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A Preliminary Study on the Impact of Detrusor Overactivity on the Efficacy of Selective Bladder Denervation for the Treatment of Female Refractory Overactive Bladder - Beyond the Abstract

Overactive bladder (OAB) is a syndrome and as such may have one or more etiologies. Several hypotheses have been proposed to explain the pathophysiology and etiology of OAB and detrusor overactivity (DO)1 which are largely centered around the neurogenic and myogenic etiologies, but to date, it is not clear which of these explains most of the available data.2,3 While OAB is a symptomatic diagnosis, DO is a urodynamic finding. Many patients with OAB do not have DO though most patients with DO do indeed have symptoms of OAB. It is not clear why this disparity should exist.4

Turner-Warwick5 coined the term “the bladder is an unreliable witness” meaning that lower urinary tract symptoms do not always yield the underlying diagnosis, but rather this could be determined by urodynamics (UDS). Later, it was posited that video UDS was the gold standard for the diagnosis of lower urinary tract pathology.6,7 However, subsequently it was shown that office UDS had poor sensitivity for the diagnosis of DO8 calling into question the supremacy of UDS investigations.

Another approach to solving this conundrum was to examine the response to therapy. In an elegant experiment, Malone-Lee’s group carried out pretreatment UDS on all patients with OAB and then randomized them to treatment with an antimuscarinic agent or placebo. Treatment was shown to be superior to placebo, but the outcomes were found to be independent of DO status suggesting that a symptom-based approach in this uncomplicated set of OAB patients was sufficient and that UDS was not needed prior to a therapeutic trial.9

Not all patients respond to behavior modification or oral therapy for OAB. The latter leads to poor persistency whereby approximately 70% to 90% discontinue therapy after one year either due to lack of efficacy or tolerability.10 There is, therefore, a large and growing number of refractory OAB patients who need third-line therapy and the vast majority of these are women. To the best of our knowledge, it is not known if the success of treatment in this population of refractory OAB can be predicted by DO status. It is for this reason that we carried our recently published study.11

Selective Bladder Denervation (SBD) is a novel therapy in women using radiofrequency energy to ablate subtrigonal tissue containing a high density of afferent nerves. The rationale of this procedure was based on the increasingly well-accepted concept that increased bladder afferent signaling results in OAB symptoms and of the pioneering work of Ingelman-Sundberg who first interrupted bladder pelvic innervation in refractory OAB patients through an invasive surgical procedure that included extirpation of the inferior hypogastric ganglion.12 This procedure was subsequently modified to be less extensive to spare the hypogastric ganglion13 and it did result in good long-term results.14 However, through concerns of a rebound phenomenon in terms of symptoms and also the sometimes difficult dissection required, this procedure has fallen out of favor. The innovation of SBD has allowed such denervation to be possible by a minimally invasive approach. Its feasibility was initially demonstrated in sheep15 and subsequently shown in women with refractory OAB to be efficacious and durable up to one year.16

Recent literature put forward the concept that OAB is the result of a multifactorial pathology and hence, treatments should be tailored to patient characteristics rather than using a linear treatment algorithm with a “one size fits all” approach.1 The objective of our preliminary study was to test this concept and to determine if the presence or absence of baseline DO could predict the outcomes of SBD in refractory OAB female patients. We first hypothesized that patients without DO (DO-) would respond better to the afferent nerve ablation than patients exhibiting DO (DO+) on UDS.

Our results11 demonstrated that SBD significantly alleviated several OAB symptoms among the 23 refractory OAB female patients of our cohort. Clinical success (≥ 50% reduction in urgency incontinence) was maintained throughout the entire one-year follow-up in 60% of DO- patients and 92% of DO+ patients. Patients with and without DO also reported subjective improvement at the 12-week and 12-month follow-up. Both groups benefited similarly from the procedure as no statistically significant difference was found in comparing the objective and subjective outcomes. Interestingly, repeated UDS at the 12-week follow-up showed that 6 out of the 13 DO+ patients at baseline became DO- (46%) and only one out of the 10 DO- patients converted to DO+ (10%). Although these results were not statistically significant in our small sample size and may represent the limited reproducibility of UDS rather than the effect of SBD, this finding may be worthy of further investigations.

UDS studies are usually recommended prior to initiating third-line treatments for refractory OAB.17 Our results suggest that their role prior to SBD may not be necessary as all patients improved comparably regardless of pretreatment DO status. A larger randomized controlled trial is necessary to confirm our findings. Whether our conclusion can be generalized to all 3rd line therapies remains to be elucidated.

Written by: Raphaëlle Brière, Faculty of Medicine, Université Laval, Québec, Canada; Eboo Versi, MD, PhD, Department of Obstetrics, Gynecology, Reproductive Sciences, Rutgers, New Brunswick, United States; and Le Mai Tu, MD, Division of Urology, Department of Surgery, Faculty of Medicine and Health Sciences, Centre Hospitalier Universitaire de Sherbrooke and Centre de Recherche du CHUS, Canada

References:

  1. Peyronnet, Benoit, Emma Mironska, Christopher Chapple, Linda Cardozo, Matthias Oelke, Roger Dmochowski, Gérard Amarenco et al. "A comprehensive review of overactive bladder pathophysiology: on the way to tailored treatment." European urology (2019).
  2. Drake, Marcus J., Anthony Kanai, Dominika A. Bijos, Youko Ikeda, Irina Zabbarova, Bahareh Vahabi, and Christopher H. Fry. "The potential role of unregulated autonomous bladder micromotions in urinary storage and voiding dysfunction; overactive bladder and detrusor underactivity." BJU international 119, no. 1 (2017): 22-29.
  3. Birder, Lori, and Karl-Erik Andersson. "Urothelial signaling." Physiological reviews 93, no. 2 (2013): 653-680.
  4. Brière, Raphaëlle, Eboo Versi, Patrick O. Richard, and Matthieu Gratton. "A preliminary study on the impact of detrusor overactivity on the efficacy of selective bladder denervation for the treatment of female refractory overactive bladder." Urology (2019).
  5. 5. Bates, C. P., C. G. Whiteside, and Richard Turner‐Warwick. "Synchronous cine/pressure/flow/cysto‐urethrography with special reference to stress and urge incontinence." British Journal of Urology 42, no. 6 (1970): 714-723.
  6. Versi E, Cardozo LD. Urodynamics. In "Progress in Obstetrics and Gynaecology" Ed JWW Studd, Churchill Livingstone. 1990;8:193 218.
  7. VERSI, EBOO, LINDA CARDOZO, DINA ANAND, and DEREK COOPER. "Symptoms analysis for the diagnosis of genuine stress incontinence." BJOG: An International Journal of Obstetrics & Gynaecology 98, no. 8 (1991): 815-819.
  8. Colli, Enrico, Walter Artibani, John Goka, Fabio Parazzini, and Alan J. Wein. "Are urodynamic tests useful tools for the initial conservative management of non-neurogenic urinary incontinence? A review of the literature." European urology 43, no. 1 (2003): 63-69.
  9. Malone‐Lee, J., D. J. E. Henshaw, and K. Cummings. "Urodynamic verification of an overactive bladder is not a prerequisite for antimuscarinic treatment response." BJU international 92, no. 4 (2003): 415-417.
  10. Wagg, Adrian, Gerhard Compion, Amanda Fahey, and Emad Siddiqui. "Persistence with prescribed antimuscarinic therapy for overactive bladder: a UK experience." BJU international 110, no. 11 (2012): 1767-1774.
  11. Brière, Raphaëlle, Eboo Versi, Patrick O. Richard, and Matthieu Gratton. "A preliminary study on the impact of detrusor overactivity on the efficacy of selective bladder denervation for the treatment of female refractory overactive bladder." Urology (2019).
  12. Ingelman‐Sundberg, Axel. "Partial denervation of the bladder: A new operation for the treatment of urge incontinence and similar conditions in women." Acta obstetricia et gynecologica Scandinavica 38, no. 4 (1959): 487-502.
  13. Cespedes, R. Duane, Cindy A. Cross, and Edward J. McGuire. "Modified Ingelman-Sundberg bladder denervation procedure for intractable urge incontinence." The Journal of urology 156, no. 5 (1996): 1744-1747.
  14. Westney, O. Lenaine, Justin T. Lee, Edward J. Mcguire, J. Lynn Palmer, R. Duane Cespedes, and Cindy L. Amundsen. "Long-term results of Ingelman-Sundberg denervation procedure for urge incontinence refractory to medical therapy." The Journal of urology 168, no. 3 (2002): 1044-1047.
  15. Fugett, James, Lynette Phillips, Emily Tobin, Eric Whitbrook, Haydon Bennett, Joshua Shrout, and James E. Coad. "Selective bladder denervation for overactive bladder (OAB) syndrome: From concept to healing outcomes using the ovine model." Neurourology and urodynamics 37, no. 7 (2018): 2097-2105.
  16. Rovner, Eric S., Eboo Versi, Tu Le Mai, Roger R. Dmochowski, and Stefan De Wachter. "One‐year results with selective bladder denervation in women with refractory overactive bladder." Neurourology and urodynamics 38, no. 8 (2019): 2178-2184.
  17. Gormley, E. Ann, Deborah J. Lightner, Kathryn L. Burgio, Toby C. Chai, J. Quentin Clemens, Daniel J. Culkin, Anurag Kumar Das et al. "Diagnosis and treatment of overactive bladder (non-neurogenic) in adults: AUA/SUFU guideline." The Journal of urology 188, no. 6S (2012): 2455-2463.
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