Radiotherapy and androgen ablation for clinically localized high-risk prostate cancer

Abstract

Purpose : The response of patients with clinical stages T1–4 prostate cancer to radiotherapy is variable. A particularly poor prognostic group has been found to be comprised of those with pretreatment prostate specific antigen (PSA) levels above 30 ng/ml with any tumor grade, or PSA levels > 10 and ≤ 30 with tumors grade 3 or 4. These patients have over an 80% actuarial risk of biochemical failure 3 years after definitive external beam radiotherapy. Thus, patients with these high-risk features require more aggressive therapy. During the last 3–4 years, the policy to treat such patients with radiotherapy and androgen ablation (XRT/HORM) was instituted. A retrospective comparison was made between high-risk patients treated with radiotherapy alone (XRT) vs. XRT/HORM. Methods and Materials : Between 1987 and 1991, there were 81 high-risk patients treated with XRT. There were 38 high-risk patients treated with XRT/HORM between 1990 and 1992. The median follow-up was 37 months for the XRT group and 22 months for the XRT/HORM group. No patient had clinical, radio-graphic, or pathologic evidence of lymph node involvement. The median dose to the prostate was 66 Gy for the XRT group and 68 Gy for the XRT/HORM group. Results : The distributions of several potential prognostic factors were analyzed. Significant differences between the groups were observed for tumor grade, pretreatment prostatic acid phosphatase, and age. The XRT/HORM group was composed of patients with worse features, including a greater proportion of patients with grade 4 tumors, more with abnormal acid phosphatase levels, and more under 60 years of age. The actuarial incidence of a rising PSA at 3 years for the XRT group was 81% vs. 15% for the XRT/HORM group ( p < 0.0001). In addition, local relapse at 3 years was 34% for the XRT group and 15% for the XRT/HORM group ( p < 0.02). There was no difference between the groups in terms of survival. Cox proportional hazards analyses were performed using several disease end points, including a rising PSA, a rising PSA or disease relapse, any disease relapse, and local relapse, and the only prognostic factor of independent predictive value was treatment group, i.e., XRT vs. XRT/HORM. Conclusions : Based on biochemical and disease relapse end points, definitive radiotherapy is insufficient treatment for high-risk prostate cancer patients. The addition of androgen ablation significantly reduces the recurrence rates, although longer follow-up is needed to determine if the combined treatment impacts significantly on survival.