Scoping Review and Meta-analysis of Hyperbaric Oxygen Therapy for Radiation-Induced Hemorrhagic Cystitis
Purpose of review
To critically review and summarize existing literature assessing the effectiveness of hyperbaric oxygen therapy (HBOT) for the treatment of radiation-induced urologic injury.
Though 5 of the included 13 studies were published in the last 2–3 years, the only randomized controlled study was performed in 2012. Recent studies have confirmed the safety and efficacy of HBOT as well as identified risk factors for success vs. failure of HBOT for hemorrhagic radiation cystitis (HRC).
Of the 602 patients that received HBOT for HRC, 84% had a partial or complete resolution. In the 7 studies that utilized RTOG/EORTC, 75% of patients saw an improvement in hematuria of at least one grade (out of possible 5 total). Of the 499 patients with documented follow-up, 14% experienced recurrence, with a median time to recurrence of 10 months (6 to 16.5 months).
KeywordsHyperbaric oxygen therapy HBOT Hemorrhagic radiation cystitis Radiation cystitis Urologic radiation injury Radiation-induced urethral stricture
Compliance with Ethical Standards
Conflict of Interest
James Cardinal, Austen Slade, Mary McFarland, Sorena Keihani, and James N. Hotaling each declare no potential conflicts of interest.
Jeremy B. Myers reports grants from PCORI Foundation, Department of Defense, and Boston Scientific.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.Global Burden of Disease Cancer C, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol. 2017;3(4):524–48. https://doi.org/10.1001/jamaoncol.2016.5688.CrossRefGoogle Scholar
- 9.Gaffney DK, Jhingran A, Portelance L, Viswanathan A, Schefter T, Weidhaas J, et al. Radiation therapy oncology group gynecologic oncology working group: comprehensive results. Int J Gynecol Cancer. 2014;24(5):956–62. https://doi.org/10.1097/IGC.0000000000000135. CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Corman JM, McClure D, Pritchett R, Kozlowski P, Hampson NB. Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen. J Urol. 2003;169(6):2200–2. https://doi.org/10.1097/01.ju.0000063640.41307.c9. CrossRefPubMedGoogle Scholar
- 15.Wein AJ, Kavoussi LR, Partin AW, Peters C. Campbell-Walsh urology. 11th ed. Philadelphia: Elsevier; 2016.Google Scholar
- 16.Feldmeier JJ, Undersea, Hyperbaric Medical S. Hyperbaric oxygen 2003: indications and results: the hyperbaric oxygen therapy committee report. Kensington: Undersea and Hyperbaric Medical Society; 2003.Google Scholar
- 20.Bennett MH, Feldmeier J, Hampson N, Smee R, Milross C. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2012;5:CD005005.Google Scholar
- 23.•• Mougin J, Souday V, Martin F, Azzouzi AR, Bigot P. Evaluation of hyperbaric oxygen therapy in the treatment of radiation-induced hemorrhagic cystitis. Urology. 2016;94:42–6. https://doi.org/10.1016/j.urology.2016.04.015. A retrospective study of a cohort of 71 patients using HBOT to treat post-radiation hematuria. Gross decrease in hematuria was seen in 65% ( n = 46) of patients. Of the 46 patients that saw resolution, 19 patients had relapse of symptoms within the median follow-up time of 15 months. A hematuria grade of less than III was predictive for a successful outcome (hazard ratio [HR] 4.4; P = .01). Anticoagulant therapy was predictive for treatment failure (HR 0.3; P = .03). CrossRefPubMedGoogle Scholar
- 24.O'Reilly KJ, Hampson NB, Corman JM. Hyperbaric oxygen in urology. AUA Update Series. 2002.Google Scholar
- 34.•• Ribeiro de Oliveira TM, Carmelo Romao AJ, Gamito Guerreiro FM, Matos Lopes TM. Hyperbaric oxygen therapy for refractory radiation-induced hemorrhagic cystitis. Int J Urol. 2015;22(10):962–6. https://doi.org/10.1111/iju.12857. A retrospective study of a cohort of 176 patients using HBOT for treatment of radiation-induced hemorrhagic cystitis. Indication for radiation therapy included a large number of patients with for uterine cervix cancer ( n = 89) and prostate cancer ( n = 56). Gross decrease in hematuria was seen in 90% ( n = 158) in patients undergoing HBOT. No significant difference between patients with resolution as compared to patients without resolution was seen when type of malignancy, namely uterine cervix cancer and prostate cancer, was considered. CrossRefPubMedGoogle Scholar
- 37.Dellis A, Deliveliotis C, Kalentzos V, Vavasis P, Skolarikos A. Is there a role for hyberbaric oxygen as primary treatment for grade IV radiation-induced haemorrhagic cystitis? A prospective pilot-feasibility study and review of literature. Int Braz J Urol. 2014;40(3):296–305. https://doi.org/10.1590/S1677-5538.IBJU.2014.03.02.CrossRefPubMedGoogle Scholar
- 39.• Neheman A, Nativ O, Moskovitz B, Melamed Y, Stein A. Hyperbaric oxygen therapy for radiation-induced haemorrhagic cystitis. BJU Int. 2005;96(1):107–9. https://doi.org/10.1111/j.1464-410X.2005.05577.x. A retrospective study of a cohort of 25 patients using HBOT for treatment of chronic radiation-induced tissue injuries, of which, five were treated for urethral stricture. Four of the five patients with urethral stricture saw improvement of stricture with HBOT. CrossRefPubMedGoogle Scholar
- 40.Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. (Clinical research ed.). 2011 Oct 18;343(7829):d5928. https://doi.org/10.1136/bmj.d5928.
- 41.The Ottawa Hospital Research Institute. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2011. http://www.ohri.ca/Programs/clinical_epidemiology/oxford.asp. Accessed 12/08/2017 2017.
- 44.Foundation. BR. Study to determine if hyperbaric oxygen therapy is helpful for treating radiation tissue injuries. In: In ClinicalTrials.gov [Internet].. Bethesda (MD): U.S. National Library of Medicine. 2000 -. 2001. Available from: https://ClinicalTrials.gov/show/NCT00134628. Accessed 2005 Aug 23 [last updated 2016 Jan 12; terminated; cited 2018 Jan 10]. 2018.
- 45.Göteborg University | Sahlgrenska University Hospital. Radiation induced cystitis treated with hyperbaric oxygen—a randomized controlled trial. In: In ClinicalTrials.gov [Internet].. Bethesda (MD): U.S. National Library of Medicine. 2000 -. 2012. Available from: https://ClinicalTrials.gov/show/NCT01659723. 2018.
- 46.Clarke RE, Tenorio LM, Hussey JR, Toklu AS, Cone DL, Hinojosa JG, et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. Int J Radiat Oncol Biol Phys. 2008;72(1):134–43. https://doi.org/10.1016/j.ijrobp.2007.12.048.CrossRefPubMedGoogle Scholar