Predictors for late genitourinary toxicity in men receiving radiotherapy for high-risk prostate cancer using planned and accumulated dose

Background and purpose: Significant deviations between bladder dose planned (D_P) and dose accumulated (D_A) have been reported in patients receiving radiotherapy for prostate cancer. This study aimed to construct multivariate analysis (MVA) models to predict the risk of late genitourinary (GU) toxicity with clinical and D_P or D_A as dose-volume (DV) variables.

Materials and methods: Bladder D_A obtained from 150 patients were compared with D_P. MVA models were built from significant clinical and DV variables (p < 0.05) at univariate analysis. Previously developed dose-based-region-of-interest (DB-ROI) metrics using expanded ring structures from the prostate were included. Goodness-of-fit test and calibration plots were generated to determine model performance. Internal validation was accomplished using Bootstrapping.

Results: Intermediate-high D_A (V_{30-65 Gy} and DB-ROI-20-50 mm) for bladder increased compared to D_P. However, at the very high dose region, D_A (D_{0.003 cc}, V_{75 Gy,} and DB-ROI-5-10 mm) were significantly lower. In MVA, single variable models were generated with odds ratio (OR) < 1. DB-ROI-50 mm was predictive of Grade ≥ 1 GU toxicity for D_A and D_P (D_A and D_P; OR: 0.96, p: 0.04) and achieved an area under the receiver operating curve (AUC) of > 0.6. Prostate volume (OR: 0.87, p: 0.01) was significant in predicting Grade 2 GU toxicity with a high AUC of 0.81.

Conclusions: Higher D_A (V_{30-65 Gy}) received by the bladder were not translated to higher late GU toxicity. DB-ROIs demonstrated higher predictive power than standard DV metrics in associating Grade ≥ 1 toxicity. Smaller prostate volumes have a minor protective effect on late Grade 2 GU toxicity.