HBOT for Haemorrhagic Cystitis Following Radiotherapy or Chemotherapy

Article
Dr Nur's profile photo
DrNur Ozyilmaz, MD
Founder · NUMA

Key Takeaways

  • Haemorrhagic cystitis (HC) is characterised by inflammation and bleeding of the bladder lining. While it can occur for several reasons, in cancer patients it is most commonly associated with pelvic radiotherapy, certain chemotherapy agents, and haematopoietic stem cell transplantation (HSCT). 1 2 3
  • Hyperbaric oxygen therapy (HBOT) is a medical treatment in which patients breathe near-100% oxygen in a pressurised chamber, significantly increasing the amount of oxygen dissolved in the bloodstream and delivered throughout the body. In haemorrhagic cystitis, HBOT is used to support healing of damaged bladder tissue by improving tissue oxygenation, promoting new blood vessel formation, and enhancing repair processes. 4 5 6
  • A typical HBOT course involves 30-40 treatment sessions, usually delivered five days per week, with each session lasting approximately 90-120 minutes. 7 8 9
  • The strongest evidence supports HBOT for radiation-induced haemorrhagic cystitis, where studies have demonstrated improvements in haematuria, urinary symptoms, and quality of life. 7 8 10 11 9 12
  • Evidence for chemotherapy-induced and HSCT-associated haemorrhagic cystitis is more limited but suggests HBOT may benefit selected patients with persistent symptoms. 13 14 15 3
  • When delivered in accredited hyperbaric centres under specialist medical supervision, HBOT has a well-established safety profile, with most side effects being mild and temporary. 4 5 11
  • HBOT is generally considered when haematuria persists or recurs despite appropriate conventional management and specialist evaluation. It should be considered an adjunctive treatment within a multidisciplinary care pathway rather than a replacement for standard care. Depending on the underlying cause and severity of symptoms, management may involve urologists, oncologists, radiation oncologists, interventional radiologists, and hyperbaric medicine specialists. Patients with significant bleeding, clot retention, infection, anaemia, urinary tract obstruction, severe pain, or concern for recurrent malignancy require prompt specialist assessment and coordinated management. 1 2

Quick Summary

Haemorrhagic cystitis (HC) is a condition characterised by inflammation and bleeding of the bladder lining. In the oncology setting, it is most commonly associated with pelvic radiotherapy, certain chemotherapy agents, and haematopoietic stem cell transplantation (HSCT). 1 2 3

Common symptoms include:

  • Visible blood in the urine (haematuria)
  • Urinary frequency and urgency
  • Pain or burning when passing urine
  • Nocturia (frequent urination at night)
  • Passage of blood clots
  • Difficulty emptying the bladder
  • Fatigue related to blood loss or anaemia

Symptoms can range from mild intermittent bleeding to severe haematuria requiring hospitalisation, blood transfusions, or intervention to relieve clot retention. 1 2

Radiation-induced haemorrhagic cystitis is a recognised late effect of pelvic radiotherapy. Symptoms most commonly develop 1-3 years after treatment, although they can occur as early as 6 months or as late as 20 years later. The underlying bladder injury often involves damage to small blood vessels, chronic inflammation, reduced tissue oxygenation, and impaired healing, all of which can contribute to recurrent or persistent bleeding. 1 16 6

Hyperbaric oxygen therapy (HBOT) has emerged as a potential treatment option because it targets these underlying biological processes. By increasing tissue oxygen availability, HBOT may promote new blood vessel formation, support tissue repair, improve healing within damaged bladder tissue, and help address the chronic hypoxia and inflammation that contribute to ongoing bladder injury. 4 5 6 7

The strongest evidence for HBOT comes from radiation-induced haemorrhagic cystitis, where clinical trials, systematic reviews, meta-analyses, and long-term follow-up studies have reported improvements in haematuria, urinary symptoms, and quality of life. By addressing the underlying tissue damage rather than simply treating symptoms, HBOT has become an evidence-supported adjunctive treatment option for appropriately selected patients with persistent or recurrent radiation-induced haemorrhagic cystitis. 7 8 10 11 9 12

Evidence for chemotherapy-induced and HSCT-associated haemorrhagic cystitis is more limited and is derived primarily from retrospective studies and case series. However, published reports have described improvements in haematuria and symptom control in selected patients with persistent or treatment-refractory disease, supporting continued investigation of HBOT in these settings. 13 14 15 3

The following sections review the biological rationale, clinical evidence, and current role of HBOT in the management of haemorrhagic cystitis.

What is HBOT?

Hyperbaric oxygen therapy (HBOT) is a physician-prescribed medical treatment in which patients breathe 100% oxygen inside a specially designed pressurised chamber. The increased pressure allows substantially more oxygen to dissolve into the blood plasma, enhancing oxygen delivery to tissues throughout the body, including areas with impaired blood supply or chronic injury. 4 5

In haemorrhagic cystitis, this matters because radiation- and chemotherapy-related bladder injury often behaves like a chronic wound-healing problem: the tissue is inflamed, poorly oxygenated, fragile, and prone to recurrent bleeding. HBOT is therefore used as a tissue-repair strategy within a coordinated clinical pathway. 1 16 6 7

In published radiation cystitis protocols, treatment commonly involves around 30-40 sessions, often delivered once daily, five days per week, with each session lasting around 90-120 minutes. Individual protocols vary by centre, patient tolerance, severity of bleeding, and clinical response. 7 8 9

Biological Rationale for HBOT

The rationale is strongest in radiation-induced disease. Pelvic radiotherapy can damage the bladder lining, blood vessels and deeper supporting tissues. Over time, this can lead to reduced vascularity, hypoxia, fibrosis, chronic inflammation, fragile telangiectatic vessels, and recurrent haematuria. 1 16 6

HBOT may help by supporting several oxygen-dependent repair processes:

  • Increasing dissolved oxygen in plasma, which improves the oxygen gradient into hypoxic tissue. 4 5
  • Promoting angiogenesis and neovascularisation, helping restore microvascular blood supply in damaged tissue. 4 6 7
  • Supporting fibroblast activity, collagen formation, epithelial repair and wound healing. 4 5 6
  • Helping to address the chronic hypoxia and inflammatory changes that contribute to ongoing tissue injury. 16 6

In chemotherapy-induced and HSCT-associated haemorrhagic cystitis, the initial trigger may be different. Cyclophosphamide and ifosfamide can injure the bladder lining through toxic urinary metabolites, while transplant-associated disease may involve conditioning chemotherapy, viral reactivation such as BK virus, thrombocytopenia, infection risk and immune-mediated injury. Even so, the repair logic remains clinically relevant: HBOT may support healing of injured urothelium and damaged microvasculature in selected patients. 13 14 15 3

What Does the Evidence Show?

1. Radiotherapy-induced haemorrhagic cystitis: strongest evidence

Radiotherapy-induced haemorrhagic cystitis is the most extensively studied indication for HBOT in this setting. The evidence base includes randomised trial data, long-term follow-up, systematic reviews, meta-analyses and multicentre registry evidence. 7 8 10 11 9

The RICH-ART trial is the key landmark study. In this Nordic randomised phase 2-3 trial, patients with chronic radiation cystitis were randomised to HBOT or standard care. HBOT produced a significantly greater improvement in patient-reported urinary quality-of-life symptoms at 6-8 months, with a between-group Expanded Prostate Cancer Index Composite (EPIC) urinary total score difference of 10.1 points. Reported adverse events were generally transient and mild, mainly grade 1-2 visual or hearing-related effects. 7

The 5-year RICH-ART follow-up is particularly important because radiation cystitis is often a long-term condition. Symptom improvement was sustained over five years: the mean EPIC urinary total score improved by approximately 18 points at 6 months and remained about 19 points at 5 years, with 68.6% of patients classified as responders. 8

A 2024 systematic review and meta-analysis pooled 14 studies including 556 patients with radiation-induced haemorrhagic cystitis. Across the pooled data, 89.9% of patients had symptom improvement; estimated complete haematuria remission was 55%, with partial remission in approximately 35%. The authors also noted important limitations, including variation in protocols, outcome tools and study designs. 10

The 2023 Cochrane review concluded that HBOT may improve outcomes in selected people with late radiation tissue injury affecting the bladder and lower bowel, while emphasising that certainty varies by outcome and that further work is needed to define optimal timing, dose and patient selection. 11

Real-world registry evidence adds clinical relevance. In a multicentre registry cohort of 470 patients treated for radiation cystitis, median treatment was 39 sessions and patient-reported haematuria and urinary distress scores improved after HBOT. 9 Patient-reported long-term outcome data also suggest reductions in symptom severity, anxiety related to bleeding and healthcare utilisation after HBOT, although ongoing haematuria can persist in some patients. 12

Overall, the radiation-induced evidence supports a confident and balanced conclusion: HBOT is a credible bladder-sparing adjunct for appropriately selected patients with persistent or recurrent radiation cystitis symptoms, particularly haematuria, after specialist assessment and initial management. 2 7 8 10 11 9 12

2. Chemotherapy-induced and HSCT-associated haemorrhagic cystitis: promising but less mature evidence

The evidence for chemotherapy-induced and HSCT-associated haemorrhagic cystitis is smaller and less definitive than for radiation-induced disease. It is based mainly on retrospective cohorts, case series and transplant populations rather than large randomised trials. 13 14 15 3

Davis et al. (2011) reported six cases of life-threatening cyclophosphamide-induced haemorrhagic cystitis treated with HBOT. Bleeding stopped in all six patients after 14-40 treatments, no complications were reported, and patients remained clear of haematuria during 11-36 months of follow-up. This is a small case series, but clinically relevant because the cases were severe. 14

Degener et al. (2015) reported long-term experience with HBOT in refractory radio- or chemotherapy-induced haemorrhagic cystitis. The authors concluded that HBOT was a safe and effective option in treatment-resistant cases, while also calling for prospective trials. 13

For HSCT-associated haemorrhagic cystitis, Arana Ribeiro et al. (2024) reported a retrospective cohort over 25 years. Patients received daily HBOT, and complete or partial clinical responses were reported in a substantial proportion of cases. Having at least 10 HBOT sessions was associated with a higher likelihood of response. The authors supported an adjunctive role for HBOT while recommending randomised trials. 15

Aldiwani et al. (2019) systematically reviewed BK virus-associated haemorrhagic cystitis and found that the broader treatment evidence remains limited and generally low quality. This reinforces the need for multidisciplinary management involving haematology, urology, infectious diseases and hyperbaric medicine where appropriate. 3

The balanced clinical message is persuasive but honest: HBOT is biologically rational and clinically promising for selected chemotherapy- or transplant-associated cases, especially where bleeding is persistent or refractory, but the evidence base is not yet as strong as it is for radiation-induced haemorrhagic cystitis. 13 14 15 3

HBOT Care Strategy

HBOT is most effective when used as part of a multidisciplinary care pathway rather than as an isolated last-line option. Before considering treatment, the cause of bleeding should be established and urgent complications addressed. This may include investigation for infection, stones, catheter-related trauma, recurrent malignancy, or other causes of haematuria, together with appropriate blood tests, imaging, cystoscopy, or urine studies where indicated. 1 2

Patients with significant bleeding, clot retention, anaemia, sepsis, severe pain, or urinary tract obstruction require prompt specialist assessment and conventional management before HBOT is considered. 1 2

HBOT may be appropriate for selected patients with:

  • Persistent or recurrent haematuria following pelvic radiotherapy.
  • Radiation cystitis symptoms affecting quality of life.
  • Chemotherapy-induced haemorrhagic cystitis that remains problematic despite standard medical treatment.
  • HSCT-associated haemorrhagic cystitis where ongoing tissue injury contributes to prolonged bleeding.
  • A desire to pursue a bladder-sparing treatment approach where clinically appropriate.

Treatment is typically delivered under specialist supervision over approximately 30-40 sessions, although protocols vary according to the underlying condition and individual response. 4 5 7 8

Evidence suggests that earlier referral may be associated with better outcomes in radiation-induced haemorrhagic cystitis, particularly before chronic tissue injury becomes advanced. 2 13 Throughout treatment, progress should be assessed using outcomes that matter to patients, including bleeding severity, urinary symptoms, quality of life, hospital admissions, transfusion requirements, and overall functional recovery.

Persistent or recurrent haematuria should always prompt reassessment, as bleeding may not necessarily be attributable to previous cancer treatment alone. 1 2

Safety and Patient Experience

Like all medical treatments, hyperbaric oxygen therapy (HBOT) carries potential risks and side effects. For this reason, treatment should be delivered in an accredited medical facility under the supervision of appropriately trained hyperbaric medicine specialists.

HBOT is generally well tolerated and has a well-established safety profile when delivered according to recognised clinical protocols. The most commonly reported side effects are ear pressure or middle-ear barotrauma, sinus discomfort, temporary visual changes, fatigue, and anxiety in confined spaces. Very rare complications include oxygen-induced seizures and pulmonary barotrauma, with oxygen-related seizures reported in only a small fraction of treatments. 4 5 11

Careful patient selection, pre-treatment assessment, ongoing monitoring, and adherence to established safety procedures help minimise risk and optimise the treatment experience.

Summary

Hyperbaric oxygen therapy (HBOT) is an evidence-supported adjunctive treatment for selected patients with haemorrhagic cystitis, particularly those with persistent or recurrent symptoms following pelvic radiotherapy. By addressing the underlying tissue injury associated with chronic bladder damage, HBOT may help improve haematuria, urinary symptoms, and quality of life in appropriately selected patients. When delivered in accredited centres under specialist supervision, HBOT has a well-established safety profile and is generally well tolerated, with most side effects being mild and temporary. 7 8 10 11 9 12

The evidence for chemotherapy-induced and HSCT-associated haemorrhagic cystitis is less mature but remains encouraging, with published studies supporting a potential role for HBOT in selected refractory cases. 13 14 15 3

HBOT should be considered within a multidisciplinary care pathway involving urologists, oncologists, radiation oncologists, interventional radiologists, haematologists, and hyperbaric medicine specialists where appropriate. For patients with radiation-induced haemorrhagic cystitis, the combination of biological plausibility, randomised trial data, long-term follow-up, and real-world clinical outcomes supports HBOT as a credible and increasingly established treatment option. Further research will continue to refine patient selection and optimise treatment protocols, but the current evidence provides a strong foundation for its use in appropriately selected patients. 7 8 10 11 9 12 13 14 15 3 17

References

Footnotes

  1. Horan N, Cooper JS. Radiation Cystitis and Hyperbaric Management. StatPearls. NCBI Bookshelf. Updated 2023. https://www.ncbi.nlm.nih.gov/books/NBK470594/ ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10
  2. Goucher G, Saad F, Lukka H, Kapoor A. Canadian Urological Association Best Practice Report: Diagnosis and management of radiation-induced hemorrhagic cystitis. Can Urol Assoc J. 2019;13(2):15-23. https://doi.org/10.5489/cuaj.5788 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9
  3. Aldiwani M, Tharakan T, Al-Hassani A, Gibbons N, Pavlu J, Hrouda D. BK virus-associated haemorrhagic cystitis: a systematic review of current prevention and treatment strategies. Int J Surg. 2019;63:34-42. https://doi.org/10.1016/j.ijsu.2019.01.019 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10
  4. Undersea and Hyperbaric Medical Society (UHMS). Delayed Radiation Injury (Soft Tissue and Bony Necrosis). UHMS. https://www.uhms.org/11-delayed-radiation-injury-soft-tissue-and-bony-necrosis.html ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9
  5. Mayo Clinic. Hyperbaric oxygen therapy: overview, procedure and risks. Updated 2024. https://www.mayoclinic.org/tests-procedures/hyperbaric-oxygen-therapy/about/pac-20394380 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8
  6. Helissey C, Cavallero S, Brossard C, Dusaud M, Chargari C, François S. Chronic Inflammation and Radiation-Induced Cystitis: Molecular Background and Therapeutic Perspectives. Cells. 2020;10(1):21. https://doi.org/10.3390/cells10010021 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8
  7. Oscarsson N, Müller B, Rosén A, et al. Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2-3 trial. Lancet Oncol. 2019;20(11):1602-1614. https://doi.org/10.1016/S1470-2045(19)30494-2 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11 ↩12 ↩13
  8. Oscarsson N, Rosén A, Müller B, et al. Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): long-term follow-up of a randomised, controlled, phase 2-3 trial. EClinicalMedicine. 2025;83:103214. https://doi.org/10.1016/j.eclinm.2025.103214 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10
  9. Moses RA, Hunter AE, Brandes ER, et al. Patient-Reported Outcome Measures Following Hyperbaric Oxygen Therapy for Radiation Cystitis: Early Results From the Multicenter Registry for Hyperbaric Oxygen Therapy. J Urol. 2024;211(6):765-774. https://doi.org/10.1097/JU.0000000000003929 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9
  10. Yang TK, Wang YJ, Li HJ, Yu YF, Huang KW, Cheng JCH. Efficacy and Safety of Hyperbaric Oxygen Therapy for Radiation-Induced Hemorrhagic Cystitis: A Systematic Review and Meta-Analysis. J Clin Med. 2024;13(16):4724. https://doi.org/10.3390/jcm13164724 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7
  11. Lin ZC, Bennett MH, Hawkins GC, Azzopardi CP, Feldmeier J, Smee R, Milross C. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev. 2023;8:CD005005. https://doi.org/10.1002/14651858.CD005005.pub5 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9
  12. Milton T, Noll D, Stapleton P, et al. Long-Term Patient-Reported Outcomes of Hyperbaric Oxygen Therapy for Haematuria Due to Radiation Cystitis Secondary to External Beam Radiotherapy for Pelvic Malignancy. Soc Int Urol J. 2025;6(5):66. https://doi.org/10.3390/siuj6050066 ↩ ↩2 ↩3 ↩4 ↩5 ↩6
  13. Degener S, Pohle A, Strelow H, et al. Long-term experience of hyperbaric oxygen therapy for refractory radio- or chemotherapy-induced haemorrhagic cystitis. BMC Urol. 2015;15:38. https://doi.org/10.1186/s12894-015-0035-4 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9
  14. Davis M, MacDonald H, Sames C, Nand K. Severe cyclophosphamide-induced haemorrhagic cystitis treated with hyperbaric oxygen. N Z Med J. 2011;124(1340):48-54. https://pubmed.ncbi.nlm.nih.gov/21952384/ ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8
  15. Arana Ribeiro JA, Costa DA, Gaio-Lima C, et al. Hyperbaric oxygen therapy in the treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. Sci Rep. 2024;14:25321. https://doi.org/10.1038/s41598-024-74858-8 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8
  16. Zwaans BMM, Chancellor MB, Lamb LE. Challenges and Opportunities in Radiation-induced Hemorrhagic Cystitis. Rev Urol. 2016;18(2):57-65. https://pmc.ncbi.nlm.nih.gov/articles/PMC5010626/ ↩ ↩2 ↩3 ↩4
  17. ClinicalTrials.gov. Chronic Radiation Cystitis and Effect of Hyperbaric Oxygen Therapy on Patient Reported Outcomes and Urine Inflammatory Biomarkers. NCT07368647. https://clinicaltrials.gov/study/NCT07368647 ↩