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Clinical Trial
. 2022 Feb:167:127-132.
doi: 10.1016/j.radonc.2021.12.027. Epub 2021 Dec 28.

Urethral and bladder dose-effect relations for late genitourinary toxicity following external beam radiotherapy for prostate cancer in the FLAME trial

Veerle H Groen  1 , Marcel van Schie  2 , Nicolaas P A Zuithoff  3 , Evelyn M Monninkhof  3 , Martina Kunze-Busch  4 , Johannes C J de Boer  1 , Jochem van der Voort van Zijp  1 , Floris J Pos  2 , Robert Jan Smeenk  4 , Karin Haustermans  5 , Sofie Isebaert  5 , Cédric Draulans  5 , Tom Depuydt  5 , Helena M Verkooijen  6 , Uulke A van der Heide  2 , Linda G W Kerkmeijer  7
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Free article
Clinical Trial

Urethral and bladder dose-effect relations for late genitourinary toxicity following external beam radiotherapy for prostate cancer in the FLAME trial

Veerle H Groen et al. Radiother Oncol. 2022 Feb.
Free article

Abstract

Purpose or objectives: The FLAME trial (NCT01168479) showed that by adding a focal boost to conventional fractionated EBRT in the treatment of localized prostate cancer, the five-year biochemical disease-free survival increased, without significantly increasing toxicity. The aim of the present study was to investigate the association between radiation dose to the bladder and urethra and genitourinary (GU) toxicity grade ≥2 in the entire cohort.

Material and methods: The dose-effect relations of the urethra and bladder dose, separately, and GU toxicity grade ≥2 (CTCAE 3.0) up to five years after treatment were assessed. A mixed model analysis for repeated measurements was used, adjusting for age, diabetes mellitus, T-stage, baseline GU toxicity grade ≥1 and institute. Additionally, the association between the dose and separate GU toxicity subdomains were investigated.

Results: Dose-effect relations were observed for the dose (Gy) to the bladder D2 cm3 and urethra D0.1 cm3, with adjusted odds ratios of 1.14 (95% CI 1.12-1.16, p < 0.0001) and 1.12 (95% CI 1.11-1.14, p < 0.0001), respectively. Additionally, associations between the dose to the urethra and bladder and the subdomains urinary frequency, urinary retention and urinary incontinence were observed.

Conclusion: Further increasing the dose to the bladder and urethra will result in a significant increase in GU toxicity following EBRT. Focal boost treatment plans should incorporate a urethral dose-constraint. Further treatment optimization to increase the focal boost dose without increasing the dose to the urethra and other organs at risk should be a focus for future research, as we have shown that a focal boost is beneficial in the treatment of prostate cancer.

Keywords: Bladder dose; Dose-effect relations; External beam radiotherapy; Focal boosting; Genitourinary toxicity; Prostate cancer; Urethral dose.

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Conflict of interest statement

Conflict of interest statement All authors declare having no conflict of interest related to the content of this manuscript.

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