Intravesical instillation with glycosaminoglycan replacement treatment in patients suffering radiation-induced haemorrhagic cystitis: When and which patients can benefit most from it?

INTRODUCTION & OBJECTIVES: Radiation-induced haemorrhagic cystitis (RHC) is a frightening complication occurring after pelvic radiotherapy (PRT) which may significantly affect patients' quality of life. Bladder instillation with glycosaminoglycan replacement therapy (GRT) including hyaluronic acid +/- chondroitin sulphate has been proposed as an emerging alternative to prevent relapses of haematuria. Strong points in favour of using GRT for RHC are the ease of administration, cost, almost absence of side effects and possibility of administration to outpatients. We investigated the effectiveness of GRT in a cohort, single-centre, of patients with past-medical history of PRT attending the outpatient clinic and/or the accident & emergency department (A&E) for RHC. MATERIALS & METHODS: Patients with diagnosis of RHC, either with toxicity grade of 2 or 3, were deemed candidate for GRT as long as no active bleeding was occurring; in the case of non-self-limiting haematuria and/or anaemia for active bleeding, admission in the urology department was prompted for bleeding control prior to GRT instillation. An induction course of 6 weekly instillations was scheduled; if tolerated, patients were given a maintenance course with at least 6 monthly instillations. The primary end-point consisted in assessing the rate of haematuria remission (either partial or complete) defined as no need to readmission in the A&E and/or in the hospital. Secondary end-points included factors related to GRT failure. Univariate and multivariate analysis were undertaken to identify clinical independent variables associated to the events. RESULTS: Fifty-one patients with at least 1-year follow-up from the first GRT were included in the analysis. 88.2, 9.8 and 2% of patients had undergone PRT because affected by prostate, uterus and colorectal cancer, respectively. Median time-to-RHC was 31 months (IQR 21-90). Access to A&E and hospital admission were needed in 47 (92.1%) and 35 (68.6%) of the patients, respectively. Twenty-two (n = 22/35, 62.9%) patients required transurethral fulguration of the bladder, while the remainders could be managed with bladder wash-out. Median number of GRT instillations was 6 (IQR 3-7). Twenty-three (45.1%) patients needed to be readmitted to hospital a second time, receiving bladder wash-out (n = 7/23, 30.4%), transurethral fulguration of the bladder (n = 10/23, 43.5%) and/or cystectomy (n = 6/23, 26.1%). Ten (19.6%) patients received a second induction course of GRT. At the last follow-up, 36 (70.6%) patients did not required further hospital admission. Type of PRT and number of hospital admissions pre-GRT were the only variables statistically associated to the events at both univariate (P = 0.032 and P = 0.045) and multivariate analysis (P = 0.048 and P = 0.049). CONCLUSIONS: GRT should be prompted as soon as possible after diagnosis of the haematuria and settling of active bleeding. Patients who had undergone adjuvant PRT after radical prostatectomy are those at higher risk of GRT failure.