3498 - Low-Dose Radiotherapy for Interstitial Cystitis

Purpose/Objective(s): Interstitial cystitis (aka, painful bladder syndrome, IC/PBS) is characterized by chronic bladder pain, urgency, and frequency without an identifiable infection or other clear cause. The exact etiology is unclear, but it may involve bladder lining defects, immune dysfunction, or nerve hypersensitivity. IC/PBS is estimated to affect 3-7% of women and 1-2% of men in the US. Treatment is individualized and often involves a multimodal approach. No single therapy is universally effective and up to half of affected patients experience inadequate symptom relief. Cats similarly develop feline interstitial cystitis (FIC) and 5- 21% of affected cats are euthanized due to recurrent FIC. Improved therapies are needed for IC/PBS and FIC, and studies in cats may provide valuable translational insight. Because radiotherapy (RT) can have potent anti-inflammatory and neuromodulatory effects, it was hypothesized that low-dose RT could reduce clinical signs of FIC.

Materials/Methods: An IACUC-approved, single-arm, single-institution, prospective clinical trial was conducted to evaluate the clinical effects of irradiating the entire lower urinary tract with a single 6 Gy fraction. Initially, 15 male cats with severe disease and historical urethral obstructions were enrolled, treated, and monitored. Subsequently, the study was opened to 16 female cats.

Results: Of the 15 males, one was immediately lost to follow-up and one died of an unrelated cause at 516 days post-RT. The median follow-up time for all 14 male cats with available follow-up data is 598 days. All but one experienced symptomatic improvement. Six have experienced a single flare-up of FIC signs at a median of 274 days post-RT (range 4 to 395 days). One had a flare-up at 5 months, was retreated (6 Gy x 1), and remains asymptomatic 540 days later. Another had a flare-up at 11 months that was managed surgically. The other 4 male cats with post-RT flare-ups were managed medically and have had no additional problems since. Of the 16 females treated since June 2024, 13 have available follow-up data with a median follow-up time of 51 days. Four of the females have experienced modest improvement and 9 have had persistent or worsening FIC signs resulting in one having been euthanized 26 days after RT.

Conclusion: Low dose radiotherapy appears to be a safe and effective treatment for FIC in male cats with a >90% response rate in this study population. There does however appear to be a sex difference, as early experiences in female cats indicate that only about 1 in 3 female cats respond favorably to a single 6 Gy fraction. Further investigation is required to determine whether protocol modification might benefit female cats, and this should be addressed before attempting to translate results to humans with IC/PBS.