Bad Prostate Leading to Urinary Cather Use? -Botox Might Fix It

I have one desperate case where a good 85 year old was up all night peeing from inability to empty bladder. He had a heart attack less than a year prior and urology consult wasn’t well received.  Put 100 u botox into each side of prostate and now he gets up every 3 hours. A study has shown it can get old men off urine catheters.

BMC Urol. 2009 Aug 15;9:9.
Intraprostatic Botulinum Toxin Type A injection in patients with benign prostatic enlargement: duration of the effect of a single treatment.
Silva J, Pinto R, Carvalho T, Botelho F, Silva P, Oliveira R, Silva C, Cruz F, Dinis P. free article here

And (published it in 2 places)

European urology 53 ( 2 0 0 8 ) 153–159
Intraprostatic Botulinum Toxin Type A Injection in Patients Unfit for Surgery Presenting with Refractory Urinary Retention and Benign Prostatic Enlargement. Effect on Prostate Volume and Micturition Resumption
Joa˜ o Silva a,b, Carlos Silva a,b,c, Luis Saraiva a,b, Andre´ Silva a,b, Rui Pinto a,Paulo Dinis a,b,c, Francisco Cru  abstract here

• age 80 +/- 2 years
• Twenty-one men with benign prostatic enlargement on chronic indwelling catheter for at least 3 mo who were not candidates for surgery because of poor general condition
• 200 units into transition zone
• “swiftly reduced prostatic volume”
• At 1 mo, 16 patients (76%) could resume voiding with a mean Qmax of 9.0+/-1.2 ml/s
• They used Cipro coverage – 500 mg before and bid for 5 days

Similar results in another study:

Urology Volume 65, Issue 4 , Pages 670-674, April 2005
Prostate botulinum A toxin injection—an alternative treatment for benign prostatic obstruction in poor surgical candidates
Hann-Chorng Kuo  abstract here

• Ten patients with BPH and urinary retention or a large postvoid residual urine volume
• 200 U botulinum A toxin injection into the transition zone of the prostate –
• 8 had an excellent result (80%) and 2 had an improved result

Another found that 100 units total botox might be enough:
The Journal of Urology Volume 186, Issue 3 , Pages 965-970, September 2011
Effects of 100 and 300 Units of Onabotulinum Toxin A on Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: A Phase II Randomized Clinical Trial
E. David Crawford, Kathryn Hirst et al  abstract here

• Over 50 years old with poor flow rates but less than 350 mls post void residual
• 100 units worked as well as 300 units

What about compared to placebo?

Urology. 2003 Aug;62(2):259-64; discussion 264-5.
Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study.
Maria G, Brisinda G, Civello IM, Bentivoglio AR, Sganga G, Albanese A. abstract here              free article here

• 30 cases )15 each group)
• 200 units Botox in 4 mls
• “After 2 months, 13 patients in the treated group and 3 in the control group had subjective symptomatic relief (P = 0.0007).”
• 65% improvement in symptom scores versus no significant change in placebo
• They found it “safe, effective, and well-tolerated”

What are long term results?

Urology. 2009 Jan;73(1):90-4. Epub 2008 Nov 8.
Relief by botulinum toxin of lower urinary tract symptoms owing to benign prostatic hyperplasia: early and long-term results.
Brisinda G, Cadeddu F, Vanella S, Mazzeo P, Marniga G, Maria G.    abstract here

• 77 men with BPH [benigh prostatic hypertrophy]
• 200 intraprostatic BT A units (Botox) using an ultrasound-guided transperineal approach
• 1 month – prostatic volume and residual urine volume were reduced by 12.7% and 12.8%, respectively
• 2 months – prostatic volume, and residual urine volume were reduced by 51.6% (P = .00001), 42.8% (P = .00001), and 55.9% (P = .002)

One study still found benefit at 6 months but not 12:

Scand J Urol Nephrol. 2009;43(3):206-11
Therapeutic effects of add-on botulinum toxin A on patients with large benign prostatic hyperplasia and unsatisfactory response to combined medical therapy.
Kuo HC, Liu HT.  abstract here

• “This study shows that add-on prostatic BoNT-A medical treatment can reduce prostate volume and improve lower urinary tract symptom score and QoL-I within 6 months in the treatment of large BPH. However, the therapeutic effect at 12 months was similar to combination medical treatment.”

It does appear conditions revert to baseline at 18 months (Silva above)

Does it effect erectile function? – No

It seems to help that if it improved voiding (God, there going to be selling this stuff on street corners…)

Yonsei Med J. 2006 Oct 31;47(5):706-14.
Evaluation of short term clinical effects and presumptive mechanism of botulinum toxin type A as a treatment modality of benign prostatic hyperplasia.
Park DS, Cho TW, Lee YK, Lee YT, Hong YK, Jang WK.   free article here

• “Additionally, about 50 percent of the patients whose voiding symptom improved expressed improved erectile function”

One study looking specifically at whether it could make things worse:
Intraprostatic botulinum toxin type A administration: evaluation of the effects on sexual function
João Silva1, Rui Pinto1, Tiago Carvalho1, Francisco Botelho1, Pedro Silva1, Carlos Silva1,2,3, Francisco Cruz1,2,3,*, Paulo Dinis
BJU International Volume 107, Issue 12, pages 1950–1954, June 2011   abstract here

• 200 units used in 16 sexually active men over 60 yr old with prostatism
• Conclusion “does not impair erectile, orgasmic or ejaculatory functions and does not change libido.”

How’s it work?

Apparently it induces some cellualr “apoptosis” = death and shrinks (atrophy) the prostate that way:
Intraprostatic injection of botulinum toxin type- A relieves bladder outlet obstruction in human and induces prostate apoptosis in dogs
Yao-Chi Chuang1, Chieh-Hsien Tu2, Chao-Cheng Huang3, Hsin-Ju Lin2, Po-Hui Chiang1, Naoki Yoshimura4 and Michael B Chancellor*
BMC Urology 2006, 6:12 doi:10.1186/1471-2490-6-12  free article here

• . It also alters the sympathetic nervous tissue.EUROPEAN UROLOGY 5 6 ( 2 0 0 9 ) 1 3 4 – 1 4 1
  Mechanisms of Prostate Atrophy after Glandular Botulinum Neurotoxin Type A Injection: An Experimental Study in the Rat
  Joa˜o Silva a, Rui Pinto a, Tiago Carvallho a, Ana Coelho b, Antonio Avelino b,c,
  Paulo Dinis a,b,c, Francisco Cruz   free article here
• It also  downregulaties α-1A-adrenoreceptors:

Curr Opin Urol. 2011 Jan;21(1):13-21.
Botulinum neurotoxin A for male lower urinary tract symptoms.
Chartier-Kastler E, Mehnert U, Denys P, Giuliano F.  abtract here

• It has anticholinergic effects and alters Nitrous Oxide in tissues:
  Yonsei Med J. 2006 October 31; 47(5): 706–714.
  Evaluation of Short Term Clinical Effects and Presumptive Mechanism of Botulinum Toxin Type A as a Treatment Modality of Benign Prostatic Hyperplasia
  Dong Soo Park, Taek Woo Cho, Yong Kyu Lee, Young Tae Lee, Young Kwon Hong, and Woong Ki Jang  free article here
• It effects autonomic nervous system and relaxes prostate

My Technique (version 1.0)

I do not have transrectal ultrasound but am used to doing piriformis injections so can do  transperineal injection with finger in rectum.

• Have patient lie on right side facing away, buttocks over edge and knees up
• left index finger in rectum on prostate (backwards from usual approach to rectal exams) and right hand injecting in perineum (between rectum and testicle). I put some local in but there seems to be very little feeling in this area so probably not necessary.
• I just enter somewhat infront of anus to right of midline and injected to one side into right lobe prostate first – you can feel needle tugging through tissues.. When it reaches prostate it is actually softer going in. Then go to left of midline and tract toward prostate on left side. I couldn’t do “transition zone” precision but patient got better anyway.
• I used 1 ml solution each side but see they have used up to 2 mls a side
• I am a strong believer in the inadequacy of “one shot wonders”, and suspect shot would need to be repeated in 6 – 12 months – and in 6 wks (I do not wait 3 months for fear of developing botox resistance), if results were inadequate initially.
• I had patient take cipro 500 mg before procedure and bid for 5 days but this might be unnecessary ( suspect it was the transrectal ones that used antibiotics – similarly to after a prostate biopsy)
• It looks like 50 units botox each side of prostate might do – meaning $400.00 treatment

Having only done one, I could use other people’s experience! – please comment…

The idea of people now left on urinary catheters seems like an unnecessarily  hardship.  However, with long term obstruction, the bladder will become a large poorly contractile enlarged bag structure, that might need it…

 addendum

One case used in in presence of prostate cancer:
Vezdrevanis, Konstantinos.
Prostatic carcinoma shrunk after intraprostatic injection of botulinum toxin.
Urology journal 8.3 (2011): 239-241.
http://journals.sbmu.ac.ir/urolj/index.php/uj/article/download/1140/594

• 68 year old with fast growing prostate cancer (gleason 8)
• castration-refractory one year after the primary diagnosis
• using 100 units dysport ( about 250 u botox) in 7 mls injected under ultrasound “between the two apparent hypoechoic areas”.
• lead to rapid decrease in prostate size
• felt this could be particularly useful in “obstruction refractory to medical treatment and unwilling to undergo transurethral resection of the prostate [or not suitable] “