External beam radiotherapy dose response of prostate cancer

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

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.

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.

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.