RECONSTRUCTIVE UROLOGY

Botulinum Toxin Injections for Neurogenic and Idiopathic Detrusor Overactivity: A Critical Analysis of Results
Patel AK, Patterson JM, Chapple CR
Sheffield Teaching Hospitals NHS Trust, Urology Research Department, Royal Hallamshire Hospital, Sheffield, United Kingdom
Eur Urol. 2006; 50: 684-709; discussion 709-10

• Objective: In recent years there has been an increasing use of the botulinum neurotoxins for the management of conditions characterised by detrusor overactivity. Early studies showed promising results in an area where few options previously existed between pharmacotherapy and surgery. This has led to an urgent need to assess the wide range of techniques and therapies available, as well as the efficacy and tolerability of the treatment. We performed a critical analysis of the numerous clinical studies for this novel treatment option in the management of neurogenic and idiopathic detrusor overactivity, with a view to directing further research and assisting urologists in the management of these conditions.
• Methods: A systematic review of the literature, as well as a search for abstracts presented to relevant peer-reviewed meetings, was performed. All articles from 1988 onwards were included, prior to which no articles describing urologic use of botulinum neurotoxins had been published, although the majority of the articles have been published since 2000.
• Results and Conclusions: Although many of the studies were small, overwhelming evidence supports the efficacy, safety, and tolerability of the botulinum toxins, specifically serotype A, for the management of these conditions. Before this is accepted as a widespread treatment modality, good-quality evidence from large-scale randomised controlled trials is needed. These studies should identify not only the most appropriate patients to treat but also the best dose, administration technique, and frequency for treatment.
  
  
• Editorial Comment
  The use of botulinum toxin in the treatment of both idiopathic detrusor overactivity (IDO) and neurogenic detrusor overactivity (NDO) is well-established clinical practice. However, as it is not an approved treatment option its use still is off label.
  Schurch et al. were the first to describe the potential of botulinum toxin in the field of urology (1). In their pioneering work they were able to show botulinum toxin to be an effective, minimally invasive approach in the treatment of detrusor sphincter dyssenergy.
  Two recent papers by Schulte-Baukloh et al. and by Patel et al. respectively provide the most comprehensive overview of the state of the art of the field.
  Schulte-Baukloh also includes a critical assessment of Capsaicin and Resiniferatoxin (RTX) as possible alternatives to botulinum toxin. However, both drugs will probably play no more than minor roles in future long-term treatments, especially due to their limited availability as released drugs.
  Patel gives the most complete overview to date of all published studies on the different types of botulinum toxin.
  Both papers assess, summarize and highlight the treatment effectiveness of botulinum toxin over the past 18 years. However, emphasis must again be drawn to the fact that botulinum toxin is still unlicensed and therefore off label in the field of urology.
  All studies on botulinum toxin to date have found overwhelming evidence of its efficacy, safety and tolerability. Even more, its use has demonstrably led to significant improvements in the patients’ quality of life - an aspect often overlooked or forgotten. On top of that, it should be noted that NOB major surgeries, in particular, can be avoided or at least be delayed through use of botulinum toxin.
  Despite of all this positive evidence a lack of worldwide, multi-center, double blind, placebo-controlled clinical trials inhibits the use of botulinum toxin from being more generally accepted. Only 3 placebo-controlled studies (2 on NDO, 1 on IDO) are mentioned by Patel attesting to the urgent need of carrying out accordingly designed studies.
  Consequentially, several such trials have been initiated or are under way right now. Until they will have been completed the drug should primarily be used at designated centers to increase our understanding of its properties and applications.
  Comparison of the different types of botolinum toxin is difficult because of variations in their individual molecular structures and mechanisms of action. The precise mechanism underlying the effects on smooth muscle cells and the nervous system is still not fully understood - as opposed to the well-studied effect guiding the onset of action in the striated muscle - opening further fields of study.

References
1. Schurch B, Hauri D, Largo M, Kreienbuhl B, Meyer E, Rossier AB: Effects of botulinum A toxin on the periurethral striated sphincter of the neurogenic bladder. Preliminary study. J Urol. 1990; 96: 375-80.

K.D. Sievert, B. Winter, A. Stenzl
Department of Urology
Eberhard-Karls-University Tuebingen
Tuebingen, Germany