Complications from radiotherapy dose escalation in prostate cancer: Preliminary results of a randomized trial

Objective: To compare early and late side effects in prostate cancer patien ts with Stage T1b-T3 disease randomized to receive 70 Gy or 78 Gy. Methods: There were 189 patients randomized with a minimum follow-up of 2 y ears, that were available for this analysis. All patients were initially tr eated with a 4-field box to an isocenter dose of 46 Gy at 2 Gy per fraction . In the 70-Gy arm, treatment was continued to a reduced volume using a 4-f ield box technique. In the 78-Gy arm, treatment was continued to a reduced volume using a conformal 6-field arrangement. Side effects were graded on a 1-4 scale, adapted from Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. Results: No significant differences in acute rectal or bladder toxicity wer e seen between the two treatment techniques (p > 0.6 for all comparisons). The 5-year Kaplan-Meier risks of Grade 2 or higher late bladder toxicity we re 20% and 9% for 70-Gy and 78-Gy groups, respectively (log rank, p = 0.8). The 5-year risks of Grade 2 or higher late rectal toxicity were 14% and 21 % for 70 Gy and 78 Gy, respectively (p = 0.4). Dose-volume histogram analys is of the 78-Gy patients showed a significant correlation between the perce ntage of rectum irradiated to 70 Gy or greater and the likelihood of develo ping late rectal complications. Patients with more than 25% of the rectum r eceiving 70 Gy or greater had a 5-year risk of Grade 2 or higher complicati ons of 37% compared to 13% for patients with 25% or less (p = 0.05). All th ree Grade 3 complications occurred when greater than 30% of the rectum rece ived 70 Gy or more. Conclusion: The overall rate of complications was similar in both treatment arms. However, there is evidence for a significant increase in late rectal complications when more than 25% of the rectum received 70 Gy or greater. This parameter may serve as a benchmark for the design of future three-dime nsional conformal trials. (C) 2000 Elsevier Science Inc.