ANAHEIM, Calif. -- Injection of botulinum toxin A directly into the prostate provided relief from refractory benign prostatic hypertrophy symptoms for up to a year, found a small study in Taiwan.
ANAHEIM, Calif., May 25 -- Injection of botulinum toxin A directly into the prostate provided relief from symptoms of refractory benign prostatic hypertrophy for up to a year, according to a small study.
Three-fourths of patients had at least 30% improvement in urinary symptoms and quality of life, found Yao-Chi Chuang, M.D., of Chang Gung University in Taiwan.
In some cases the improvement persisted for as long as a year, he said at the American Urological Association meeting here. No patient reported any major side effects.
"The results are encouraging because they indicate that Botox could represent a simple, safe, and effective treatment for enlarged prostate that has long-term benefits," commented University of Pittsburgh urologist Michael Chancellor, M.D., an investigator in the study.
Dr. Chuang reported results of a study involving 37 patients with a history of BPH that had responded inadequately to medical therapy. The men had moderate or severe urinary tract symptoms, as reflected by a score of eight or higher on the International Prostate Symptom Scale (IPSS). The patients had a peak urinary flow of less than 12 ml/sec, and all had symptoms that were refractory to medical treatment.
Treatment consisted of single injection session of botulinum toxin A in saline solution. The dose was determined by a patient's prostate volume. Those with a prostate volume of 30 ml or less (n=20) received 100 U administered in divided doses into both lobes of the prostate. Men whose prostate volume exceeded 30 ml (n=17) received 200 U of botulinum toxin administered by two injections into each lobe.
Outcome measures were change in IPSS score, quality of life index (0-6), peak urinary flow (Qmax), post-void residual urine volume, and prostate volume. Follow-up visits occurred one, three, and six months after treatment.
Dr. Chuang said 27 of the 37 men in the study had at least 30% improvement in both the IPSS and quality of life index. At six and 12 months, the average prostate volume had decreased by about 15% in both dose groups.
However, six patients in the 100-U group and five in the 200-U group had no change in prostate volume, the presumed mechanism of action of botulinum toxin A in the prostate. Nonetheless, six of those 11 patients had at least 30% improvement in symptom and quality of life scores.
"The percentage of prostate volume change did not correlate with percentage change in Qmax, lower urinary tract symptoms, or quality of life," said Dr. Chuang.
"The mechanisms of relief of lower urinary tract symptoms through intraprostatic botulinum toxin A injection may involve more than volume shrinkage. The inhibitory effect on the smooth muscle tone, inflammatory process, and aberrant sensory function may plan an important role. Placebo-controlled studies with histology and molecular biology evaluation are needed to prove the mechanisms and confirm the beneficial effect of botulinum toxin A in BPH."
Another Taiwanese study evaluated botulinum toxin A as add-on therapy for men who had large prostates and a history of suboptimal response to combination medical therapy for BPH. Prostate volume exceeded 50 mL in all cases, and the patients had received maximal medical therapy consisting of the combination of an alpha-blocker and a 5-alpha reductase inhibitor.
Thirty patients received botulinum toxin A at doses ranging between 200 and 600 U, depending on prostate volume. Their clinical outcomes were compared against those of 30 other BPH patients who remained on combination medical therapy, according to Hann-Chorng Kuo, M.D., of Buddhist Tzu Chi General Hospital in Hualien, Taiwan. Dr. Kuo was not present to discuss his poster presentation.
Among patients treated with botulinum toxin A, mean prostate volume decreased by an average of 23.5%, mean Qmax by 2.9 mL/sec., and mean PSA level by 35.4%. Three patients were judged to have excellent results and 22 had symptomatic improvement.
The remaining five patients were unchanged. As compared to patients who continued medical therapy, the add-on group had greater improvement in IPSS, quality of life, prostate volume, transition zone index, Qmax, and PSA level. Dr. Kuo reported that 83% of the botulinum toxin A group expressed satisfaction with their treatment compared to 17% of patients who received only combination medical therapy.
The results from the two studies did not meet with universal acceptance. Vanderbilt University urologist Roger Dmochowski, M.D., echoed the sentiments of Dr. Chancellor, particularly with respect to the durability of the symptom relief. On the other hand, Claus Roehrborn, M.D., of the Univeresity of Texas Southwestern Medical Center in Dallas, expressed some reservations about the complete absence of patients with symptom worsening after botulinum toxin injection.
"Are you sure you didn't have a single patient who had a worsening of the symptom score or the flow rate or the quality of life score? Not a single patient?" Dr. Roehrborn asked Dr. Chuang.
Dr. Chuang affirmed that none of his patients had symptom deterioration after the injection therapy.
A 10-patient dose-finding study provided additional evidence that botulinum toxin A might have a role in the treatment of benign prostate hypertrophy and lower urinary tract symptoms. Patients with moderate to severe lower urinary tract symptoms received doses of 100 to 200 U by way of transrectal injection into the prostate and were followed for six months.
Of nine patients who completed follow up, six had significant improvement in the AUA Symptom Scale and peak flow rate; however, four of the six patients had a relapse to baseline symptoms by six months, reported Al Barqawi, M.D., of the University of Colorado in Denver.
Five patients had a significant reduction in prostate volume. No patient developed dose-limiting toxicity, but two patients had episodes of hematospermia, which proved to be self-limiting. Dr. Barqawi noted that a phase II randomized trial is underway to determine the clinical efficacy of botulinum toxin A in a large cohort of patients with benign prostate hypertrophy and lower urinary tract symptoms in the U.S.