Major Finding: Compared with hormone therapy alone, a combination of androgen deprivation and pelvic radiation significantly reduced the chance of prostate cancer death by 43% in men with locally advanced disease.
Data Source: A randomized phase III trial in 1,205 patients, 6 years after treatment,
Disclosures: The trial was sponsored by the National Cancer Institute of Canada's Clinical Trials Group, the U.K. Medical Research Council, and the Southwest Oncology Group in the United States. Dr. Mason reported no financial disclosures with regard to the trial. One of the coauthors (Matthew Sydes) is an employee of the U.K. Medical Research Council.
SAN DIEGO — A combination of external-beam radiation and hormone therapy should become the gold-standard treatment for men with locally advanced prostate cancer, if the interim analysis of a large randomized study holds up during its follow-up period.
The study's data safety and monitoring committee recommended releasing the results after an interim analysis found a 43% decrease in the risk of prostate cancer death among the combination group compared with those who received only androgen deprivation, Dr. Malcolm Mason said during a press briefing.
“If the figures from the interim analysis are similar to the final analysis, we would expect a 43% reduction in the chance of death from prostate cancer in men with this [combination regimen],” said Dr. Mason, head of oncology and palliative medicine at Cardiff University, Wales, and the study's primary author.
“This would translate into a reduction in the chances of death from prostate cancers in many thousands of men worldwide,” Dr. Mason said.
The study comprised a total of 1,205 men who were treated from 1995 to 2005.
The preplanned interim analysis included data that were collected up through the end of 2008. The median follow-up at that point was 6 years. Final results are expected in either 2011 or 2012, according to Dr. Mason.
The groups were evenly split between the two treatment regimens: 602 men received androgen deprivation therapy only, which consisted of bilateral orchidectomy or lifelong luteinizing hormone–releasing hormone (LHRH) agonist. The remainder of the patients (603 men) had a combination of androgen deprivation therapy and external-beam radiation (65-69 Gy to the prostate and/or seminal vesicles, with or without pelvic nodes).
The majority of the participants had T3 or T4 cancer (1,057); 119 had T2 cancer with a prostate-specific antigen level of more than 40 mcg/L; and the rest had T2 cancer with a lower PSA level (more than 20 mcg/L) and a Gleason score of 8 or higher.
None of the patients in the study had metastatic disease.
The primary end point was overall survival. Secondary end points were disease-specific survival, time to progression, and quality of life.
At the time of the interim data analysis, full follow-up information was available on 90% of the patients. At that time, 320 (26.5%) had died from any cause: 175 in the hormone therapy–only group (55%) and 145 in the combination therapy group (45%). The addition of radiation therapy to hormone therapy resulted in a significant 33% decrease in the overall risk of death (hazard ratio 0.77, P = .033).
Deaths from prostate cancer and/or treatment numbered 140: 89 (63.5%) in the hormone therapy–only group and 51 (36%) in the combination therapy group.
This translated to a significant 43% reduction in the risk of dying from prostate cancer (HR 0.57, P = .001).
Extrapolating these data out to the final 10-year follow-up point, the researchers predicted that the rate of disease-specific death would be 15% with a combination of hormone therapy and radiation therapy and 23% with hormone therapy alone – again a statistically significant difference.
Toxicity rates of grade 2 or higher and gastrointestinal toxicity were similar in both arms of the study, with proctitis occurring in 1% of the hormone therapy group and 2% of the combination therapy group.
“In addition to the significantly decreased risk of dying from prostate cancer, the toxicity was not a major issue,” Dr. Mason observed during the press briefing.
“For both of these reasons, we feel that these results are practice changing, and that the treatment standard for men with high-risk prostate cancer who are fit to undergo radiation therapy should be a combination of hormone therapy and radiation therapy,” according to Dr. Mason.