3344 - Novel Insights into Urethral Sphincter Complex Dosimetry and GU Toxicity of MR-Guided Stereotactic Body Radiotherapy (MRgSBRT) in Localized Prostate Cancer:Single-Institution Study

Purpose/Objective(s): Despite significant advancements in radiotherapy techniques and sophisticated dosimetric planning techniques, genitourinary (GU) toxicity remains an unresolved challenge for prostate cancer (PCa) patients. This study hypothesized that the utilization of SBRT doses (?6 Gy/fraction) in PCa treatment may confer greater radiation damage to late-responding, low a/ß tissues with higher sensitivity to fraction sizes , namely the urethral sphincter complex (USC) and may be associated with GU toxicity. The objective was to determine if there was any dosimetric association with USC by analyzing the dosimetric parameters of structures, including proximal lissosphincter muscle (PLSM) and distal rhabdosphincter muscle (DRSM) with ?G2 CTCAE v5.0 GU toxicities in patients with localized PCa after MRgSBRT. Furthermore, quantitative assessment was made to investigate the large fractional dose effect on morphological alterations, including thickness, length, spherical diameter, and total volume of USC.

Materials/Methods: This retrospective study included 105 PCa patients treated with MRgSBRT (36.25Gy in 5 fractions ± DIL boost) in a single institution. Urethral sphincter substructures, including DRSM and PLSM were delineated on T2-weighted MRI. Dosimetric parameters were retrieved for each structure, including mean dose, maximal dose, absolute dose and relative volume dose metrics. All morphological data were assessed at baseline and last-day treatment, including total volume (cc), spherical diameter (mm), length (mm), anterior-posterior thickness (mm), lateral thickness (mm) and mean T2 signal intensity (SI). Principal component analysis (PCA)-based multivariable logistic regression was applied to establish association of individual structural dose with GU toxicity. Paired t-test and/or Wilcoxon signed rank test were adopted to determine if significant morphological changes occurred between baseline and last treatment of MRgSBRT.

Results: The incidence of ?G2 GU toxicity was 15.2%. PCA-based analysis identified mean dose to DRSM as a significant predictor of ?G2 GU toxicities (OR=2.23, 95% CI:1.29-4.04, p=0.004), with an optimal threshold of 37.5Gy (AUC=0.77). Morphological analysis revealed significant reduction in DRSM volume ( -26.2%, p<0.01), length (-20%, p<0.01) and thickness (AP: -17.3%; Lateral: -16.8%, p<0.01). A significant reduction in mean T2 SI was observed in the DRSM (µT2 SI:-3740; p<0.01), which may reflect early fibrotic changes.

Conclusion: DRSM dosimetry and morphology are critical factors influencing toxicity in MRgSBRT. These findings support more personalized radiotherapy strategies to reduce toxicity and enhance long term QOL for PCa treatment. Further study should be implemented to confirm the correlation of DRSM and GU morbidities.