External beam radiotherapy dose response of prostate cancer

Abstract

Purpose: To determine the external beam radiotherapy dose response of palpable Stage T1-T4, mostly Nx, patients with adenocarcinoma of the prostate.

Methods and materials: There were 938 men consecutively treated between 1987 and 1995 who had pretreatment prostate specific antigen (PSA) levels. Posttreatment failure was defined as disease recurrence and/or two elevations in PSA on consecutive follow-up visits. The radiotherapy technique consisted of a four-field box with a small four-field reduction after 46 Gy in 844 patients (total dose of 60-70 Gy) or with a six-field conformal boost after 46 Gy in 94 patients (total dose of 74-78 Gy). Neoadjuvant or adjuvant androgen ablation was not used in any patient. Median follow-up was 40 months.

Results: The mean and median radiotherapy doses for the entire group were 67.8 +/- 13.3 Gy (+/-SEM) and 66 Gy. The mean radiotherapy dose was higher in those who had Stage T3/T4 disease, Gleason scores of 8-10, or pretreatment PSAs of > 4 ng/ml. In general, patients with more aggressive pretreatment prognostic features were treated to higher doses; yet, those that relapsed or had a rising PSA were treated to significantly lower doses. Actuarial analyses were facilitated by dividing patients into three dose groups: < or = 67, > 67-77, and > 77 Gy. The actuarial freedom from failure rates at 3 years were 61, 74, and 96% for the low, intermediate, and high dose groups. Stratification of the patients by pretreatment PSA revealed that dose was a significant correlate of freedom from relapse or a rising PSA for those with PSAs > 4-10, > 10-20, and > 20 ng/ml. The only patients in which an improvement in outcome was not related to higher doses were those with a pretreatment PSA < or = 4 ng/ml. Dose was significantly associated with freedom from failure for Stage T1/T2 and Stage T3/T4 patients, as well as for those stratified by Gleason score. Multivariate analysis using Cox proportional hazards models showed that dose was an independent and highly significant predictor of relapse or a rising PSA.

Conclusion: This retrospective review strongly indicates that radiotherapy dose to the prostate is critical to the cure of prostate cancer, even for favorable patients with pretreatment PSAs of > 4-10 ng/ml, Stages T1/T2, or Gleason scores of 2-6. Final confirmation awaits the results of our randomized trial.