The landmark Radiation Therapy Oncology Group (RTOG) 94-08 clinical trial was the first to demonstrate definitively that the addition of short-term hormones to radiation therapy does not improve survival in men with low-risk prostate cancer. And while a new subgroup analysis of the trial, presented at the 2010 Genitourinary (GU) Cancers Symposium in San Francisco, showed that men with intermediate-risk prostate cancer obtained a significant survival benefit from hormone therapy, more study may be needed to truly judge the merits of androgen deprivation therapy for this group of men, according to experts at the symposium. The 2010 GU Cancers Symposium was cosponsored by ASCO, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

"There are still some questions about whether intermediate-risk patients will benefit from androgen deprivation therapy, since modern advances in radiation therapy that have occurred since the RTOG 94-08 trial began in 1994 allow us to deliver higher doses of radiation with better results," said Christopher Jones, MD, one of the study's principal investigators and a partner at Radiological Associates of Sacramento in California.

Key Data

In the RTOG 94-08 trial, 1,979 patients with localized (mostly T1b-T2b) prostate cancer and a prostate-specific antigen (PSA) level ≤ 20 ng/mL were randomized to radiotherapy alone or to 4 months of flutamide at 250 mg three times a day, monthly goserelin (Zoladex) at 3.6 mg, or leuprolide at 7.5 mg starting 2 months before the initiation of radiotherapy. The dose of radiotherapy delivered to the prostate-66.6 Gy-was consistent with the standard of care in 1994. Median follow-up for patients in both arms was 8.4 years in the hormone-plus-radiotherapy arm and 8.1 years in the radiotherapy arm. Results indicated that for the overall study population, short-term hormone therapy given prior to and during radiation therapy increased a man's chance of survival from 57% to 62%. The 10-year disease-specific survival also increased from 93% to 96% with the addition of hormones. However, men with intermediate-risk prostate cancer seemed to benefit the most from hormone treatment. At 8 years, the overall survival for intermediate-risk patients treated with hormones plus radiotherapy was 72%, compared to 66% for those who received radiotherapy alone (HR = 1.23; 95% CI = 1.02-1.49).

"It's interesting to note that the actuarial death rate from intercurrent disease was similar in both arms, so there was no disadvantage to the addition of hormones," said David McGowan, MD, of the Cross Cancer Institute in Edmonton, Alberta, Canada, another principal investigator for the study. The rates of gastrointestinal and genitourinary toxicities were similar in both arms, he added.

Results Not Definitive

Dr. Jones noted that scientific evidence overwhelmingly supports the use of long-term androgen deprivation therapy in men with high-risk disease. He commented that although the results of the RTOG 94-08 study were not definitive for intermediate-risk patients, many clinicians still consider it wise to add hormonal therapy to radiotherapy for men in this risk group, particularly because hormones do not cause significant toxicity, he said. A newer trial, RTOG 08-15, will provide more evidence about the benefits of adding hormonal therapy to radiotherapy-at currently used doses-for those with intermediate-risk prostate cancer, he added.

"RTOG 94-08 gives us level 1 data, and for the first time showed us that men with low-risk prostate cancer do not benefit from the addition of hormone therapy," commented Deborah Kuban, MD, Professor in the Department of Radiation Oncology at The University of Texas M. D. Anderson Cancer Center in Houston, and Chair of the GU Cancers Symposium. "But we don't know if giving hormone therapy to intermediate-risk men in this trial simply made up for the lower doses of radiation used at the time. We do know that androgen deprivation is a very potent and effective adjunct to radiation," she said. "But going forward, we will need to know more about whether it is really necessary for men with intermediate-risk prostate cancer and subgroups of men with intermediate-risk cancers when higher doses of radiation are given. It may be that intermediate-risk patients with less bulky tumors may not need hormone therapy," she noted.

For additional data on androgen deprivation plus radiotherapy in locally advanced prostate cancer, watch for abstracts CRA4504 and 4505, being presented June 6 at the ASCO Annual Meeting.

Reference

1. McGowan D, Hunt D, Jones C, et al: Effect of short-term endocrine therapy prior to and during radiation therapy on overall survival in patients with T1b-T2b adenocarcinoma of the prostate and PSA equal to or less than 20: Initial results of RTOG 94-08. 2010 Genitourinary Cancers Symposium. Abstract 6. Presented March 5, 2010.