Jhang JF. et al., 2025: 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.

Jia-Fong Jhang, Hann-Chorng Kuo
Int Urol Nephrol. 2025 Dec 15. doi: 10.1007/s11255-025-04950-z

Abstract

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.

Comment Jens Rassweiler

This study aimed to evaluate the effectiveness of low-energy extracorporeal shock-wave therapy (LESW) alone and in combination with intravesical botulinum toxin A (BoNT-A) for treating patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS). While BoNT-A is known to alleviate symptoms, it is an invasive procedure. LESW is a non-invasive alternative that might enhance the effectiveness of BoNT-A by improving its penetration through the urothelium.

Methods

In this randomized, double-blind trial involving 51 adults with refractory IC/BPS, participants received four weekly sessions of suprapubic LESW. They were then given either 100 U of BoNT-A in 30 mL saline (LESW + BoNT-A, n=25) or saline alone (LESW + NS, n=26). The primary outcome was the change in O’Leary–Sant symptom score (OSS) after four weeks. Secondary outcomes included pain levels (VAS), voiding diary results, urodynamic parameters, and urinary biomarker levels.

Results 

1. Symptom Relief: Both treatment groups showed significant reductions in bladder pain and symptom indices at week one, with improvements maintained to week eight. However, the LESW + NS group exhibited better long-term improvements in OSS, voided volume, and nocturia compared to the LESW + BoNT-A group.

2. Biomarkers: Urinary levels of eotaxin and prostaglandin E₂ increased after BoNT-A treatment, while 8-isoprostane levels decreased after saline instillation. Despite some changes in urinary biomarkers, no significant clinical advantage was noted from the addition of BoNT-A.

3. Safety: No serious adverse events, such as urinary retention or infections, were reported in either group.

Conclusion

LESW alone provides safe and effective short-term relief for patients with refractory IC/BPS. The addition of intravesical BoNT-A did not demonstrate superior clinical efficacy compared to saline alone despite some changes in urinary biomarkers. The study suggests that while LESW is beneficial, the current dosage of BoNT-A may not be sufficient to achieve significant therapeutic advantages. Future research should explore various doses and the potential for longer-term outcomes in larger, multicenter trials.

Discussion

The findings suggest that low-energy extracorporeal shock-wave therapy (LESW) alone can provide significant symptomatic relief for patients with refractory IC/BPS, potentially reducing the necessity for intravesical botulinum toxin A (BoNT-A) injections. The following key-points regarding the potential impact of this study on treatment approaches might be interesting:

1. Reduced Invasiveness: LESW is a non-invasive treatment option, which may be more appealing to patients compared to the invasive nature of BoNT-A injections. This could lead to increased acceptance and adherence to treatment.

2. Symptomatic Relief: The study demonstrated that LESW significantly improved pain and symptom scores, suggesting that it could be an effective standalone treatment for many patients who may otherwise consider more invasive therapies.

3. Cost and Resource Implications: If LESW proves to be effective for a larger group of patients, it may reduce the overall healthcare costs associated with managing IC/BPS, as BoNT-A injections can be expensive and may require multiple treatments.

4. Further Research Needed: While the study indicates that LESW alone can be effective, further research is necessary to understand the long-term efficacy of LESW, the optimal number of sessions, and the specific patient populations that might benefit most. Additionally, exploring various doses of BoNT-A could provide insights into whether it still holds value in conjunction with LESW for certain patients. Herein, the combination with extracorporeal magnetotransduction (EMTT) therapy using the Magnetolith should be also considered.

In conclusion, while LESW appears to be a promising alternative that might reduce or eliminate the need for BoNT-A in some patients, ongoing research and clinical evaluation will be crucial to fully understand its role in the management of IC/BPS.

Jens Rassweiler