Response to tibial and sacral nerve modulation in overactive bladder: Is there any correlation?

OBJECTIVES: To assess the correlation between the response to transcutaneous tibial nerve stimulation (TTNS) and subsequent response to sacral nerve modulation (SNM) to treat overactive bladder (OAB). MATERIALS AND METHODS: All patients who consecutively received TTNS followed by a two-stage SNM between January 2016 and June 2022 to treat OAB in two university hospital centers were included. The response to each therapy was evaluated with success defined by a 50% or greater improvement in one or more bothersome urinary symptoms from baseline. The primary endpoint was the statistical relationship between the response to TTNS and the response to SNM, assessed by logistic regression. Secondary endpoints were the statistical relationship between the response to TTNS and the response to SNM when controlling for gender, age (<57 years vs. >57 years), presence of an underlying neurological disease, and presence of DO, adding the factor and interaction to the previous regression model. RESULTS: Among the 92 patients enrolled in the study, 68 of them were women (73.9%), and the median age was 57.0 [41.0-69.0] years. The success was reported in 22 patients (23.9%) under TTNS and 66 patients (71.7%) during the SNM test phase. There was no statistical correlation between response to TTNS and response to SNM in the overall population (confidence interval: 95% [0.48-4.47], p = 0.51). Similarly, there was no statistical correlation when controlling for age <57 years or ≥57 years, with p = 1.0 and p = 0.69, respectively. No statistical study could be conducted for the other subpopulations due to small sample sizes. CONCLUSION: The response to TTNS does not predict the response to SNM in the treatment of OAB. TTNS and SNM should be considered as separate therapies, and the decision-making process for OAB treatment should take this into account.

Development of a predictive tool for sacral nerve modulation implantation in the treatment of non-obstructive urinary retention and/or slow urinary stream: a study from the Neuro-Urology Committee of the French Association of Urology.

PURPOSE: This study aimed to seek predictive factors and develop a predictive tool for sacral nerve modulation (SNM) implantation in patients with non-obstructive urinary retention and/or slow urinary stream (NOUR/SS). METHODS: This study was designed as a retrospective study including all patients who have undergone a two-stage SNM for NOUR/SS between 2000 and 2021 in 11 academic hospitals. The primary outcome was defined as the implantation rate. Secondary outcomes included changes in bladder emptying parameters. Univariate and multivariable logistic regression analysis were performed and determined odds ratio for IPG implantation to build a predictive tool. The performance of the multivariable model discrimination was evaluated using the c-statistics and an internal validation was performed using bootstrap resampling. RESULTS: Of the 357 patients included, 210 (58.8%) were finally implanted. After multivariable logistic regression, 4 predictive factors were found, including age (≤ 52 yo; OR = 3.31 CI95% [1.79; 6.14]), gender (female; OR = 2.62 CI95% [1.39; 4.92]), maximal urethral closure pressure (≥ 70 cmH2O; OR: 2.36 CI95% [1.17; 4.74]), and the absence of an underlying neurological disease affecting the lower motor neuron (OR = 2.25 CI95% [1.07; 4.76]). Combining these factors, we established 16 response profiles with distinct IPG implantation rates, ranging from 8.7 to 81.5%. Internal validation found a good discrimination value (c-statistic, 0.724; 95% CI 0.660-0.789) with a low optimism bias (0.013). This allowed us to develop a predictive tool ( https://predictivetool.wixsite.com/void ). CONCLUSION: The present study identified 4 predictive factors, allowing to develop a predictive tool for SNM implantation in NOUR/SS patients, that may help in guiding therapeutic decision-making. External validation of the tool is warranted.

Five-year Results from the Prospective, Multicenter, Observational SOUNDS Study of Patients with Overactive Bladder Treated with the InterStim System for Sacral Neuromodulation.

BACKGROUND: Although sacral neuromodulation (SNM) for overactive bladder (OAB) is an established therapy, there is a lack of high-quality, long-term data on real-life practice. OBJECTIVE: To report on real-life therapeutic effectiveness, quality of life (QoL), disease severity, and safety as well as patient-reported symptom bother after approximately 5 yr of follow-up. DESIGN, SETTING, AND PARTICIPANTS: A total of 291 OAB patients were enrolled at 25 French sites according to local standard of care. Sacral neuromOdUlation with InterStim therapy for intractable lower uriNary tract DySfunctions (SOUNDS) enrolled both de novo and replacement patients, and a total of 229 patients were permanently implanted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Over the course of the study, patients were followed up six times with two follow-ups in the year after implantation and annually thereafter. Of the patients, 154 completed the final follow-up after a mean of 57.7 ± 3.9 mo. RESULTS AND LIMITATIONS: The mean number of daily leaks in urinary urge incontinence (UI) patients was reduced from 4.4 ± 3.3 at baseline to 1.8 ± 2.6 after 5 yr in de novo and from 5.4 ± 4.9 to 2.2 ± 3.0 in replacement patients (both p < 0.001). Likewise, the number of voids in urinary frequency patients was reduced compared with baseline (de novo: reduced from 12.6 ± 4.0 [baseline] to 9.6 ± 4.3 [5 yr]; replacements: reduced from 11.5 ± 4.3 [baseline] to 9.2 ± 3.1 [5 yr]; both p < 0.05). Complete continence rates after 5 yr were 44% (25/57) in de novo and 33% (5/15) in replacement UI patients, and 68% (39/57) and 67% (10/15) of UI patients were categorized as therapy responders by showing a >50% improvement in leaks. Disease severity (Urinary Symptom Profile domain 2), Numeric Rating Scale-based symptom bother, and disease-specific QoL (Ditrovie) improved significantly in both groups at all visits (p < 0.001). Adverse events related to device or procedure occurred in 51% (140/274) of patients, with 66% (152/229) of the events being classified as minor (Clavien-Dindo grade I and II). Surgical revisions were reported in 39% (89/229), which include permanent explants in 15% (34/229) of patients. CONCLUSIONS: SOUNDS demonstrates the sustained effectiveness and QoL improvements of SNM in OAB patients after 5 yr in real-world conditions while maintaining an acceptable safety profile consistent with literature. PATIENT SUMMARY: This study confirmed that French overactive bladder patients had a sustained symptom and bother reduction, and improvements in quality of life up to 5 yr after sacral neuromodulation device implantation.

Sacral Neuromodulation with the InterStim System for Overactive Bladder: 3-Year Results from the French Prospective, Multicenter, Observational SOUNDS Study.

BACKGROUND: SOUNDS strengthens the evidence basis of sacral neuromodulation (SNM) for overactive bladder (OAB) through real-world data. OBJECTIVE: To analyze diary-based effectiveness, quality of life (QoL), disease severity, symptom bother, and safety data for SNM with the InterStim system up to 3 yr after implantation. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five representative French sites enrolled 291 patients with OAB followed according to the local standard of care. Overall, 229 patients received a de novo or replacement InterStim implant and had four follow-up visits, two within the first yr and annually thereafter. A total of 190 patients completed the fourth follow-up visit after a mean of 33.7 ± 3.7 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The effectiveness outcomes measured were changes in daily voids and leaks and the therapy responder rates. Other outcomes included validated QoL data (Ditrovie and EuroQol 5-dimension 5-level questionnaires), disease severity (Urinary Symptom Profile [USP]), symptom bother rated using a numeric rating scale (NRS), and safety data. Follow-up data were compared to baseline results using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Average daily voids and leaks were significantly reduced at all time points up to 3 yr after implantation (p < 0.05) except for voids at 21 mo in the group receiving a replacement device. The therapeutic response for urinary urge incontinence at the fourth follow-up was 72% for the de novo group and 86% for the replacement group. Disease-specific QoL (Ditrovie), OAB-specific symptom severity (USP domain 2), and NRS-rated disease bother were significantly improved at all visits (p < 0.001). Device- or procedure-related adverse events occurred in 49% of patients, with 68% of the events classified as minor (Clavien-Dindo grade I or II). Surgical revisions were performed in 33% of patients, including permanent removal in 13%, over a mean exposure time of 44.4 ± 15.3 mo. CONCLUSIONS: This study confirms the safety and effectiveness of SNM for OAB and improvements in QoL and disease bother in real life. PATIENT SUMMARY: Our study in French patients with overactive bladder showed that disease symptoms and bother were significantly reduced and quality of life was significantly improved over a study duration of approximately 3 yr after implantation of a device to stimulate nerves that control the bladder. This trial is registered at ClinicalTrials.gov as NCT02186041.

Randomized clinical trials assessing third-line therapies to treat non-neurogenic overactive bladder syndrome: a review about methodology.

INTRODUCTION AND HYPOTHESIS: Using similar methodologies and outcome measures is crucial to allow pertinent literature reviews and meta-analyses. Therefore, this scoping review aims to compare methodologies of randomized clinical trials (RCTs) assessing the efficacy of third-line therapies to treat non-neurogenic OAB: intradetrusor onabotulinumtoxinA (BoNTA) injections, sacral neuromodulation (SNM) and posterior tibial nerve stimulation (PTNS). METHODS: A literature search was conducted using the PubMed search database. Using filters, the search was limited to RCTs conducted on humans and written in English or French since 2000 which evaluated BoNTA injections, SNM and/or PTNS. RCTs focusing on pediatric or neurogenic OAB were excluded. For each included RCT, methodology was assessed using a standardized form investigating the study design, clinical outcomes and urodynamic outcomes. Inclusion criteria, sex ratio, blinding strategies, treatment arms, primary outcomes and delays for reevaluation were assessed. Availability of clinical and urodynamic outcomes was reported at baseline, 3 months and 6 months. RESULTS: Thirty-one RCTs were included in the final synthesis. The most frequent main outcome measure was change in the number of urinary incontinence episodes in 35.5% and in the number of voids per day in 25.8%. Bladder diaries were lacking in 12.9%, 32.3% and 80.1% at baseline, 3 and 6 months, respectively, while 26% of studies reported the results of urodynamic studies at any point. CONCLUSION: Heterogeneity in study designs and data collection was pointed out between RCTs assessing the efficacy of third-line therapies to treat non-neurogenic OAB. We therefore advocate for the development of specific research guidelines focusing on OAB-related therapies.

Sacral Neuromodulation with the InterStim™ System for Intractable Lower Urinary Tract Dysfunctions (SOUNDS): Results of Clinical Effectiveness, Quality of Life, Patient-Reported Outcomes and Safety in a French Multicenter Observational Study.

BACKGROUND: Real-world data that support the use of sacral neuromodulation (SNM) for lower urinary tract dysfunctions are of continued interest. OBJECTIVE: To evaluate the effectiveness, quality of life (QoL), patient-reported outcomes (PROs), and safety of SNM with the InterStim™ system in real life during 1-yr postimplant. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective, multicenter, observational study at 25 representative public and private French sites. Eligible patients received SNM therapy for overactive bladder (OAB) and non-obstructive urinary retention based on local standard of care. Overall, 320 patients were enrolled; 247 received permanent implant or replacement; 204 implanted patients completed second follow-up after mean of 10.0±3.8 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Effectiveness outcomes were change in voids, leaks, and catheterizations/day. Other outcomes included validated QoL and disease severity scores as well as PROs and adverse event data. Outcomes at follow-ups were compared with baseline using the Wilcoxon signed-rank test. RESULTS AND LIMITATIONS: Voids in urinary frequency (UF) and leaks/day in urinary urge incontinence (UI) patients were significantly reduced after 10 mo in both de novo (mean baseline voids/day UF de novo: 12.7 vs 8.6 after 10 mo; p<0.001; mean baseline leaks/day UI de novo: 4.3 vs 1.1 after 10 mo; p<0.001) and replacement patients (mean baseline voids/day UF replacement: 11.5 vs 7.9 after 10 mo; p<0.001; mean baseline leaks/day UI replacement: 5.4 vs 1.0 after 10 mo; p<0.001). Disease bother, Urinary Symptom Profile score, and Ditrovie questionnaire score were also significantly improved. Revisions postimplant occurred in 20% of patients including in 9% due to permanent explantation during a mean exposure time of 24.3 mo. CONCLUSIONS: Through a real-life study, SOUNDS (Sacral neuromOdUlation with InterStim™ therapy for intractable lower uriNary tract DySfunctions) confirms the clinical effectiveness, safety, and positive effect of SNM on QoL and PROs for the treatment of OAB patients. PATIENT SUMMARY: These analyses on French patients who received sacral neuromodulation (SNM) for retention or OAB during a 10-mo period showed that SNM improved OAB symptoms, quality of life, and reduced disease bother. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02186041.