone.
The researchers randomized 875 men with localized advanced prostate cancer from 47 treatment centers in Norway, Sweden, and Denmark. Between February 1996, and December 2002, a total of 875 patients with locally advanced prostate cancer were assigned to hormone therapy alone (3 months of total androgen blockade followed by continuous endocrine treatment using flutamide), or the same endocrine treatment combined with radiotherapy (436 patients).
After a median follow-up of 7.6 years, 79 men in the hormone group and 37 men in the ADT-plus-radiotherapy group had died of prostate cancer. The cumulative incidence at 10 years for prostate-cancer-specific mortality was 23.9% in the endocrine-alone group and 11.9% in the combined-therapy group (difference of 12.0%, for a relative risk of 0.44.
Asked for his opinion for this article, Mack Roach III, MD, Professor and Chair of the Department of Radiation Oncology at the University of California, San Francisco, Comprehensive Cancer Center, said that he believes there is now sufficient evidence for combined radiation and hormone therapy to be adopted more widely in treating patients with locally advanced prostate cancer.
“This is one of the most important studies to date in prostate cancer because it demonstrates that the combination improves survival,” he said. “There are now three large studies that have shown this, but this one is especially important because it shows that radiation works with more aggressive hormone therapy.”
He noted that even though the NCCN guidelines recommend that physicians discuss combined therapy with patients, hormone therapy is entrenched as preferred treatment.
“The first studies showed benefits with hormone therapy, and it has become in some ways the gold standard, with level one data, so it has become accepted as an effective treatment. But now we know for certain that combining radiation with hormone therapy is better than either one alone.”
Unfortunately the conclusions released by the Agency for Healthcare Research and Quality regarding the role of radiotherapy in prostate cancer patients were unable to consider the newer data on combined therapy—and in particular, the importance of external-beam radiotherapy in high-risk prostate cancer patients, Dr. Roach continued.
“The suggestion that the evidence for radiotherapy is low to medium is in error. The bottom line is that we now have three comprehensive studies showing that combining radiation with hormone therapy improves survival in these men with prostate cancer, and three studies showing that postoperative radiotherapy improves outcome after radical prostatectomy.
“We are learning more, step-by-step, that radiotherapy plays a very important role in the management of prostate cancer patients.”