Refractory Overactive Bladder in Men

1. Refractory Overactive Bladder in Men Kristy M. Borawski, MD Associate Professor Department of Urology University of North Carolina @BorawskiKristy

2. Overall prevalence of OAB is significant • EPIC study • 11.8% with OAB • NICE study • 18-64 y/o: 3% urinary incontinence • >65: 8.5% • 28.5% of these with clinically significant urge urinary incontinence Irwin, et al. Eur Urol 2006; 50:1306-1314. Morant SV, et al. Int J ClinPract 2008; 62:688-694

3. Overall prevalence of OAB is significant • Stewart, et al. US based study • 16% prevalence of OAB in men • OAB wet symptoms increase with age with substantial increases after age 64 • Lower Urinary Tract Dysfunction Research Network (LURN) • 51% of responders reported any urinary incontinence • 46% urge incontinence • Older patients with higher odds of nocturia & urgency Stewart, et al. World J Urol 2003; 20(6):327-336. Cameron, et al. J Urol 2018; 199(4):1023-1031.

4. Coyne KS, et al. Urol 2011; 77(5): 1081-1087.

5. Economic Impact $76.2 billion in 2015 Coyne KS, et al. J Manag Care Pharm 2014; 20(2):130-140.

6. $0.24/pad, 3 per day $21.60/month $259 / year $0.24/pad, 6 per day $43.20/month $518 / year

7. Avg Social SecutityMonthy Benefit: $1461 4% of monthly income on depends $0.68/brief, 3 per day $61/month $734 / year

8. Are we ignoring male OAB? • Morant et al • 25% men diagnosed with OAB • 6-7% of men with storage LUTS were placed on anticholinergics • 36% of men with LUTS/BPH received alpha blocker and/or 5-alpha reductase inhibitor Morant, et al. Int J ClinPract 2008; 62:688-694.

9. Pathophysiology of OAB in men Hormonal changes Bladder outlet obstruction Aging Ischemia Neurologic conditions Gomelsky, et al. TherAdv Urol 2009; 1(4):209-221.

10. Nadir Osman and Christopher Chapple. Bladder outlet obstruction and the overactive bladder. In Overactive Bladder: Practical Management. 2015.

11. Will OAB symptoms improve after treatment of bladder outlet obstruction?

12. Will OAB symptoms improve after treatment of BOO? • Symptomatic OAB persists in ~25-30% of patients post TURP • UK: 10 year follow-up post TURP • Increase in detrusor overactivity from 40-60% in those who remain unobstructed Nadir Osman and Christopher Chapple. Bladder outlet obstruction and the overactive bladder. In Overactive Bladder: Practical Management. 2015.. Thomas AW. J Urol 2005 174: 1887-1891.

13. Will OAB symptoms improve after treatment of BOO? • Persistent OAB symptoms associated with: • Advanced age • Lower maximum cystometric capacity • Early onset detrusor overactivity • High amplitude detrusor overactive contraction Antunes et al. J Urol 2015; 193: 2028-2032. Nadir Osman and Christopher Chapple. Bladder outlet obstruction and the overactive bladder. In Overactive Bladder: Practical Management. 2015.

14. Management for male refractory OAB f

15. Weight Modification

16. 8% weight loss resulted in a 70% reduction in all incontinence episodes (both stress and urge incontinence) NEJM 360, 2009.

17. Combination medical therapy f

18. Combination therapySolifenacin + mirabegron Mueller, et al. Neurol Urodyn 2019; 38: 779-792.

19. Solifenacin 5mg + mirabegron 50mg • Combination group with greater improvement over monotherapy • Incontinence episodes / 24 hr • Micturitions / 24 hr Mueller, et al. Neurol Urodyn 2019; 38: 779-792.

20. Solifenacin 5mg + mirabegron 50mgSafety • 47.2% all patients reported at least one adverse event • Higher incidence in combination group • Increase in mean pulse rates from baseline of >1bpm were noted in combination & mirabegron group only in younger age groups • Blood pressure: all three groups had minor increase in systolic blood pressure • No clinically significant change in combination group compared to monotherapy groups Mueller, et al. Neurol Urodyn 2019; 38: 779-792.

21. Solifenacin 5mg + mirabegron 50mgSafety • Increased residual urine volume • No patients in mirabegron group had increased PVR • No patients in solifenacin group had increased PVR • 3/1206 had increased PVR in combination group • No data on gender available • Age: 2 were <75 y/o Mueller, et al. Neurol Urodyn 2019; 38: 779-792.

22. Solifenacin 5mg + mirabegron 50mgSafety • Urinary retention • Mirabegron: 1 (0.3%) patient >65 y/o • Solifenacin: 1 (0.3%) patient <65 y/o • Combination group: 6 (0.5%) patients all <75 • No data on gender available Mueller, et al. Neurol Urodyn 2019; 38: 779-792.

24. OnabotulinumtoxinA

25. OnabotulinumtoxinA

27. Placebo vsOnabotA 100U • 60% vs 29% positive response • 5.4% retention rate • 350+ = CIC • 200-350mL based on symptoms • 88.4% female

28. Placebo vsOnabotulinumA 100 U • Similar outcomes to EMBARK study • 6.9% CIC • PVR >350mL = CIC • PVR 200-350mL based on symptoms • 84.5% female

29. 92% female Placebo vsOnabotA 50U/100U/150U/200U/300U

30. Male subjects >18 years of age with confirmed detrusor overactivity on urodynamics who received intradetrusorBoNT-A from 2004 – present • 65 men received 133 BoNT-A treatments • 6 had prior BOO procedure • 9 had prior prostatectomy • 100 units most common dose in men Urology 2018; 123: 242-246.

31. Faure Walker et al. Urol 2018; 123: 242-246.

32. CIC recommended for PVR >150mL with symptoms Faure Walker et al. Urol 2018; 123: 242-246.

33. Baseline urodynamics in men Men with good bladder contractility (BCI >150) had lower de novo CIC but did not reach significance BCI = PdetQMax + (5 x Qmax) Faure Walker et al. Urol 2019; 123: 242-246.

34. 88 male patients with mean follow up of 69 months • Success defined as patient still on treatment at last follow-up or stopped botox treatment due to cure of symptoms Neurol Urodyn 2017; 36: 1855 – 1859.

36. 75% of patients stopped treatment due to either insufficient results or side effects

37. Side effects • 5% required de novo CIC • PVR >250mL • 12.5% UTI

38. Randomized, double-blind, placebo controlled pilot study of intradetrusor injections of onabotulinumtoxinA for the treatment of refractory overactive bladder persisting following surgical management of benign prostatic hyperplasia. Chughtai B1, Dunphy C, Lee R, Lee D, Sheth S, Marks L, Kaplan SA, Te AE. Can J Urol 2014; 2: 7217 – 7221. 2 center double blinded RCT in patients with OAB secondary to BOO refractory or anticholinergic medication & persistent >3 months after surgical intervention for BOO Placebo vs 200U onabotulinumtoxinA

39. Randomized, double-blind, placebo controlled pilot study of intradetrusor injections of onabotulinumtoxinA for the treatment of refractory overactive bladder persisting following surgical management of benign prostatic hyperplasia. Chughtai B1, Dunphy C, Lee R, Lee D, Sheth S, Marks L, Kaplan SA, Te AE. • OnabotulinumtoxinA group with improved QOL scores at 180 & 270 days after treatment • Lower ICIQ (incontinence questionnaire) scores • Decreased urinary frequency (11 8/day) although statistical significance not achieved • IPSS, PVR & urgency were unchanged postoperatively in both groups

40. Electrical Stimulation

41. Sacral Nerve Stimulation

42. Sacral Nerve Stimulation Success rates 33-88% at 6 months widely reported for refractory urge incontinence

44. Neurourol Urodyn 2015; 24: 224-230.

45. J Urol 2018; 199: 229-236.

46. J Urol 2018; 199: 229-236.

47. J Urol 2018; 199: 229-236.

48. J Urol 2018; 199: 229-236.

49. Does Gender Influence Response Rates to Sacral Neuromodulation? Less men undergo placement of impulse generator (IPG) compared to women Anger, et al. 2016. Outcomes of SNM in a privately insured population Laudano et al. 2015. Disparities in the use of SNM among Medicare beneficiaries Cameron, et al. 2011. National trends in the usage of sacral nerve test stimulation

50. 92% women vs. 82% men had initial success & went onto placement of generator • Men • More overall improvement in urge incontinence episodes per day • Less incontinence severity • Although improvement in incontinence severity only seen in women • Similar QOL parameters Int Urol Neph 2018; 50: 825-832.