BOSTONRaising 3D conformal radiation therapy doses for
localized prostate cancer produced far less toxicity than expected in a
nine-center cooperative study reported at the annual meeting of the American
Society for Therapeutic Radiology and Oncology (ASTRO).
Jeff M. Michalski, MD, of Washington University School of
Medicine, St. Louis, said that acute toxicity was "remarkably low"
and late toxicity also was low, compared to historical data from trials
conducted in the 1970s. "Despite higher radiation doses, the tolerance is
significantly better than in older trials with older techniques," he told
He noted that the reference doses were nearly 1,000 cGy higher
in the phase I/II trial (RTOG 9406) than in the two earlier studies (RTOG 7506
and RTOG 7706). The patients tolerated the first dose level tested, 68.4 Gy, so
well, he said, that the investigators received permission to test at a second
level, 73.8 Gy. This also resulted in a dramatically lower rate of observed
complications than expected.
From 1994 to 1999, 424 patients with localized prostate cancer
were entered into the trial. All were nonmetastastic with PSAs less than 70
Initially, patients receiving neoadju-vant hormonal therapy
were excluded, Dr. Michalski said, but patients receiving neoadjuvant hormonal
therapy for 3 to 6 months were accepted after its use was supported in other
trials. Patients whose prognosis was so favorable that dose escalation would be
inappropriate were excluded. The patients were separated into three groups:
Group 1 had T1-2 tumors with a seminal vesicle invasion
(SVI) risk of less than 15%. Patients received the minimum doses of 68.4 Gy or
73.8 Gy to the planning target volume, including a margin of 5 to 10 mm around
Group 2 had the same tumor staging with SVI risk at or
greater than 15%. Patients in this group received 3D conformal radiation
therapy to the prostate and seminal vesicle plus an initial planning target
volume margin to a dose of 55.8 Gy. This was followed by a reduction in
treatment volume to the prostate plus a second planning target volume margin to
68.4 Gy or 73.8 Gy.
Group 3 patients had T3 tumors. The prostate and seminal
vesicle and planning treatment volume margin was treated to 68.4 Gy or 73.8 Gy
with no reduction in treatment volume.
Acute toxicity was very low, with grade 3 toxicity less than 1%
for group 1, less than 3% for group 2, and less than 10% for group 3. The
highest incidence occurred in group 3 patients treated to 73.8 Gy (7% grade 3
and 3% grade 4).
Late toxicity was low compared to the historical trials. Only
two patients had grade 3 bladder toxicity, and no other late grade 3 toxicities
were reported. Grade 2 toxicities ranged from 16% to 21% in groups 1 and 2, and
from 25% to 31% in group 3.
Patients with higher-stage disease had a higher rate of bladder
and rectal complications. Dr. Michalski said this was probably because larger
volumes of the bladder and rectum were treated. Patients who received
neoadjuvant hormonal therapy also had a higher rate of complications, he said,
speculating that this might be due to the difficulty of "planning
radiation on a shrinking target." This finding will need to be confirmed
with more follow-up, he added.
The study is ongoing, and the investigators will do dose-volume
analysis of the bladder and rectum to predict the risk of grade 2 and greater
acute and late toxicities. "We plan to establish maximum tolerated vs
standard dose," Dr. Michalski said.