ESTRO 2025 - Abstract Book

S2135

Clinical - Urology

ESTRO 2025

Purpose/Objective: This study aims to evaluate the relationship between dose metrics for the urethra and bladder and the occurrence of grade 2 or higher genitourinary (GU2+) toxicities in patients undergoing moderate hypofractionated radiotherapy (MHRT) with mpMRI- and PSMA-PET/CT-based focal dose escalation for localized prostate cancer. The goal is to identify significant dosimetric predictors of genitourinary (GU) toxicities and provide insights for improving treatment safety. Material/Methods: The HypoFocal phase II trial (DRKS00017570, ARO2020-01) is a prospective, non-randomized, bicentric study investigating focal dose escalation based on mpMRI- and PSMA-PET in MHRT (60.0 Gy in 20 fractions, boost up to 75.0 Gy) and HDR-BT in patients with intermediate- and high-risk localized primary prostate cancer [1]. In this analysis we included 23 patients with at least 24 months of follow-up treated with focal dose escalated MHRT. We retrospectively delineated the urethra, including the intraprostatic and membranous parts, using co-registered T2 weighted MRIs following established contouring guidelines [2]. The bladder was also delineated for inclusion in the analysis. GU toxicities were classified using CTCAE v5.0 criteria. Dose matrices were exported and converted to EQD2 using α/β ratios of 5.0 Gy for the urethra [3] and 0.6 Gy for the bladder [4]. The generalized EQD2 (gEUD2Gy) with an alpha-volume-effect parameter of 3.3 was calculated for the urethra and its sub-regions [3]. A multivariate logistic regression model was fitted to analyze the correlation of GU2+ toxicities with D0.1cc for the urethra and D2cc for the bladder. Results: Grade 2+ GU toxicity was observed in 6 out of 23 patients. Mean and standard deviation EQD2 doses for the urethra and bladder were calculated for the GU2+ and control groups (Figure 1). Logistic regression analysis showed no significant correlation between GU2+ outcomes and D0.1cc for the urethra ( p=0.554 ) or D2cc for the bladder ( p=0.267 ). Similarly, gEUD2Gy distributions for the urethra and its sub-regions showed no significant differences between groups. Conclusion: Within the HypoFocal phase II trial, we found no clear relationship between urethral dose and grade 2+ GU toxicity. Further follow-up and a larger patient cohort from the ongoing HypoFocal-SBRT trial (DRKS00022915) may provide additional evidence on the optimal dose constraints for urethra and bladder substructures in hypofractionated treatment regimes. Identifying the most sensitive regions of the urethra and optimizing dose distribution strategies, possibly through urethral sparing techniques, are essential for improving GU toxicity outcomes. References: [1] Zamboglou C, et al. PSMA-PET- and MRI-Based Focal Dose Escalated Radiation Therapy of Primary Prostate Cancer [...] Int J Radiat Oncol Biol Phys . 2022; doi:10.1016/j.ijrobp.2022.04.020 [2] Le Guévelou J, et al. Urinary Organs at Risk for Prostate Cancer External Beam Radiation Therapy [...] Pract Radiat Oncol . 2024;14(6):541-554. doi:10.1016/j.prro.2024.05.009 [3] Panettieri V, et al. (2020) External Validation of a Predictive Model of Urethral Strictures for Prostate Patients Treated With HDR Brachytherapy Boost. Front. Oncol. 10:910. doi: 10.3389/fonc.2020.00910 [4] Brand DH, et al. The Fraction Size Sensitivity of Late Genitourinary Toxicity [...] Int J Radiat Oncol Biol Phys . 2023;115(2):327-336. doi:10.1016/j.ijrobp.2022.08.030 Keywords: genitourinary toxicity, prostate cancer, MHRT