ANN ARBOR, Michigan--The addition of androgen ablation to radiation
therapy led to significant improvement in the rate of local failure,
distant failure, and disease-free survival, but not overall survival,
in men with large-volume, low-grade, locally advanced prostate
Adjuvant hormonal treatment improved 5- and 8-year outcomes in the
multicenter RTOG trial. However, the benefits were limited to
patients whose tumors were Gleason grade 2 to 7, Miljenko V.
Pilepich, MD, reported at ASCO.
The findings came from a randomized trial of 471 men who had locally
advanced prostate cancer stages T2-T4 and no evidence of distant
metastases. To qualify for the study, the product of tumor dimensions
had to be 25 or more.
Only 8% of patients had positive lymph nodes, a low rate that might
have reflected the fact that nodal status was evaluated predominantly
on the basis of CT scans, said Dr. Pilepich, a radiation oncologist
at St. Joseph Mercy Hospital, Ann Arbor, Michigan.
PSA testing was not available when patient accrual began in 1987 and
was added to the workup only in the latter stages of investigation.
For the entire study population, 30% of patients had stage T2 cancer
and 70% had stages T3-4.
The patients were randomized to receive standard radiation therapy or
radiation plus 4 months of hormonal treatment, beginning 2 months
before the start of radiation. Hormonal therapy consisted of 3.6 mg
of goserelin (Zoladex) every 28 days plus 250 mg of flutamide
(Eulexin) three times a day. The radiation dose was 44 to 46 Gy to
the regional lymph nodes and 65 to 70 Gy to the prostate.
Median follow-up has reached 6 years for the entire study population
and 7 years for patients who remain alive. The investigators defined
local disease progression as at least a 50% increase in the product
of tumor dimensions. Systematic biopsy was not standard when the
trial began, and biopsies were performed only as indicated.
Local Failure Rates
At 5 years, 22% of the combined-treatment arm had experienced local
failure, compared with 35% of the control arm. Eight-year local
failure rates were 31% and 44%, respectively, for combination
treatment and controls. The overall trend significantly favored
combination therapy (p = .005).
Distant failure occurred in 29% of the combination arm at 5 years and
35% at 8 years. The distant failure rates for patients who received
only radiation therapy were 39% and 45%, respectively, at 5 and 8
years (p = .04).
Disease-free survival was 49% at 5 years and 29% at 8 years in
patients who received hormonal therapy plus radiation. At the same
time intervals, the disease-free rates were 34% and 21%,
respectively, in patients who received radiation therapy alone (p = .005).
Overall survival also favored patients who received the combination:
97 patients in the combination arm have died vs 119 in the group that
received radiation therapy only. However, the difference has not yet
Evaluation by tumor grade showed substantial differences between
patients whose tumors were Gleason grades 2-7 vs Gleason 8 or higher.
Patients with higher Gleason grades derived no significant benefit
from combination therapy for any of the survival parameters.
"Looking at the data in this and other RTOG studies, we can
conclude that a brief course of hormonal management, given before and
during radiotherapy, has a profound effect on tumor progression in
Gleason 2-7 patients," he said. "However, to exert its
beneficial effect on tumor progression and survival in Gleason 8-10
patients, hormonal management must be administered over a much longer
period, at least several years."