RADIATION INCREASES SURVIVAL IN ADVANCED PROSTATE CANCER

October 26, 2010 — Androgen-deprivation therapy (ADT) plus radiation should be the standard treatment approach for patients with locally advanced prostate cancer. According to interim results from the largest randomized study of its kind to date, the addition of radiation therapy significantly reduced the risk for death among this population.

"
We

feel that these results are practice-changing," said Malcolm Mason, MD, lead author of the study and a radiation oncologist at Cardiff University in Wales, United Kingdom. "The standard of treatment for patients with high-risk localized prostate cancer who are fit to receive radiation therapy — which is not every man — should now be combination hormone therapy plus radiation."

Dr. Mason presented his findings at a press briefing held in advance of the American Society for Radiation Oncology (ASTRO) 52nd Annual Meeting. Some of these results were released earlier this year at the American Society of Clinical Oncology (ASCO) annual meeting.

There are now more data available. "We have more information on therapy details that we didn't have at ASCO," explained Dr. Mason. "We are now waiting for the final analysis, which will be available in the next year or so."

Hotly Debated Topic

Dr. Mason emphasized that this is a "hotly debated topic" and that there is much variation in the treatment of men with localized high-risk prostate cancer.

He noted that when the study was launched back in the 1990s, the view was that these men should be treated with hormone therapy alone. Many believed that radiation therapy was likely to be ineffective, and possibly harmful, even though there had been papers published showing benefit at that time.

"The feeling was that the role of radiation therapy had not been established," he said. "We set out to define that role."

The study results thus far indicate that the addition of radiation therapy significantly reduced the risk for death in this patient population, without a significant increase in late treatment toxicity. Patients were followed for a median of 6 years, and the chances of dying from prostate cancer were reduced by 43% among those who received radiation therapy, according to Dr. Mason.

The independent data monitoring committee recommended the release of these results in light of their importance.

Survival Benefit Observed

The primary objective of the study was to evaluate the effect of radiation therapy plus ADT on overall survival in men with locally advanced prostate cancer. A total of 1205 men were randomized from 1995 to 2005 to either ADT alone (n = 602) or to ADT plus radiation therapy (n = 603).

Radiation therapy consisted of 65 to 69 Gy to the prostate, with or without radiation to the seminal vesicles, and, in some patients, of 45 Gy to pelvic nodes. The 2 study groups were well balanced with respect to baseline characteristics, and a protocol-specified second interim analysis on overall survival was conducted in August 2009.

Patients had T3/T4 disease or T2 prostate adenocarcinoma with a prostate-specific antigen (PSA) level above 40 μg/L, or T2 prostate adenocarcinoma with a PSA level above 20 μg/L and a Gleason score of 8 or higher. Secondary end points included disease-specific survival, time to disease progression, and quality of life.

Thus far, 320 patients have died (175 receiving ADT and 145 receiving combination treatment); of this group, 140 died of prostate cancer and/or treatment (89 receiving ADT and 51 receiving combination treatment). The authors found that adding radiation to standard treatment significantly reduced the risk for death (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61 - 0.98; P = .033).

The disease-specific survival HR was 0.57 (95% CI, 0.41 - 0.81; P = .001) in favor of combination therapy, and the estimated 10-year cumulative disease-specific death rates were 23% with ADT alone and 15% with combination therapy.

Serious toxicity rates were similar in both study groups. Dr. Mason reported.

Prostate Cancer Paradox

"This study is of the highest quality of evidence," said ASTRO president and moderator Anthony L. Zietman, MD.

Dr. Zietman, who is from Massachusetts General Hospital in Boston, explained that the "paradox of prostate cancer" has been the ability to cure patients with low-risk disease who "may not need to be cured at all" and the failure to provide adequate treatment for those with more lethal disease.

"This shows that we really can help men with locally advanced disease," he said. "We shouldn't regard them as just needing palliative treatment — they really can be cured."

The study was supported by grants from the National Cancer Institute, the Canadian Cancer Society Research Institute, and by the UK Medical Research Council. Coauthor M.R. Sydes is employed by the UK Medical Research Council. None of the other researchers have disclosed any relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 52nd Annual Meeting: Abstract 3. To be presented