Predictors of Acute Urinary Flare Following Stereotactic Body Radiation Therapy (SBRT) in the Definitive Treatment of Localized Prostate Cancer

Abstract

Clinical studies have demonstrated an association between genitourinary toxicity and dose to critical genitourinary structures in patients treated with brachytherapy and external beam radiation therapy (EBRT) for prostate cancer. The purpose of this study was to identify patient related and dosimetric predictors of acute urinary flare in a prospective cohort of patients undergoing stereotactic body radiation therapy (SBRT) for localized prostate cancer. One hundred three men were treated definitively for localized prostate cancer using robotic SBRT on a prospective institutional protocol. The planning target volume (PTV) consisted of the prostate and proximal seminal vesicles as defined on non-contrast CT and fused T2 MRI with a 3 mm margin at the prostate-bladder interface. Inverse plans were generated with a prescription dose (PD) of 35 to 36.25 Gy in 5 fractions to the PTV using 6 MV photons. Patients who were not already using alpha-receptor antagonists were prophylactically treated with tamsulosin. Patient surveys including the International Prostate Symptom Score (IPSS) were conducted before and one week following the completion of SBRT. Cumulative and differential dose-volume histograms (DVHs) were created for the bladder, bladder wall, bladder neck, and prostatic urethra. Acute urinary flare was defined as an increase in IPSS of 5 points or more with an absolute score of at least 15 points. Twenty-one point four percent of patients experienced acute urinary flare one week following completion of prostate SBRT. Dose-volume cut-off analysis was performed in order to identify statistically significant predictors of acute urinary flare. Univariate regression analysis of patient-related and dosimetric parameters demonstrated that prostatic volume and bladder wall D15.5% were significant predictors of acute urinary flare. Multivariate regression analysis confirmed both prostatic volume and bladder wall D15.5% as significant independent predictors of urinary flare, with a median split prostate volume of 36 cm3 resulting in an 11.8% versus 37.2% incidence of acute flare and a median split dose to the hottest 15.5% of bladder wall of 32.6 Gy resulting in a 9.8% versus 34.6% incidence of acute flare. No dosimetric parameters of the bladder, bladder neck, or prostatic urethra were significantly associated with increased toxicity. Dose-volume histogram analysis of acute urinary toxicity identified that the bladder wall D15.5%, in addition to prostate volume, is a significant predictor of acute urinary flare in patients treated with SBRT for prostate cancer. The consequential effects of acute urinary flare in this prospective cohort of patients treated with prostate SBRT in terms of late urinary toxicity warrants further investigation.