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The addition of a short course of hormone therapy to radiation improves outcomes for patients with intermediate-risk, early-stage prostate cancer.
However, considering the evolution that has occurred in radiation techniques since the study was launched, the implications of the outcomes for modern treatment are unclear, said Christopher U. Jones, MD, a study author and radiation oncologist at Sacramento, CA-based Radiological Associates of Sacramento. Dr. Jones and colleagues presented study results from protocol RTOG 94-08 at the American Society for Radiation Oncology annual meeting.
RTOG 94-08, which was launched in October 1994, enrolled patients with biopsy-proven T1b-T2b adenocarcinoma of the prostate and a PSA ≤20.0 ng/mL. Through April 2001, a total of 1,979 men were randomized to receive radiation therapy alone (66.6 or 68.4 Gy) or with a 4-month course of androgen suppression started 2 months prior to radiation.
Benefit in intermediate-risk group
"RTOG 94-08 represents one of the largest clinical trials of prostate cancer therapy ever completed, but the relevance of its results in our modern era of radiation therapy is unclear," he said. "Now, radiation doses for locally confined prostate cancer are about 15% to 20% higher, and a number of studies show the higher doses are associated with better outcomes. Now, protocol RTOG 08-15 is under way to investigate whether intermediate-risk patients with locally confined prostate cancer being treated with modern radiation methods still benefit from a short course of hormone therapy."
RTOG 94-08 was undertaken because evidence from earlier studies showed neoadjuvant androgen deprivation improved survival among men with more advanced prostate cancer undergoing radiation therapy.
"Determining whether hormone therapy offered an advantage in patients with earlier-stage prostate cancer was important because with the advent of PSA screening, many more men were being diagnosed with early-stage disease. However, recognizing that these patients generally had a better prognosis, we wanted to avoid exposing them to the risks of prolonged androgen deprivation, and so a short-course regimen was studied," Dr. Jones explained.
Hormone therapy in RTOG 94-08 consisted of flutamide (Eulexin), 250 mg three times daily, plus either monthly subcutaneous goserelin acetate (Zoladex), 3.6 mg, or intramuscular leuprolide (Lupron), 7.5 mg. The total radiation dose was 66.6 or 68.4 Gy.
The post hoc outcomes analysis stratifying men into risk subsets was conducted using the National Comprehensive Cancer Network definitions for low-risk (Gleason score ≤6 with a PSA ≤10.0 ng/mL and stage T2a or less), intermediate-risk (Gleason score of 7 or Gleason score ≤6 and either PSA 10.0 to 20.0 ng/mL or stage T2b), and high-risk (Gleason score 8 to 10) disease.
ADT use in low-risk men not supported
"Based on our risk subset analysis, this study does not support the routine use of short-course androgen deprivation for patients with low-risk prostate cancer," Dr. Jones said. "We had too few men within the high-risk group to analyze a potential benefit of hormone therapy. Now, however, these men would receive a more aggressive course of hormonal treatment than what was administered in the study."
Based on available follow-up, the 4-month course of hormone therapy had an acceptable safety profile. Men treated with hormone therapy had the expected short-term side effects. However, the regimen did not increase the risk of death or intercurrent disease, and there were no significant differences between the two groups in early or late gastrointestinal or genitourinary toxicity.
"However, we still need to do a formal late toxicity analysis to evaluate the recovery of sexual function after hormone therapy," Dr. Jones said.