Evolution of toxicity after conformal radiotherapy for prostate cancer

The limiting factor for radiation (RT) dose-escalation is normal tissue toxicity. In dose-escalation studies, it is important to determine the factors associated with toxicity and the length of follow-up period after which a particular RT dose is considered safe. We analyzed 449 prostate cancer patients treated with RT at our institution and followed for a median of 27 months. Genitourinary (GU) and gastrointerological (GI) complications were graded and analyzed using three different statistical models. Univariate and multivariate analyses were conducted for factors associated with toxicity. There was no RTOG grade 4 or 5 toxicity. Only 23 patients (5%) experienced grade 3 toxicity. After treatment, there was an initial rapid decline in the risk of toxicity following treatment, followed by an increase or stabilization of the toxicity with time of follow-up. The breakpoints between the two periods were 2 y (any toxicity) and 1 y (high toxicity) for GU and 9 months (any toxicity, high toxicity) for GI. Age, dose, fraction size, duration of treatment and hospital of treatment emerge as important factors in the probability of developing toxicity. Our study shows that delivering conventional doses using conformal techniques is associated with minimal high-grade toxicity. However, even within a narrow dose range and fraction size used, differences do emerge which should lead one to be cautious in extending the results of dose escalation study to the community practice without a sufficient follow-up.