To assess the efficacy and safety of intravesical instillation of high molecular weight sodium hyaluronate (HMW-HA) for the treatment of radiation-induced cystitis.
This prospective cohort study was conducted in seven centers in France. Eligible patients with radiation-induced cystitis were recruited between April 2020 and March 2021. A sterile disposable 50 ml prefilled solution containing 0.16% (80 mg/50 mL) HMW-HA (INSTYLAN) was instilled weekly into the bladder. The treatment consisted of 6 sessions (V1 to V6). Outcomes were assessed 1 week (V7) and 4 weeks (V8) after the last session and were compared with baseline (V0). The primary endpoint was bladder pain, evaluated by a Questionnaire with 5 closed-ended response options. Secondary endpoints included changes from baseline for hematuria, urinary frequency, and the effect of urgencies on Quality of Life (QoL). Adverse events (AEs) were graded according to the CTCAE 3.0 classification.
A total of 30 participants were enrolled. The Intent-to-Treat analysis showed a significant reduction in pelvic pain intensity (− 45.81%, p < 0.001), hematuria (− 26.87%, p = 0.008), total 24 h voids (− 23.92%, p < 0.001) and the effect of urgencies on QoL (− 33.92%, p < 0.001) at V7. The improvement for each outcome remained stable during the post-therapeutic period between V7 and V8. Bladder instillation therapy was well-tolerated: two treatment-related AEs (6.6%) were reported corresponding to two grade 1 hematuria.
Intravesical instillation of HMW-HA appears to be effective in the treatment of radiation-induced cystitis. Further comparative studies with longer follow-up are needed to confirm our preliminary results.
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Matz EL, Hsieh MH (2017) Review of advances in uroprotective agents for cyclophosphamide- and ifosfamide-induced hemorrhagic cystitis. Urology 100:16–19
Payne H, Adamson A, Bahl A et al (2013) Chemical- and radiation-induced haemorrhagic cystitis: current treatments and challenges. BJU Int 112:885
Fransson P, Widmark A (1999) Late side effects unchanged 4–8 years after radiotherapy for prostate carcinoma: a comparison with age-matched controls. Cancer 85:678–688
Mendenhall WM, Henderson RH, Costa JA et al (2015) Hemorrhagic radiation cystitis. Am J Clin Oncol 38(3):331–336
Ribeiro de Oliveira TM, Carmelo Romao AJ, Gamito Guerreiro FM, Matos Lopes TM (2015) Hyperbaric oxygen therapy for refractory radiation-induced hemorrhagic cystitis. Int J Urol 22:962–966
Oscarsson N, Müller B, Rosén A et al (2019) Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial. Lancet Oncol 20(11):1602–1614
Zwaans BM, Chancellor MB, Lamb LE (2016) Modeling and treatment of radiation cystitis. Urology 88:14–21
Browne CD, Davis NF, Mac Craith E et al (2015) A narrative review on the pathophysiology and management for radiation cystitis. Adv Urol 2015:346812
Pascoe C, Duncan C, Lamb BW et al (2019) Current management of radiation cystitis: a review and practical guide to clinical management. BJU Int 123(4):585–594
Shao Y, Lu GL, Shen ZJ (2012) Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis. BJU Int 109(5):691–694
Lazzeri ML, Hurle R, Casale P et al (2016) Managing chronic bladder diseases with the administration of exogenous glycosaminoglycans: an update on the evidence. Ther Adv Urol 8:91–99
Wyndaele JJJ, Riedl C, Taneja R, Lovász S, Ueda T, Cervigni M (2019) GAG replenishment therapy for bladder pain syndrome/interstitial cystitis. Neurourol Urodyn 38(2):535–544
Morales A, Emerson L, Nickel JC (1997) Intravesical hyaluronic acid in the treatment of refractory interstitial cystitis. Urology 49:111–113
Shao Y, Shen ZJ, Rui WB, Zhou WL (2010) Intravesical instillation of hyaluronic acid prolonged the effect of bladder hydrodistention in patients with severe interstitial cystitis. Urology 75:547–550
Ahmad I, Sarath Krishna N, Meddings RN (2008) Sequential hydrodistension and intravesical instillation of hyaluronic acid under general anaesthesia for treatment of refractory interstitial cystitis: a pilot study. Int Urogynecol J Pelvic Floor Dysfunct 19(4):543–546
Sommariva ML, Sandri SD, Ceriani V (2010) Efficacy of sodium hyaluronate in the management of chemical and radiation cystitis. Minerva Urol Nefrol 62(2):145–150
Miodosky M, Abdul-Hai A, Tsirigotis P et al (2006) Treatment of post-hematopoietic stem cell transplantation hemorrhagic cystitis with intravesicular sodium hyaluronate. Bone Marrow Transplant 38(7):507–511
Constantinides C, Manousakas T, Nikolopoulos P, Stanitsas A, Haritopoulos K, Giannopoulos A (2004) Prevention of recurrent bacterial cystitis by intravesical administration of hyaluronic acid: a pilot study. BJU Int 93(9):1262–1266
Cardinal J, Slade A, McFarland M et al (2018) Scoping review and meta-analysis of hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis. Curr Urol Rep 19:38
Madhuvrata P, Singh M, Hasafa Z, Abdel-Fattah M (2012) Anticholinergic drugs for adult neurogenic detrusor overactivity: a systematic review and meta-analysis. Eur Urol 62(5):816–830
Redorta JP, Sanguedolce F, Pardo GS et al (2021) Multicentre international study for the prevention with iAluRil of radio-induced cystitis (MISTIC): a randomised controlled study. Eur Urol Open Sci 23(26):45–54
Westerman ME, Boorjian SA, Linder BJ (2016) Safety and efficacy of intravesical alum for intractable hemorrhagic cystitis: a contemporary evaluation. Int Braz J Urol 42:1144–1149
Phelps KR, Naylor K, Brien TP et al (1999) Encephalopathy after bladder irrigation with alum: case report and literature review. Am J Med Sci 318:181–185
Shah BC, Albert DJ (1973) Intravesical instillation of formalin for the management of intractable hematuria. J Urol 110:519–520
Lojanapiwat B, Sripralakrit S, Soonthornphan S (2002) Intravesicle formalin instillation with a modified technique for controlling haemorrhage secondary to radiation cystitis. Asian J Surg 25:232–235
Dewan AK, Mohan GM, Ravi R (1993) Intravesical formalin for hemorrhagic cystitis following irradiation of cancer of the cervix. Int J Gynaecol Obstet 42:131–135
The study was funded by LIDDE Therapeutics SAS.
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The authors report no conflict of interest.
The study protocol and amendments were approved by the Committee for the Protection of Persons: CPP Sud-Est VI—Clermont Ferrand.
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Patient’s written information and participation agreement was obtained and signed from all patients.
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We would like to pay tribute to the memory of Mr. Francois Schutz, chairman of LIDDE Therapeutics.
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Baboudjian, M., Fourmarier, M., Clement, C. et al. Intravesical instillation of high molecular weight sodium hyaluronate in radiation-induced cystitis: a prospective pilot study. World J Urol (2021). https://doi.org/10.1007/s00345-021-03837-9
- Sodium hyaluronate
- Intravesical instillation
- Radiation-induced cystitis
- Bladder pain