TY - JOUR
T1 - Urethral and bladder dose-effect relations for late genitourinary toxicity following external beam radiotherapy for prostate cancer in the FLAME trial
AU - Groen, Veerle H
AU - van Schie, Marcel
AU - Zuithoff, Nicolaas P A
AU - Monninkhof, Evelyn M
AU - Kunze-Busch, Martina
AU - de Boer, Johannes C J
AU - van der Voort van Zijp, Jochem
AU - Pos, Floris J
AU - Smeenk, Robert Jan
AU - Haustermans, Karin
AU - Isebaert, Sofie
AU - Draulans, Cédric
AU - Depuydt, Tom
AU - Verkooijen, Helena M
AU - van der Heide, Uulke A
AU - Kerkmeijer, Linda G W
N1 - Funding Information:
This study is supported by the Dutch Cancer Society (KWF, project 10088).
Publisher Copyright:
© 2021 The Author(s)
PY - 2022/2
Y1 - 2022/2
N2 - 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 cm
3 and urethra D0.1 cm
3, 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.
AB - 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 cm
3 and urethra D0.1 cm
3, 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.
KW - Bladder dose
KW - Dose-effect relations
KW - External beam radiotherapy
KW - Focal boosting
KW - Genitourinary toxicity
KW - Prostate cancer
KW - Urethral dose
UR - https://www.scopus.com/pages/publications/85122310265
U2 - 10.1016/j.radonc.2021.12.027
DO - 10.1016/j.radonc.2021.12.027
M3 - Article
C2 - 34968470
SN - 0167-8140
VL - 167
SP - 127
EP - 132
JO - Radiotherapy & Oncology
JF - Radiotherapy & Oncology
ER -