Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study

doi:10.1016/S0090-4295(03)00477-1

Urology

Volume 62, Issue 2, August 2003, Pages 259-264

https://doi.org/10.1016/S0090-4295(03)00477-1 Get rights and content

Abstract

Objectives

To evaluate the therapeutic role of botulinum toxin injection in men with benign prostatic hyperplasia.

Methods

Men with benign prostatic hyperplasia were enrolled in a randomized, placebo-controlled study. After a baseline evaluation, each participant received 4 mL of solution injected into the prostate gland. Patients in the control group received saline solution and patients in the treated group received 200 U of botulinum toxin A. The outcome of each group was evaluated by comparing the symptom scores, serum prostate-specific antigen concentration, prostate volume, postvoid residual urine volume, and peak urinary flow rates.

Results

Thirty consecutive patients were enrolled. No local complications or systemic side effects were observed in any patient. After 2 months, 13 patients in the treated group and 3 in the control group had subjective symptomatic relief (P = 0.0007). In patients who received botulinum toxin, the symptom score was reduced by 65% compared with baseline values and the serum prostate-specific antigen concentration by 51% from baseline. In patients who received saline, the symptom score and serum prostate-specific antigen concentration were not significantly changed compared with the baseline values and 1-month values. Follow-up averaged 19.6 ± 3.8 months.

Conclusions

Botulinum toxin injected into the prostate seems to be a promising approach for the treatment of benign prostatic hyperplasia. It is safe, effective, and well-tolerated. Furthermore, it is not related to the patient’s willingness to complete treatment.

Section snippets

Material and methods

The study was conducted at Department of Surgery of the University Hospital Agostino Gemelli, Rome. The institutional review board approved the protocol for this double-blind, placebo-controlled study.

Results

Forty-two consecutive outpatients were assessed for eligibility. Of them, 8 patients did not meet the inclusion criteria and 4 patients refused to participate. Thus, 30 patients were randomized: 15 received BT and 15 placebo. No differences were found at baseline between the two groups (Table I). No complications during the procedure were observed in any patient.

Comment

BPH management is currently in transition.4, 5, 7 Although surgery will continue to be widely used, medical therapies are assuming increasing importance, owing to the desire of patients to avoid surgery whenever possible. A pilot study on the impact of a program to aid in decision-making about BPH showed a 40% decrease in the surgery rate in American patients.24 However, the goal of therapy is to relieve lower urinary tract symptoms. For this reason, the efficacy of any treatment for

Conclusions

We found BT injection into the prostate to be a promising approach to the treatment of BPH. It is well-tolerated and should be considered for patients who are at risk of surgery. Furthermore, it is not related to the patient’s willingness to complete treatment. Additional investigation of BT treatment is indicated before its general use can be advocated.

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Use of botulinum toxin A in pelvic floor dysfunctions in the elderly: A review
2019, Progres en Urologie
Le présent article constitue le rapport de la réunion de travail multi-disciplinaire organisée par le GRAPPPA (groupe de recherche appliquée à la pathologie pelvi-périnéale des personnes âgées). L’objectif est de dresser une synthèse de l’utilisation de la toxine botulinique A (TBA) dans la prise en charge des troubles pelvi-périnéaux du sujet âgé.
Le présent article a été construit comme une revue compréhensive de la littérature, associant données issues de la littérature scientifique et avis d’experts. La revue systématique de la littérature a été menée à partir de la base de données bibliographique MedLine (National Library of Medicine). Concernant les injections intra-détrusoriennes de TBA, seuls les articles rapportant des résultats spécifiques chez les sujets âgés (> 65 ans) étaient inclus. Concernant les autres localisations, compte-tenu du nombre restreint de données, tous les articles rapportant les résultats de la TBA étaient systématiquement inclus, quelle que soient la population étudiée. En cas de données manquantes ou insuffisantes, des avis d’expert étaient formulés.
Bien que les données issues de cette population spécifique soient limitées, il semble que la TBA pourrait être proposée chez le sujet âgé sans critère de fragilité dans la prise en charge de l’HAV, avec taux de succès comparable aux patients jeunes à 3 mois (88,9 % vs 91,2 %), 6 mois (49,4 % vs 52,1 %) et 12 mois (23,1 % vs 22,3 %), et une diminution significative du nombre de mictions quotidiennes (11,4 vs 5,29 p < 0,001) et du nombre de protections quotidiennes (4,0 vs 1,3, p < 0,01). Elle pourrait par ailleurs bientôt être proposée dans la prise en charge de la dyschésie ano-rectale et de l’IF. En revanche, elle ne peut actuellement être recommandée dans la prise en charge de l’obstruction sous-vésicale.
La TBA présente un intérêt dans la prise en charge de divers troubles pelvi-périnéaux du sujet âgé, et ses différentes applications devraient être mieux évaluées au sein de cette population spécifique tant en termes de sécurité que d’efficacité.
The present article is the final report of a multi-disciplinary meeting supported by the GRAPPPA (group for research applied to pelvic floor dysfunctions in the elderly). The objective was to conduct a comprehensive review on the role of botulinum toxin A (BonTA) in the treatment of pelvic floor dysfunctions in the elderly.
The present article, written as a comprehensive review of the literature, combines data issued from the scientific literature with expert's opinions. Review of the literature was performed using the online bibliographic database MedLine (National Library of Medicine). Regarding intra-detrusor BonTA injections, only articles focusing on elderly patients (> 65 yo) were included. Regarding other localizations, given the limited number of data, all articles reporting outcomes of BonTA were included, regardless of studies population age. In case of missing or insufficient data, expert's opinions were formulated.
Although, available data are lacking in this specific population, it appears that BonTA could be used in the non-fraily elderly patients to treat overactive bladder or even neurogenic detrusor overactivity, with a success rate comparable to younger population at 3 months (88.9% vs. 91.2%), 6 months (49.4% vs. 52.1%) and 12 months (23.1% vs. 22.3%), as well as a significant decrease in number of voids per day (11.4 vs. 5.29 P < 0.001) and in the number of pads per day (4.0 vs. 1.3, P < 0.01). Furthermore, BonTA is likely to be offered in the future as a treatment of fecal incontinence and obstructed defecation syndrome symptoms. Concerning bladder outlet obstruction/voiding dysfunction symptoms, intra-urethral sphincter BonTA should not be recommended.
BonTA injections are of interest in the management of various pelvic floor dysfunctions in the elderly, and its various applications should be better evaluated in this specific population in order to further determine its safety and efficacy.
Surgical Management of LUTS/BPH: New Mini-Invasive Techniques
2018, Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia: From Research to Bedside
In the setting of benign prostatic obstruction related to hyperplasia, novel treatment strategies based on new mini-invasive techniques are currently in development. UroLift implants are the most developed and are recommended by most international Guidelines. Prostatic arterial embolization is currently being evaluated and is still experimental. Finally, botulinic toxin prostatic injections have been thoroughly tested, but phase 3 studies did not show any beneficial effects.
Botulinum toxin and benign prostatic hyperplasia
2018, Asian Journal of Urology
Benign prostatic hyperplasia (BPH) is a clinical condition where lower urinary tract symptoms are caused by both a physically obstructing prostate as well as tight smooth muscles around the bladder outlet. Treatment of this condition with botulinum toxin has been used since 2003, but this interest has somewhat died down after two large randomized controlled trials (RCTs) showing equivalence of results between their treatment and placebo arms. However, with review of animal studies and unexplained exaggerated effect of the placebo arms of the two RCTs, together with recent data of sustained benefits after 18 months of treatment, the place of botulinum toxin in the BPH field is probably still present.
Emerging Minimally Invasive Treatment Options for Male Lower Urinary Tract Symptoms[Figure presented]
2017, European Urology
Lower urinary tract symptoms (LUTS) are one of the most common and troublesome nonmalignant conditions affecting quality of life in aging men. A spectrum of established medical and surgical options is available to provide relief of bothersome LUTS. Both the adverse events of medication and the morbidity with surgical treatment modalities have to be counterbalanced against efficacy. Novel minimally invasive treatment options aim to be effective, ideally to be performed in an ambulatory setting under local anaesthesia and to offer a more favourable safety profile than existing reference techniques.
A comprehensive, narrative review of novel minimally invasive treatment modalities for the management of male LUTS due to benign prostatic enlargement is presented.
Medline, PubMed, Cochrane database, and Embase were screened for randomised controlled trials (RCTs), clinical trials, and reviews on novel minimally invasive treatment options for male LUTS due to benign prostatic enlargement.
With regard to newly devised intraprostatic injectables (botulinum neurotoxin A, NX1207, PRX302), PRX302 is currently the only substance that was superior to placebo in a phase 3 RCT providing proof of efficacy and safety. The prostatic urethral lift technique has been evaluated in several phase 3 trials showing rapid and durable relief of LUTS without compromising sexual function in carefully selected patients without a prominent median lobe. The first clinical experience of the temporary implantable nitinol device demonstrated that implantation of this novel device is a safe procedure, easy, and fast to perform. Further studies are required to evaluate efficacy, durability, and to define appropriate patient selection. New ablative approaches like the image guided robotic waterjet ablation (AquaBeam) or procedures based on convective water vapour energy (Rezūm) are in the early stages of development. Prostatic artery embolization performed by interventional radiologists at specialised centres shows a high technical success rate in the treatment of bothersome LUTS. However, a substantial clinical failure rate and a particular spectrum of complications not commonly seen after urologic interventions do occur and need to be critically evaluated.
Initial promising clinical results on novel minimally invasive treatment options indicate efficacy comparable to standard techniques, often associated with a more favourable safety profile, in particular with preservation of sexual function. Many of these techniques are in their infancy and based on experience of new developments in the past. Further RCTs are required to evaluate efficacy, safety, and durability of novel techniques with long-term follow-up and careful evaluation of the selection criteria, which have been applied in clinical trials. The prostatic urethral lift is the only procedure with Level 1 evidence data and that can therefore be recommended for treatment of male LUTS in clinical practice for selected patients.
Minimally invasive treatment options have been developed to provide relief of lower urinary tract symptoms comparable to standard surgical techniques with a more favourable safety profile. However, long-term clinical evaluation is still needed for most of these innovations before they can be recommended to be an effective replacement for standard surgical treatment.
Botulinum toxin A treatment for lower urinary tract symptoms/benign prostatic hyperplasia
2017, Urological Science
Botulinum toxin A (BoNT-A) has been widely used in the treatment of overactive bladder and neurogenic detrusor overactivity. Recently, prostatic injection of BoNT-A had been tried to reduce the prostate volume and relieve lower urinary tract symptoms (LUTS) in patients with benign prostatic enlargement (BPE) due to benign prostatic hyperplasia (BPH). However, the efficacy of BoNT-A on BPE is still controversial. Traditionally, male LUTS have been considered as synonym of BPE because most male LUTS developed in aging men. Recent investigations have revealed that bladder dysfunction and bladder outlet dysfunction other than BPE contribute equally in male LUTS. Injecting BoNT-A into the prostatic urethra and bladder neck yielded improvement of LUTS, but not reduction of the prostatic volume, especially in men with small prostatic volume. The therapeutic effects of BoNT-A on LUTS might not be due to prostatic volume reduction, but through inhibiting the adrenergic hyperactivity in men with LUTS/BPH. This article discusses the current consensus and controversy of BoNT-A treatment on LUTS/BPH.
A Relevant Midterm (12 Months) Placebo Effect on Lower Urinary Tract Symptoms and Maximum Flow Rate in Male Lower Urinary Tract Symptom and Benign Prostatic Hyperplasia—A Meta-analysis
2017, Urology
To assess the mid- to long-term placebo effect of the medical and instrumental management of male lower urinary tract symptoms. This is generally a long-term treatment strategy. Therefore, knowledge on the mid- to long-term placebo effect is of considerable interest. The paucity of data on this topic prompted us to investigate this issue in a meta-analysis.
All randomized controlled trials (RCTs) with the indication of benign prostatic hyperplasia and lower urinary tract symptoms containing a placebo- or sham treatment arm and with a follow-up of 12 months were eligible. The 12-month effect of placebo or sham treatment on the International Prostate Symptom Score (the quality-of-life question was not analyzed herein) and the American Urological Association Symptom Score and on the maximum flow rate was quantified.
A total of 25 RCTs with 10.587 patients were eligible. Twenty-three studies were placebo controlled (plant extracts: n = 4, 5α-reductase inhibitors [5ARIs]: n = 9, α-blocker: n = 5, combination therapy of 5ARI and α-blocker: n = 3, and intraprostatic botulinum toxin A injection: n = 2), and 2 RCTs with transurethral microwave thermotherapy (TUMT) had a sham treatment arm. At 12 months, the mean International Prostate Symptom Score improved by a mean of 4.4 points under placebo or sham treatment with a range of 0.7-6.8 points: plant extracts, −3.6; 5ARI, −3.4; α-blocker, −4.3; combination therapy, −4.3; botulinum toxin A, −3.9; and TUMT, −6.8. The mean maximum flow rate improvement at 12 months under placebo or sham was not relevant (+0.8 mL/s), yet there were remarkable differences between trials: plant extracts, −0.3 mL/s; 5ARI, +0.8 mL/s; α-blocker, +1.1 mL/s; combination therapy, +1.4 mL/s; and TUMT, +1.0 mL/s.
This meta-analysis demonstrates the mid-term placebo effect on lower urinary tract function, particularly concerning subjective improvement. The degree of the placebo effect varies considerable between studies even at 12 months.

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Adult urologyRelief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study

Abstract

Objectives

Methods

Results

Conclusions

Section snippets

Material and methods

Results

Comment

Conclusions

Urology

Urology

Urology

Urology

Surgery

J Urol

J Urol

Lancet

J Urol

J Urol

J Urol

Urology

J Urol

Urology

Benign prostatic hyperplasiamedical and minimally invasive treatment options

N Engl J Med

Adult urology
Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study