3.2.2. Hyperbaric Oxygen Therapy (HBOT)

This technique consists of placing the patient in a pressurized chamber (hyperbaric chamber) to administer pure or mixed oxygen at a pressure greater than atmospheric pressure, for 5–7 days a week, for a daily duration of 60–90 min up to approximately 30–45 sessions [27]. The effect of hyperbaric oxygen therapy is to allow better oxygen diffusion in tissues and to disrupt the continuum between hypoxia and fibrosis. Hyperoxia induces primary neovascularization, secondary growth of healthy granulation tissue, and induces short-term vasoconstriction, which may help control active bleeding [28,29]. It is the most widely reported therapeutic technique in the management of hemorrhagic radiation cystitis. Dellis et al. evaluated the benefit of HBOT in 38 patients with severe radiation cystitis. The complete response rate was 86.8%, and the partial response rate was 13.2%. The mean follow-up was 29.3 months. For the thirty-three patients with complete response who received HBO therapy within 6 months of the hematuria onset, the mean time interval was 4.9 months (range 1–6), while in the remaining five patients with partial response, the mean time interval was 22 months (range 8–48) (*p* < 0.001). Thirty-three patients were alive at the end of follow-up [29].

Recently, the randomized phase 2–3 RICH-ART evaluated the benefit of HBOT compared to standard of care for patients with late radiation cystitis and a value of fewerthan 80 points in the urinary domain of the expanded prostate index composite score (EPIC score). Forty-one patients were randomized in the HBOT arm and 38 in the standard of care arm. HBOT significantly alleviated patient-perceived symptoms of late radiation cystitis and improved HRQOL. The mean improvement in EPIC urinary total score was higher (17.8 [SD 18.4]) in the hyperbaric oxygen therapy group compared with patients in the control group (7.7 [SD 15.5]). Seventy patients in HBOT presented a grade 1–2 adverse events. The main adverse events grade 1–2 were ear pain (15%), myopia (12%) and barotrauma (10%). No grade 3–4 or 5 was reported in this group [30]. The HBOT's benefit was maintained in the time. In fact, Pereira et al. reviewed 105 patients diagnosed with RIHC whowere treated with HBOT between 2007 and 2016. After a median follow-up of 63 months, 76.3% had a complete response [31]. Cardinal et al. evaluated the benefits of HBOT through a meta-analysis of data from 602 patients treated with HBOT for hemorrhagic radiation cystitis. They determined that 84% of patients achieved partial or complete resolution, while 75% saw an improvement in hematuria. In their analysis of 499 patients with documented follow-up, authors observed a recurrence rate of 14%, with a median time to recurrence of 10 months (6 to 16.5 months). To summarize, this treatment is well-tolerated, the most common side effects being pressure-related, most notably ear and sinus barotrauma. HBOT is offered to patients for whom bladder washings and instillations are ineffective [32]. In a systemic review, Villeirs et al. emphasized HBOT benefit in radiation cystitis. In a cohort of 815 patients, an overall and complete response rate varied from 64.8% to 100% and 20% to 100%, respectively. Blood transfusion before HBOT, other treatment modalities before HBOT, use of anticoagulant therapy, along the interval between the onset of hematuria and start of HBOT were possible factors associated with lower efficacy of HBOT [27]. It is important to start HBOT in the onset of late radiation cystitis symptoms [33,34]. However, the availability and cost-effectiveness of high-pressure oxygen tanks is a critical factor in the success of HBOT [27].
