Importance of the ICRU bladder point dose on incidence and persistence of urinary frequency and incontinence in locally advanced cervical cancer: An EMBRACE analysis

Authors Sofia Spampinato, Lars U Fokdal, Richard Pötter, Christine Haie-Meder, Jacob C Lindegaard, Maximilian P Schmid, Alina Sturdza, Ina M Jürgenliemk-Schulz, Umesh Mahantshetty, Barbara Segedin, Kjersti Bruheim, Peter Hoskin, Bhavana Rai, Fleur Huang , Rachel Cooper, Elzbieta van der Steen-Banasik, Erik Van Limbergen, Marit Sundset, Henrike Westerveld, Remi A Nout, Nina B K Jensen, Christian Kirisits, Kathrin Kirchheiner, Kari Tanderup, EMBRACE Collaborative Group
Source Radiother Oncol. 2021 May;158:300-308 Publicationdate 14 Oct 2020
Abstract

Abstract

Purpose: To identify patient- and treatment-related risk factors and dose-effects for urinary frequency and incontinence in locally advanced cervical cancer (LACC) treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT).

Material and methods: Physician-assessed (CTCAE) and patient-reported (EORTC) frequency and incontinence recorded in the EMBRACE-I study were analysed. Risk factors analysis was performed in patients without bladder infiltration and with baseline morbidity available. Cox regression was used for CTCAE grade (G) ≥ 3 and G ≥ 2 and for EORTC "very much" and "quite a bit" or worse. Logistic regression was used for late persistent morbidity defined when CTCAE G ≥ 1 or EORTC ≥ "quite a bit" were scored in at least half of follow-ups.

Results: Longitudinal data on 1153 and 884 patients were available for CTCAE and EORTC analysis, respectively. Median follow-up was 48[3-120] months. Crude incidence rates of G≥2 were 13% and 11% for frequency and incontinence, respectively. Baseline morbidity and overweight-obesity were risk factors for both symptoms. Elderly patients were at higher risk for incontinence. Patients receiving conformal-radiotherapy were at higher risk for frequency. ICRU bladder point (ICRU-BP) dose was a stronger predictor for incontinence than bladder D2cm3. The 5-year actuarial estimate of G ≥ 2 incontinence increased from 11% to 20% with ICRU-BP doses > 75 Gy compared to ≤ 65 Gy. Frequency showed weaker associations with dose.

Conclusion: ICRU-BP dose, in addition to clinical parameters, is a risk factor for urinary incontinence and shows a dose-effect after radio(chemo)therapy and IGABT. ICRU-BP dose should be monitored during treatment planning alongside volumetric parameters. Frequency seems associated with larger irradiated volumes.

Keywords: Cervical cancer; Clinical study; Dose-effect relationship; IGABT; Risk factors; Urinary morbidity.