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

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical and Translational Radiation Oncology Pub Date : 2025-01-10 DOI:10.1016/j.ctro.2025.100918

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

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Abstract

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 (D_U0.1cc) 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, D_U0.1cc 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 D_U0.1 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.