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

Abstract

Significant deviations between bladder dose planned (DP) and dose accumulated (DA) 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 DP or DA as dose-volume (DV) variables. Bladder DA obtained from 150 patients were compared with DP. 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. Intermediate-high DA (V30-65 Gy and DB-ROI-20-50mm) for bladder increased compared to DP. However, at the very high dose region, DA (D0.003 cc, V75 Gy, and DB-ROI-5-10mm) were significantly lower. In MVA, single variable models were generated with odds ratio (OR)<1. DB-ROI-50mm was predictive of Grade≥1 GU toxicity for DA and DP (DA and DP; 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. Higher DA (V30-65 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.