BOSTONShort-term hormone therapy may benefit patients with
localized intermediate- and high-risk prostate cancer, according to
three retrospective studies presented at the American Society for
Therapeutic Radiology and Oncology (ASTRO) annual meeting.
While the authors said that their results support the use of
short-term androgen ablation in these patients, they emphasized that
their results do not carry the same weight as the recommendation,
based on randomized trials, that long-term hormone suppression be the
treatment standard for patients with locally advanced prostate
The consensus was that validation for hormone therapy in patients
with localized disease might come from two prospective randomized
clinical trials being conducted by the Radiation Therapy Oncology
Group and Dana-Farber Cancer Institute. Both studies are nearing completion.
Anthony V. DAmico, MD, PhD, chief of genitourinary radiation
oncology, Dana-Farber Cancer Institute, expressed the hope that his
study would bolster the practice of physicians who now give hormone
therapy even though androgen deprivation has not yet been proven
conclusively to work in patients with localized disease.
Thats why the study was doneto provide some
support, but not conclusive evidence, that it may help, he
said. Without randomized trials, no conclusions can be made.
Dr. DAmico, associate professor of radiation oncology, Harvard
Medical School, reported on a retrospective cohort study of 1,586 men
with clinically localized prostate cancer treated between January
1989 and August 1999.
All received external beam radiation therapy, but only 276 also
received androgen suppression therapy for 6 months2 months
before, 2 months during, and 2 months after radiation therapy. The
main outcome studied was prostate-specific antigen (PSA)-failure-free
survival after 5 years.
For low-risk patients, hormone therapy did not make a difference
statistically. Five-year PSA-failure-free survival was 92% among
those who had radiation therapy plus androgen suppression therapy and
84% among those who had radiation therapy only (P = .09).
Among intermediate-risk patients, however, 86% of those given
radiation therapy plus hormone therapy were free from PSA failure
after 5 years, compared with 62% of the radiation-therapy-only
patients (P = .0008).
High-risk patients also did better with hormone therapy than without
it. Slightly more than two thirds (67%) of the group receiving
radiation therapy plus hormone therapy achieved 5-year
PSA-failure-free survival vs less than half (43%) of those who had
radiation therapy without hormone therapy (P = .009).
One limitation of the study, Dr. DAmico said, was that the
median follow-up for patients receiving radiation therapy plus
hormone therapy was shorter (by 2 to 6 months depending on the risk
group) than for those who received radiation therapy alone.
Another concern, he said, was the definition of intermediate risk by
PSA level, biopsy Gleason score, or the 1992 American Joint
Commission on Cancer (AJCC) clinical T stage used by other groups
studying hormone therapy.
I get worried when people define intermediate risk as any one
of these factors or high risk as any two, he said. With
these definitions, an intermediate-risk patient can have a PSA of 25
ng/mL and a Gleason of 6, and a high-risk patient can have a PSA of
12 ng/mL and a Gleason of 3+4 equal to 7. That doesnt make
sense to me.
Dr. DAmico said: It is possible that the addition of
hormones in intermediate- and high-risk patients, as defined, may
lead to a long-term benefit in outcomes, but it is not
Low-Risk Patients Dont Benefit
Patrick Kupelian, MD, of the Cleveland Clinic Foundation, also looked
at biochemical relapse-free survival in a study of 974 men with
localized prostate cancer treated with external beam radiation
therapy between 1986 and 1999. One fourth (247) of the patients
received hormones for 6 months or less. Median follow-up was 43 months.
The researchers found that low-risk patients were least likely to
have received hormone therapy and that the few who did showed no
significant benefit, compared with those who did not. The 5-year
biochemical-relapse-free survival rate for low-risk patients was 94%
for those receiving radiation therapy plus androgen suppression and
81% for those who received radiation therapy only.
Based on these results, but emphasizing that longer follow-up is
necessary, the authors recommended against giving hormone therapy to
low-risk patients. So far, as far as we can tell, Dr.
Kupelian said, giving hormones to low-risk patients only adds
toxicity to the treatment. Considering the cost of the treatment and
its potential side effects, such as hot/cold flashes and loss of
libido, hormonal therapy shouldnt be offered as an option for
For intermediate- and high-risk patients, however, the addition of
hormone therapy made a significant difference and was recommended by
the researchers. In the intermediate-risk group, 98% of those who
received hormone therapy, but only 56% of the radiation-therapy-only
group, met the 5-year goal. Among high-risk patients, the rates were
85% and 30%, respectively.
Radiation dose also was an important factor, Dr. Kupelian said.
Patients receiving hormone therapy also received higher radiation
doses88% had doses higher than 72 Gy. Comparing the dose
groups with or without hormones, there were trends, he said,
but they did not reach statistical significance in this study.
Hormones Plus Brachytherapy
Hormone therapy also showed good results in a study of patients
treated with permanent radioactive seed implantation (brachytherapy)
alone or in conjunction with androgen suppression.
Lucille N. Lee, MD, and her colleagues in the Radiation Oncology
Department, Mount Sinai School of Medicine, New York, reviewed the
records of 201 patients treated from October 1990 to September 1998
for moderate- to high-risk prostate cancer.
Moderate risk was defined as having one of the following risk
factors: PSA greater than 10 ng/mL but less than 20 ng/mL, Gleason
score of 7, or stage T2b. High risk was defined as having two or more
of these risk factors, or PSA greater than 20 ng/mL, Gleason of 8 to
10, or stage T2c-T3.
Two thirds of the patients underwent androgen suppression for 3
months prior to brachytherapy and for 2 to 3 months afterward. Median
follow-up was 42 months.
Hormone therapy was the most significant factor associated with
an improved outcome, Dr. Lee said: 79% of the 134 patients who
underwent hormone therapy were free from biochemical failure after 5
years vs 54% of the 67 patients who had brachytherapy only (P
The researchers looked at patients who underwent hormone therapy and
received a high radiation dose, Dr. Lee said, in the belief that this
was the optimal treatment for this patient population.
For intermediate-risk patients receiving hormone therapy and
high-dose brachytherapy, there was 94% freedom from biochemical
failure after 4 years. This is a very favorable outcome that is
comparable to that of low-risk patients, she said. For
high-risk patients, there was a 77% freedom from biochemical failure
at 4 years, which suggests theres some room for improvement.
Based on this study and prior studies, Dr. Lee concluded, hormone
therapy with a high-dose radiation therapy implant is a reasonable
treatment option for intermediate-risk patients. For high-risk
patients, the groups current protocol is more aggressive, using
hormone therapy in combination with an implant and external beam