Late Urinary Toxicity Modeling After Stereotactic Body Radiation Therapy (Sbrt) In The Definitive Treatment Of Localized Prostate Cancer

Recent quality of life (QOL) analysis demonstrated that a proportion of patients treated with prostate SBRT experienced late urinary symptom flare more than 3 months after completion of treatment. The purpose of this study was to retrospectively apply normal tissue complication probability (NTCP) modeling to a cohort of men treated with prostate SBRT in an effort to derive SBRT specific bladder dosimetric predictors of late urinary flare. Two hundred sixteen men were treated definitively for localized prostate cancer using robotic radiosurgery SBRT on an 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 posterior margin and a 5 mm margin in all other directions. Patients were instructed to empty their bladder prior to simulation and treatment, and the entire bladder and its contents were contoured as a single structure. 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. QOL surveys including the American Urological Association (AUA) Symptom Index were conducted before and after treatment every 3 months for the first year and then every 6 months. Late urinary flare was defined as an AUA score > 15 with an increase ≥ 5 above baseline with subsequent return to baseline within 2 years. Phenomenologic NTCP models were fit to bladder DVHs and late urinary flare outcome data using maximum likelihood estimation. Twenty-nine patients experienced late urinary flare within 2 years of completion of prostate SBRT. Fitting of urinary bladder DVH data to a Lyman NTCP model resulted in parameter estimates of m, TD50, and n of 0.19 (-0.09 to 0.47), 38.7 Gy (31.1 to 46.4), and 0.13 (-0.14 to 0.41), respectively. Subsequent fits to threshold dose and hottest volume probit models revealed a significant association of late urinary flare with volume of bladder receiving doses greater than 36.6 Gy as well as dose to the hottest 12.7% of bladder volume. Similar results were obtained using a dose-volume cutoff model that additionally demonstrated a significant association of volume of bladder receiving at least 50% of the PD with late toxicity. The hottest volume probit model demonstrated the best fit of the data and suggests dose-volume cutoffs for D12.7% of 30 and 33.5 Gy in five fractions for a predicted complication rate of 5% and 10% at 2 years, respectively. NTCP modeling of late urinary flare after prostate SBRT demonstrates a relatively small volume effect for dose to the urinary bladder, suggesting that reduction of volume receiving elevated dose will result in decreased incidence of late urinary toxicity. Future studies will be needed to examine the impact of dose to the prostatic urethra.