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

To compare early and late side effects in prostate cancer patients with Stage T1b-T3 disease randomized to receive 70 Gy or 78 Gy.

There were 189 patients randomized with a minimum follow-up of 2 years, that were available for this analysis. All patients were initially treated 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-field 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.

No significant differences in acute rectal or bladder toxicity were 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 were 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 analysis of the 78-Gy patients showed a significant correlation between the percentage of rectum irradiated to 70 Gy or greater and the likelihood of developing late rectal complications. Patients with more than 25% of the rectum receiving 70 Gy or greater had a 5-year risk of Grade 2 or higher complications of 37% compared to 13% for patients with 25% or less (p = 0.05). All three Grade 3 complications occurred when greater than 30% of the rectum received 70 Gy or more.

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-dimensional conformal trials.