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(Drug information on goserelin) (Zoladex), 3.6 mg monthly for 4 months, plus flutamide(Drug information on 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.