Botulinum toxin shows equivocal results in BPH

October 15, 2005

Scottsdale, AZ--Injecting botulinum toxin A (Botox) into the prostate gland shows potential for providing a quick, easy, and safe treatment option for men with lower urinary tract symptoms related to BPH, but two small studies—one from the United States and Chile, and one from Italy—provided equivocal results regarding the efficacy of this investigational approach. While the Italian data showed significant decreases in International Prostate Symptom Score and prostate size with botulinum toxin, U.S. researchers were unable to duplicate these results. Both studies were presented at the AUA annual meeting in San Antonio.

Scottsdale, AZ-Injecting botulinum toxin A (Botox) into the prostate gland shows potential for providing a quick, easy, and safe treatment option for men with lower urinary tract symptoms related to BPH, but two small studies-one from the United States and Chile, and one from Italy-provided equivocal results regarding the efficacy of this investigational approach. While the Italian data showed significant decreases in International Prostate Symptom Score and prostate size with botulinum toxin, U.S. researchers were unable to duplicate these results. Both studies were presented at the AUA annual meeting in San Antonio.

U.S. researchers tested their 10-minute, ultrasound-guided technique in a two-part study. The procedure uses a 22-gauge needle for the injections and requires no anesthesia. In the first part of the study, 10 patients were injected with botulinum toxin, 100 units, to assess safety, IPSS, flow rates, and bother scores. In the second part, 30 patients received 200 units of botulinum toxin or normal saline in a sham-controlled, double-blind study, and sequential MRIs were taken pretreatment and at 1 and 3 months post-treatment to measure prostate volume.

In the 10-patient group, IPSS dropped from a mean of 21.2 before treatment to 9.7 at 7 months. Although IPSS also declined in the 30-patient group (from 23 to 14), this reduction was similar to that seen in the sham (saline) group. Peak flow rates showed no changes in either group, and MRIs were unable to demonstrate any change in prostate size.

"This is a treatment that is fast, easy, and the patients tolerate it well. If it works, it would be a wonderful treatment," Dr. Larson said. "A longer study with more patients is important."

European data

Dr. Larson also presented data on behalf of Federico Guercini, MD, of Universit�i Perugia, Rome, who led a multicenter study of 16 patients with large-volume prostates (>80 grams) with severe hyperplasia. All received intraprostatic injections of botulinum toxin, 300 units, using a transperineal approach. All patients also underwent a deep prostatic massage following the procedure.

Mean IPSS dropped from 24 at baseline to 9 at 6 months (p=.002). Mean prostate weight, as measured on ultrasound, declined from 106 grams to 53 grams (p=.000), and PSA levels dropped accordingly. Peak flow rates improved from a mean of 8.2 at baseline to 18.1 at 6 months. No complications were reported.

Four patients (25%) in the Italian study required a second botulinum toxin treatment at 2 to 3 months due to lack of effect.

Research should continue

The conflicting data raise questions about the efficacy and durability of intraprostatic botulinum toxin injections in men with LUTS associated with BPH, Dr. Larson said, but he recommended that research continue because of the potential benefit of botulinum toxin and the procedure's safety, tolerability, and simplicity.

In a related development, researchers from the University of Pittsburgh and Chang Gung Memorial Hospital in Taiwan have elucidated the mechanism for botulinum toxin A in an animal model of BPH. The researchers injected varying doses of the agent into the enlarged prostates of adult male rats. One week after injection, two types of altered cellular dynamics were observed-an increase in apoptosis and inhibition of cell proliferation-as was down-regulation of adrenergic receptors in the prostate. Adrenergic receptors cause the contraction of the prostate and bladder muscles, making it difficult to void.

By blocking these receptors, the muscles relax, allowing urine to flow more freely, said co-author Michael Chancellor, MD, of the University of Pittsburgh School of Medicine, who reported the findings at the International Continence Society annual meeting in Montreal.