Clinical investigations
Prostate
Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma—long-term results of phase III RTOG 85–31

https://doi.org/10.1016/j.ijrobp.2004.08.047Get rights and content

Purpose: Radiation Therapy Oncology Group protocol 85–31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT).

Methods and Materials: Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression.

Results: Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm.

Conclusion: In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival. The improvement in survival appeared preferentially in patients with a Gleason score of 7–10.

Introduction

In the early 1980s, the Radiation Therapy Oncology Group (RTOG) began a series of studies looking at the potential usefulness of hormonal management in conjunction with definitive radiotherapy (RT) in carcinoma of the prostate. After completion of several Phase II trials, the group initiated two Phase III trials in the mid-1980s. These studies have reached maturity. The current report is a long-term update of the first large-scale Phase III trial of androgen suppression applied as an adjuvant after definitive RT.

Section snippets

Methods and materials

RTOG 85–31 was a Phase III trial designed to evaluate the effectiveness of elective (adjuvant) androgen suppression using goserelin acetate (Zoladex, Zeneca Pharmaceuticals, Wilmington, DE) on disease progression and survival in a population of patients with carcinoma of the prostate who were considered at high risk of relapse and tumor-related death.

Results

Between February 1987 and April 1992, when the study was closed, a total of 977 patients were accessioned. Of these, 488 were entered in the adjuvant arm (Arm I) and 489 in the observation arm (Arm II); 32 patients were retrospectively classified as ineligible and were excluded from the subsequent analysis, leaving 477 analyzable cases in Arm I and 468 in Arm II. The pretreatment characteristics are listed in Table 1. Figure 1 shows the absolute survival for the entire study population. At 10

Discussion

Hormonal management (androgen suppression) is a well-established modality in the treatment of patients with prostate carcinoma. Although traditionally used primarily as a palliative tool in patients with advanced disease, androgen suppression has been increasingly tested and used in a combination with surgery and RT (7, 8, 9, 10, 11, 12, 13, 14).

When considering the use of androgen suppression in conjunction with definitive RT, it is important to recognize several potential modes of interaction

Conclusion

The results of RTOG 85–31 substantiate a powerful beneficial effect of adjuvant androgen suppression. Although an improvement in all endpoints was substantiated for the entire study population, the adjuvant effect appeared preferentially in patients with a high Gleason score. This observation poses a significant practical question in the treatment of patients with a Gleason score of 2–6. Long-term adjuvant suppression with its cost and treatment-related morbidity (12, 13, 14, 15, 16, 17) may

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Supported by Public Health Services Grants CA-21661 and CA-32115 from the National Cancer Institute, National Institutes of Health, Bethesda, MD.

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