Risk factors and dose-effects for bladder fistula, bleeding and cystitis after radiotherapy with imaged-guided adaptive brachytherapy for cervical cancer: An EMBRACE analysis

Purpose: To identify patient- and treatment-related risk factors for fistula, bleeding, cystitis, pain and difficulty in voiding in locally advanced cervical cancer patients treated with radio(chemo)therapy and image-guided adaptive brachytherapy (IGABT). Material and methods: Morbidity within the EMBRACE-I study was prospectively reported for physician-assessed (CTCAE) fistula, bleeding and cystitis and patient-reported (EORTC) pain and difficulty in voiding. Analysis of risk factors was performed in patients without bladder infiltration. Risk factors were tested with Cox regression for grade (G) >= 3 cystitis, for G >= 2 fistula, bleeding and cystitis, and for EORTC very much and quite a bit or worse. Results: Of 1416 patients enrolled, 1153 and 884 patients without bladder infiltration were evaluable for the analysis of CTCAE and EORTC items, respectively. Median follow-up was 48[3-120] months. Crude incidence rates for G >= 2 fistula, bleeding and cystitis were 0.7%, 2.7% and 8.8%, respectively, and 16% and 14% for quite a bit or worse pain and difficulty in voiding, respectively. Baseline urinary morbidity and overweight/obesity were significant risk factors for most endpoints. Bladder D-2cm3 correlated with G >= 2 fistula, bleeding and cystitis, while ICRU bladder point dose correlated with EORTC pain quite a bit or worse. An increase from 75 Gy to 80 Gy in bladder D-2cm3 resulted in an increase from 8% to 13% for 4-year actuarial estimate of G >= 2 cystitis. Conclusion: Clinical and treatment-related risk factors for bladder fistula, bleeding and cystitis were identified within a prospective and multi-institutional setting. A dose-effect was established with bladder D-2cm3, reinforcing the importance of continued optimization during individualized IGABT planning. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study aimed to identify patient- and treatment-related risk factors for complications in locally advanced cervical cancer patients receiving radiotherapy and IGABT. The results showed that baseline urinary morbidity and overweight/obesity were significant risk factors for most endpoints, and a dose-effect was established with bladder D-2cm3 for fistula, bleeding, and cystitis.