Associations of dose to the urethra and long-term patient-reported outcomes after radiotherapy with EBRT and HDR brachytherapy boost for prostate cancer

Purpose: Implications of radiation dose exposure to the urethra on urinary morbidity after prostate radiotherapy are poorly understood, especially by long-term patient-reported outcomes (PRO). Therefore, our primary objective was to investigate associations of urethral dose and long-term patient-rep...

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Main Authors: Lars Haack, David Krug, Justus Domschikowski, Olaf Wittenstein, Severin Rodler, Philipp Nuhn, Christof van der Horst, Claudia Schmalz, Christian Schulz, Oliver Blanck, Frank-André Siebert, Alexander Fabian
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Clinical and Translational Radiation Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405630825000084
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Summary:Purpose: Implications of radiation dose exposure to the urethra on urinary morbidity after prostate radiotherapy are poorly understood, especially by long-term patient-reported outcomes (PRO). Therefore, our primary objective was to investigate associations of urethral dose and long-term patient-reported urinary morbidity after external beam radiotherapy and high-dose rate brachytherapy boost for prostate cancer. Materials and methods: We conducted a pre-registered (https://doi.org/10.17605/OSF.IO/A6DC3) cross-sectional study at a tertiary academic center including a consecutive sample of patients being at least two years after treatment. Primary outcome measurements included urinary domains of the EPIC-26 questionnaire. Their associations with predefined urethral dose levels were assessed by univariable analyses (Pearson’s correlation) and by predefined multivariable analyses (multiple regression). Sample size calculation was based on a predefined multivariable model. A p-value < 0.05 was considered statistically significant. Results: Among 277 screened patients, 113 patients were alive, eligible, consented, and provided PRO. The median time passed since radiotherapy was 4 years. Per univariable analysis, a higher near maximum point dose of the urethra (DU0.1cc) was associated with worse urinary incontinence (r = -0.32; CI = −0.48 − -0.13; p < 0.001) and worse overall urinary function (r = -0.21; CI = −0.38 − -0.03; p = 0.02) of the respective EPIC-26 domains. Per predefined multivariable analysis, DU0.1cc and urinary incontinence remained significantly associated (B = −0.005; CI = −0.008 − -0.002; p = 0.003). These associations were only present, when very high DU0.1 cc above 137 Gy were kept in the analysis. Conclusions: Very high urethral near point doses appear to be associated with worse long-term patient-reported urinary morbidity after radiotherapy for prostate cancer. Urethral dose should be considered in practice and future trials to potentially minimize long-term urinary morbidity. Trial registration: The study protocol was pre-registered prior to patient accrual on the Open Science Framework (https://doi.org/10.17605/OSF.IO/A6DC3).
ISSN:2405-6308