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-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).