BOSTONCombining long-term hormone therapy with radiation
therapy for locally advanced prostate cancer significantly improves
local progression, disease-free survival, freedom from distant
metastasis, and biochemical control, according to results of a phase
III clinical trial presented at the American Society for Therapeutic
Radiology and Oncology (ASTRO) annual meeting.
In this prospective study of 1,520 patients with T2c-T4 prostate
cancer, 5-year disease-free survival was 54% for those who received
long-term androgen deprivation, compared with 34% for those who were
given short-term hormone therapy (P = .0001).
While both groups had close to 80% 5-year overall survival (78% for
long-term vs 79% for short-term), only 4.2% of the long-term hormone
therapy group died of prostate cancer, compared with 7.2% of those
who received short-term hormones.
Gerald Hanks, MD, of Fox Chase Cancer Center, chair of the
multicenter trial, told ONI, For this group of patients, long-term
hormones and radiation is the standard of practice. It is the only
treatment that has been proven by prospective trials. Its the
best you can get.
Forty institutions and 100 of their affiliates contributed cases to
the trialthe largest phase III study to date of radiation
therapy for prostate cancer. Participation was so strong that the
Radiation Therapy Oncology Group (RTOG) opened the trial in June 1992
and closed it only 3 years later.
Commenting on the report of the study at the ASTRO meeting, William
Shipley, MD, of Massachusetts General Hospital, Boston, said,
The glory of this trial is, it was all done in the PSA
All patients in the study received goserelin (Zoladex) and flutamide
(Eulexin) for 2 months before and 2 months during external beam
radiation therapy (65 to 70 Gy). Afterward, they were randomized to
one of two groupsone group received no further therapy, the
other had an additional 24 months of goserelin alone. The median
follow-up was 4.8 years.
In addition to improving disease-free survival, the long-term
androgen therapy group showed better results than short-term hormone
treatment in terms of clinical local progression (6.2% vs 13%,
respectively, P = .0001), distant metastasis (11% vs 17%, P
= .001), and ASTRO-defined biochemical failure (21% vs 46%, P
The long-term group did have an increase in RTOG grade 3 and 4 bowel
complications: 42 patients, compared with 26 patients on short-term
In a subset of high-risk patients with Gleason score 8-10 tumors,
only 12 who received long-term hormone therapy died of prostate
cancer, compared with 29 in the short-term group. Their overall
survival was also better at 5 years (80% vs 70%).
Referring to two previous studies that also supported long-term
hormones for advanced prostate cancer, Dr. Hanks said he foresees no
role for short-term hormone treatments in locally advanced prostate
cancer. I think the decision is between none and
long-term, he said. These three studies have pretty much
proven the role of long-term hormones in high-risk cases, he said.
Although several retrospective studies presented at ASTRO considered
hormone therapy for less-advanced patients (see article on page 32),
Dr. Hanks reserved judgment on hormone use for low- and
intermediate-risk patients until clinical trials now underway are
Making Treatment Decisions
Despite the preponderance of evidence supporting long-term androgen
deprivation in advanced disease, some physicians still do not
prescribe it. There are lots of them, Dr. Hanks conceded.
I dont know whether its because they dont
believe the studies or they make the decision for the patient.
Androgen depletion is associated with significant side effects.
It means impotence, hot flashes, loss of energy, and
osteoporosis. Thats not a trivial package at all. Its a
big package, Dr. Hanks said.
He argued that the physician should provide full information, but the
patient should make the final decision. The patient has to
weigh interference with quality of life against a 50% decreased
chance of having prostate cancer at 5 years, he said.
As chairman of the Department of Radiation Oncology at Fox Chase, Dr.
Hanks created a Prostate Cancer Risk Assessment Program that provides
this kind of counseling as well as screening.
Some Patients Decline
Each year, one or two patients decline long-term androgen depletion,
usually because they want to preserve potency, Dr. Hanks said. Some
are younger men early in their marriages, he added. Well
treat them as well as we can. With good treatment, we can push [their
chances of 5-year disease-free survival] up to 45%, but theyre
taking short odds, he said.
Dr. Shipley noted that in the future, we may be able to
identify which men will benefit from long-term androgen deprivation,
and then well be able to spare others from the difficult side
effects of these drugs.