(S013) Heterogeneity Within the Prostate and Risk-Adapting Dose-Volume Analysis With SBRT for Prostate Cancer

Zachary A. Seymour, MD, Li Zhang, PhD, Albert J. Chang, MD, I-Chow J. Hsu, MD, Alexander R. Gottschalk, MD, PhD; Department of Radiation Oncology, Cancer Center, University of California, San Francisco

PURPOSE AND OBJECTIVES: To evaluate dose-volume relationships of genitourinary (GU) toxicity after stereotactic body radiotherapy (SBRT) for prostate cancer to determine optimal cut points for dosimetric parameters based on prostatic volume.

MATERIALS AND METHODS: Fifty-one of 56 patients treated with SBRT for prostate cancer had evaluable dose-volume histograms. All patients were treated in a uniform manner, receiving a total dose of 38 Gy in 4 fractions. Acute, late, and overall GU toxicities were documented according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE v4). Dose volumes were assessed via receiver operating characteristic (ROC) curves to determine optimal cut points at 0.5-Gy dose-volume intervals, and probabilities of toxicity for each cut point were produced. Only dose volumes with a sensitivity and specificity > 0.65 were considered for analysis of GU grade 2+ toxicity.

RESULTS: The median age at treatment was 68 years, and median prostate volume was 45.4 mL. The median prescription isodose line was 68%. The median clinical follow-up was 35.49 months. Acute and late grade 2+ GU toxicities occurred in 35.7% and 23.2%, respectively, with only 2 grade 3 GU toxicities. Overall toxicity was associated with baseline prostate volume (continuous, P = .006; hazard ratio [HR] = 1.06; 95% confidence interval [CI], 1.02–1.10) with an overall risk of 39% for grade 2+ toxicity in patients with prostate volumes > 45 mL (AUC 0.722, sensitivity 67%, specificity 71%). The probability of late grade 2+ GU toxicity was associated with absolute and normalized prostate volumes across doses from 46–50 Gy, suggestive of increasing late toxicity with intraprostatic heterogeneity. Normalized V50 Gy of 9% was the strongest normalized prostate volume associated with a 19% late grade 2+ GU toxicity rate (AUC 0.763, sensitivity 82%, specificity 68%). Urethra 42 Gy volume was also associated with grade 2+ toxicity with an optimal cutoff of 2.1 mL (AUC 0.62, sensitivity 82%, specificity 70%, probability 19%). No bladder volume cut points were strongly associated with late or overall GU grade 2+ toxicity.

CONCLUSIONS: Greater intraprostatic heterogeneity was associated with late grade 2+ GU toxicity. Given the high correlation of prostate volume with toxicity, SBRT dose parameters should be individualized and risk-adapted based on normalized prostate volumes, including a V50 not to exceed 9% of the prostate. The urethra is an important organ at risk, and the 42-Gy dose-volume should be limited to 2 mL, while bladder dose-volumes appear to be poor predictors of GU grade 2+ toxicity.

Proceedings of the 97th Annual Meeting of the American Radium Society - americanradiumsociety.org