Chronic radiation cystitis (RC) unpredictably occurs in more than 10% of patients undergoing radiation for pelvic cancer¹ and can lead to high morbidity and repeated hospital admissions for bleeding complication management. RC begins with radiation-induced bladder mucosal injury, DNA fragmentation, and reactive oxygen species generation,² which perpetuate ongoing inflammatory cytokine and angiogenic growth factor release. In some, this leads to chronic mucosal ischemia ulceration, necrotic fibrosis, and urothelial revascularization with fragile blood vessels prone to clinically significant hemorrhage.³ As the use of multimodal radiation therapy increases and pelvic malignancy survivorship improves, RC incidence and prevalence will likely increase. With nearly 10 million estimated pelvic malignancy survivors by 2026,⁴ there are a significant number of patients at risk. The few existing RC treatments include caustic bladder irrigations, bladder arterial embolization, and bladder removal, which are often associated with poor outcomes.^5,6 Hyperbaric oxygen (HBO₂) therapy (HBOT) is the only noninvasive RC treatment option.

Although not fully understood, theoretically HBOT works by increasing irradiated tissue intravascular oxygen, reducing ischemia, and boosting cellular antioxidant defenses.⁷ Indications for HBO₂ include, but are not limited to, delayed radiation injury such as RC, poor wound healing, and carbon monoxide poisoning. Patients undergo HBO₂ by breathing in 100% oxygen at 1.4 or more atmospheres, typically ranging from 2.0 to 2.4 atmospheres over a series of 40 to 60 sequential treatments.^8,9 There is no consensus on the optimum number of sessions for treatment of RC, though HBO₂ studies suggest 20 treatments or more is associated with greater restorative stem cell mobilization.¹⁰ While cost effective, HBO₂ is expensive, not only the time commitment, but also the estimated cost of $20,000 to $50,000.¹¹

HBO₂ is generally well tolerated, with relatively benign side effects that resolve without intervention as compared to alternative RC therapies. Otic barotrauma is the most common side effect in ∼6% of patients,⁹ which is typically self-limiting. Other reported rare side effects include seizures and visual disturbances. In general, HBO₂ represents a safe and well tolerated treatment modality.¹²

In a recent scoping review of 13 studies including 602 patients, 84% had partial or complete resolution of gross hematuria within 6 to 10 months of completing hyperbaric treatment.⁹ However, 14% experienced recurrence at a median time to relapse of 10 months.⁹ Notably, all but one of these studies were retrospective with relatively short-term follow-up. There remains a lack of prospective randomized control trials evaluating RC HBO₂ bleeding response. Further, longer-term studies demonstrate only around 30% remain in hematuria-free.

The majority of HBO₂ efficacy studies focus on the bleeding outcomes. Few studies have evaluated patient-reported urinary outcomes. Recently, a randomized control trial was performed comparing patient reported urinary outcomes following HBO₂ for RC management compared to usual care.¹³ They found significant improvement in Expanded Prostate Index Composite scores in 41 patients receiving HBOT compared to 38 controls. They excluded more severe cases of RC including those requiring blood transfusions withing 4 weeks of HBO₂ initiation, needing indwelling catheters, and having urinary fistulae. Current data on RC HBO₂ outcomes are promising but are generally limited by heterogeneous cohorts (ranging from mild to severe RC) and the unpredictable time course of RC symptom development. Importantly, while HBO₂ for RC is associated with fewer bladder bleeding events and reduced lower urinary tract symptoms in some patients, little is understood about HBO₂’s underlying mechanism, optimum timing of treatment initiation, or treatment duration.

To address this knowledge gap, the International Multicenter Registry for Hyperbaric Oxygen Therapy (under the registered identifier DERR1-10.2196/18857), supported by the Undersea and Hyperbaric Medical Society was established in 2011.¹² This consortium includes 26 centers regularly entering clinical and patient-reported data on a variety of HBO₂ indications, including RC. At present, there are over 400 patients in the registry with a diagnosis of RC. This consortium offers a means to pool data, increase study power, and prospectively collect data on RC HBO₂ outcomes. Findings from this cohort will be used to improve our understanding of HBO₂ efficacy and will contribute to further understanding outcomes and improve pelvic cancer survivorship.