Dosimetric Clues to Addressing Urinary Toxicity Following Stereotactic Prostate Radiation Therapy

Delayed genitourinary (GU) toxicity is reported following definitive stereotactic body radiation therapy (SBRT) for prostate cancer in 15% to 30% of patients. The purpose of this study is to investigate whether there is a relationship between radiation dose to the bladder and urethra and GU toxicity grade ≥ 2 (National Cancer Institute Common Terminology Criteria for Adverse Events 4.0) in patients treated with SBRT.

PROstate Multicenter External beam radioTHErapy Using Stereotactic boost was a phase 2 multicenter trial exploring an SBRT boost of 19 to 20 Gy in 2 fractions to the prostate combined with fractionated external beam radiation therapy as a virtual high-dose-rate brachytherapy boost for patients with prostate cancer. Several bladder and urethral constraints were mandated prospectively. Bladder and the urethral planning organ at risk volume (PRV) dosimetry was correlated with physician-reported GU toxicity for patients ≥ 6 months following SBRT. An association between prior transurethral resection of the prostate (TURP) and urinary toxicity was also examined. Univariant and multivariate analyses were performed.

Of the 151 patients, 87 had complete dosimetric data, and these patients were included in this analysis. In this cohort, 19.5% experienced grade ≥ 2 GU toxicity more than 6 months after stereotactic radiation therapy. On univariate analysis, prostatic urethral length, urethral PRV volume, bladder D2 cc, D5 cc, D10 cc, D15 cc, and bladder V8 were predictive of GU toxicity (all P < .05). In the 14 patients who had prior TURP, 6 (43%) experienced GU toxicity compared with 15% for those without prior TURP (P = .015). Multivariate analysis showed that prostatic urethral length, urethral PRV volume, bladder 10 cc, and bladder 15 cc remained statistically significant factors predicting GU toxicity.

Prostate SBRT delivered as a virtual high-dose-rate boost is well tolerated overall. However, delayed GU toxicity is experienced by a significant minority of patients. Additional bladder constraints including D10 cc < 17 Gy and D15 cc < 15 Gy may further reduce the risk of delayed GU toxicity. Prior TURP may be a plausible additional risk factor.