Low-energy extracorporeal shock-wave therapy with or without intravesical botulinum toxin A instillations for refractory interstitial cystitis/bladder pain syndrome: a randomized double-blind trial of clinical and biomarker outcomes.

[PURPOSE] Intravesical botulinum toxin A (BoNT-A) injection effectively alleviates symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS) but remains invasive. Low-energy shock-wave therapy (LESW) has emerged as a novel, noninvasive alternative. This study investigated whether LESW could enhance BoNT-A penetration through the urothelium and improve therapeutic outcomes in patients with refractory IC/BPS.

[METHODS] In this prospective, randomized, double-blind trial, 51 adults with refractory IC/BPS received four weekly suprapubic LESW sessions. Patients were then catheterized and instilled with either 100 U BoNT-A in 30 mL saline (LESW + BoNT-A, n = 25) or saline alone (LESW + NS, n = 26). The primary endpoint was the 4-week change in O'Leary-Sant symptom score (OSS). Secondary endpoints included pain visual analog scale (VAS), voiding diary parameters, urodynamic results, global response assessment, urinary biomarker levels, and safety during 8 weeks. The results for the total cohort, the LESW + BoNT-A group, and the LESW + NS group were reported separately.

[RESULTS] Across the cohort, LESW, with or without BoNT-A, significantly reduced IC problem index and pain VAS at week 1, maintaining VAS improvement to week 8. LESW + BoNT-A induced only transient ICPI reduction, whereas LESW + NS further improved OSS, voided volume, and nocturia. BoNT-A instillation after LESW offered no advantage over saline. Urinary eotaxin and prostaglandin E₂ increased after BoNT-A, while 8-isoprostane decreased after saline. No urinary retention, hematuria or infection occurred in both groups.

[CONCLUSION] LESW alone provides safe, short-term symptomatic relief for refractory IC/BPS. BoNT-A 100U weekly intravesical instillation after LESW modifies urinary biomarkers but lacks of additional clinical efficacy.