PHOENIXUpdated results from RTOG 86-10 show a continuing trend
for improved overall survival among patients with locally advanced
prostate cancer who received androgen ablation in addition to
radiation therapy, compared with those receiving radiation therapy
alone, Miljenko V. Pilepich, MD, reported at the annual meeting of
the American Society for Therapeutic Radiology and Oncology (ASTRO).
At 5 years, the survival curves overlap and then start to
diverge. The P value at 8 years is .11, and the difference is about
10%, so it would appear that, with time, the figures will become
significant statistically, said Dr. Pilepich, of St. Joseph
Mercy Hospital, Ann Arbor, Michigan.
This phase III trial tested the hypothesis that androgen ablation
before and during radiation therapy may enhance local control and
eventually improve survival by diminishing the tumor bulk and by, in
some favorable fashion, interacting on a cellular level with
radiation, he said.
Eligible patients had bulky primary lesions (T2-T4) with or without
pelvic lymph node involvement and without evidence of distant
metastases. Patients were randomized to receive standard radiotherapy
alone or with adjuvant androgen ablation consisting of goserelin
(Zoladex), 3.6 mg monthly for 4 months, plus flutamide (Eulexin), 250
mg three times a day.
Of 471 patients enrolled, 456 were evaluable. Please note that
close to 40% of the patients had elevated acid phosphatase,
indicating the advanced nature of disease in this population,
Dr. Pilepich pointed out. Median follow-up as of October 1998 was 6.5
years for all patients and 7.5 years for patients still alive.
The addition of androgen ablation significantly reduced the incidence
of local failure, he said. At 5 years, 22% of the combination
patients had a local recurrence vs 35% of those receiving
radiotherapy alone. At 8 years, the corresponding numbers were 31%
and 43%. Its worth noting that the curves remain
separate, and there is no tendency to converge, he said.
The incidence of distant metastases was also significantly reduced in
the combination arm, with a 10% difference at 8 years (35% vs 45%).
The improvement in progression-free survival is also highly
significant31% vs 21% at 8 years (P = .002).
So far, it would appear that androgen ablation has produced a
very beneficial effect on all endpoints, Dr. Pilepich said.
However, the question remains whether this treatment is
applicable to all patients.
Subset analysis showed that patients with a Gleason score of 2 to 7
had a significantly reduced incidence of local failure (16%) with
combination therapy, whereas patients with a Gleason score of 8 to 10
showed no benefit. The incidence of distant metastases was also not
significantly different in the high Gleason score groups, he said,
and disease-free survival, although quite strikingly
improved in the low Gleason population with combination therapy,
is barely different in the high Gleason population.
For overall survival, the difference in the low Gleason group has
almost reached significance (P = .09), Dr. Pilepich said, but
in the high Gleason population, the difference is not there at all.
He noted that in a parallel study in which androgen ablation was used
long term, a remarkable improvement in outcome, including survival,
was observed in the same population (Gleason 8 to 10).
Dr. Pilepich concludes that for patients with Gleason score of 2 to
7, four months of androgen ablation, as used in this trial, is
adequate and beneficial, but that hormonal management should be
applied for a much longer period in patients with high Gleason scores.