CHICAGO — The addition of hormone therapy to radiation improves overall survival in men with locally confined prostate cancer, but the benefit appears to be concentrated in intermediate-risk patients, according to initial results from the largest prostate cancer treatment trial to date.
The overall survival rate among the 1,979 men in the Radiation Therapy Oncology Group (RTOG) 9408 trial was 62% with combined therapy and 57% with radiotherapy alone at 8 years, Dr. Christopher U. Jones reported in a late-breaking abstract at the annual meeting of the American Society for Therapeutic Radiology and Oncology.
Intermediate-risk men who received 4 months of androgen suppression plus radiotherapy had the most pronounced benefit, with an overall survival rate of 72% vs. 66% for their radiation-only controls. The overall survival rate was 66% and 58%, respectively, in high-risk men and 76% compared with 73% in low-risk men.
RTOG 9408 is “a landmark, practice-changing study,.” said Dr. Matthew R. Smith, of the department of hematology/oncology, Massachusetts General Hospital, Boston. It provides “the first compelling evidence of a survival benefit for short-term androgen deprivation therapy in this intermediate-risk subgroup” treated with conventional radiation, he said. The number needed to treat was 17.
The results of RTOG 9408 had been eagerly anticipated because androgen-deprivation therapy has been widely adopted in men with localized disease, including those at low risk, despite the lack of a compelling survival benefit and emerging evidence of treatment-related morbidity including decreased bone mineral density, greater risk for clinical fractures, and increased triglycerides and insulin sensitivity, Dr. Smith said.
“RTOG 9408 definitively establishes that there is no benefit for androgen deprivation therapy in patients with low-risk disease,” he said. “Cancer control rates are outstanding with both conventional and high-dose radiation therapy in this low-risk group. Unquestionably this is a setting where less is more.”
The trial does not answer whether androgen deprivation is necessary in patients with intermediate-risk disease treated with more modern high-dose radiation techniques, he added. This question will be addressed in other trials, including the recently opened RTOG 0815 trial.
Patients in the current trial were enrolled from October 1994 to April 2001, and randomized to hormones plus radiotherapy (987 patients) or radiotherapy alone (992). All received 66.6 Gy of radiation, a dose slightly lower than that currently used with newer techniques such as intensity-modulated radiation therapy. Androgen deprivation therapy was administered for 2 months before and 2 months during radiation.
At baseline, patients had T1b-T2b adenocarcinoma of the prostate and a prostate-specific antigen (PSA) level of 20 or less. Median age was 71 years.
The low-risk group included 685 patients with a Gleason score of 6 or less, a PSA of 10 or less and no T2b disease. The 1,068 intermediate-risk patients had a Gleason score of 7 or a Gleason of 6 or less and either a PSA of 10-20 or T2b disease. The 226 high-risk patients had a Gleason score of 8-10.
The addition of short-course hormones to radiation did not increase the risk of death from intercurrent disease, said Dr. Jones, a radiation oncologist in Sacramento, Calif.
The actuarial 10-year death rate from intercurrent disease, excluding deaths from prostate cancer, was 35% in the combination arm and 37% in the radiation-only arm.
Dr. Jones reported no conflicts of interest.
The study was supported by grants from the National Cancer Institute in Bethesda, Md.