Voxel-Based Analysis for Identification of Urethrovesical Subregions Predicting Urinary Toxicity After Prostate Cancer Radiation Therapy

Abstract

To apply a voxel-based analysis to identify urethrovesical symptom-related subregions (SRSs) associated with acute and late urinary toxicity in prostate cancer radiation therapy. Two hundred seventy-two patients with prostate cancer treated with intensity-modulated radiation therapy/image-guided radiation therapy were analyzed prospectively. Each patient's computed tomography imaging was spatially normalized to a common coordinate system via nonrigid registration. The obtained deformation fields were used to map the dose of each patient to the common coordinate system. A voxel-based statistical analysis was applied to generate 3-dimensional dose-volume maps for different urinary symptoms, allowing the identification of corresponding SRSs with statistically significant dose differences between patients with or without toxicity. Each SRS was propagated back to each individual's native space, and dose-volume histograms (DVHs) for the SRSs and the whole bladder were computed. Logistic and Cox regression were used to estimate the SRS's prediction capability compared with the whole bladder. A local dose-effect relationship was found in the bladder and the urethra. SRSs were identified for 5 symptoms: acute incontinence in the urethra, acute retention in the bladder trigone, late retention and dysuria in the posterior part of the bladder, and late hematuria in the superior part of the bladder, with significant dose differences between patients with and without toxicity, ranging from 1.2 to 9.3Gy. The doses to the SRSs were significantly predictive of toxicity, with maximum areas under the receiver operating characteristic curve of 0.73 for acute incontinence, 0.62 for acute retention, 0.70 for late retention, 0.81 for late dysuria, and 0.67 for late hematuria. The bladder DVH was predictive only for late retention, dysuria, and hematuria (area under the curve, 0.65-0.72). The dose delivered to the urethra and the posterior and superior parts of the bladder was predictive of acute incontinence and retention and of late retention, dysuria, and hematuria. The dose to the whole bladder was moderately predictive.