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Mens urological health cme bph-luts- final- nov 13 2013

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Mens urological health cme bph-luts- final- nov 13 2013

  1. 1. 11 CLINICAL PRACTICE Q&A A CME PROGRAM FOR MEN’S UROLOGICAL HEALTH BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS BPH-LUTS HOME
  2. 2. 22 STEERING COMMITTEE Ghalib Ahmed, MD, CCFP General Family Practitioner, Associate Clinical Professor, Department of Family Practice, University of Alberta Gerald Brock, MD, FRCSC Professor of Surgery, Urology Program Director, University of Western Ontario Chair Office of Education, Canadian Urology Association Lydia Hatcher, MD, CCFP, FCFP Clinical Associate, Professor of Family Medicine, Memorial University of Newfoundland Murray Awde, MD, CCFP, FCFP Clinical Professor of Family Medicine, University of Western Ontario Serge Carrier, MD, FRCSC Associate Professor, Division of Urology, Department of Surgery, McGill University Jay Lee, MD, FRCSC Clinical Assistant Professor, Division of Urology, Department of Surgery, University of Calgary Anthony Bella, MD, FRCSC Greta and John Hansen Chair in Men's Health Research, Assistant Professor of Urology, Department of Surgery, Associate Scientist, Neuroscience, University of Ottawa Stacy Elliott, MD Director, BC Center for Sexual Medicine, Sexual Medicine Consultant, Men’s Health Initiative, Vancouver Coastal Health Clinical Professor, Departments of Psychiatry and Urologic Sciences, University of British Columbia BPH-LUTS HOME
  3. 3. 33 STEERING COMMITTEE DISCLOSURES Ghalib Ahmed, MD, CCFP • Grants/Research Support: AstraZeneca, Bristol-Myers Squibb, Pfizer, Servier, Sunovion • Speaker’s Bureau/Honoraria: Abbott, AstraZeneca, Eli Lilly, Lundbeck, Merck, Pfizer, Shire • Consulting Fees: Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Lundbeck, Merck, Pfizer Murray Awde, MD, CCFP, FCFP • Grants/Research Support: Astellas, Bristol-Myers Squibb, Boehringer Ingelheim, Merck, Novartis, Otsuka, Purdue Pharmaceuticals • Speaker’s Bureau/Honoraria: Abbott, AstraZeneca, Bayer, LEO, Takeda, Nycomed • Consulting Fees: Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Novo Nordisk, Pfizer Anthony Bella, MD, FRCSC • Grants/Research Support: Acorda Therapeutics, Canadian Foundation for Innovation, Canadian Male Sexual Health Council, Northeastern Section American Urological Association • Speaker’s Bureau/Honoraria: Abbott, American Medical Systems, Bayer, Coloplast, Eli Lilly, Pfizer Gerald Brock, MD, FRCSC • Grants/Research Support: American Medical Systems, Eli Lilly, GlaxoSmithKline, Pfizer • Speaker’s Bureau/Honoraria: American Medical Systems, Bayer, Coloplast, Eli Lilly, GlaxoSmithKline, Pfizer • Consulting Fees: Bayer, Eli Lilly, GlaxoSmithKline, Pfizer Serge Carrier, MD, FRCSC • Grants/Research Support: Bayer, Eli Lilly, Pfizer • Speaker’s Bureau/Honoraria: Abbott, Bayer, Eli Lilly, Pfizer Stacy Elliott, MD • Speaker’s Bureau/Honoraria: Abbott, Bayer, Eli Lilly, Pfizer • Consulting Fees: Abbott, Bayer, Eli Lilly, Pfizer Lydia Hatcher, MD, CCFP, FCFP • Grants/Research Support: Servier • Speaker’s Bureau/Honoraria: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen-Ortho, Merck, Nycomed, Pfizer, Purdue Pharmaceuticals, Takeda, Valeant • Consulting Fees: AstraZeneca Jay Lee MD, FRCSC • Speaker’s Bureau/Honoraria: Abbott, Bayer, Eli Lilly, GlaxoSmithKline, Pfizer BPH-LUTS HOME
  4. 4. 4 4 SPEAKER DISCLOSURES • Faculty: [Speaker’s name] • • • • Grants/Research Support: Speaker’s Bureau/Honoraria: Consulting Fees: Other: HOME
  5. 5. 5 5 DISCLOSURE OF COMMERCIAL SUPPORT • This program has received financial support from Eli Lilly Canada Inc in the form of an educational grant • This program has received in-kind support from Eli Lilly Canada Inc in the form of logistical support. • Potential for conflict(s) of interest: • [Speaker/Faculty name] has received funding Eli Lilly Canada Inc. • Eli Lilly markets tadalafil, a product that will be discussed in this program. HOME
  6. 6. 6 6 MITIGATING POTENTIAL BIAS • All content in this presentation has been developed, reviewed and approved by the Steering Committee • All the recommendations involving clinical medicine are based on evidence from well-designed clinical trials published in peerreviewed journals HOME
  7. 7. 77 BPH-LUTS • The goal of this module is to address common questions in the area of BPH-LUTS • Benign prostatic hyperplasia is the histological pattern of the prostate, characterized by proliferation of smooth muscle and epithelial cells within the prostatic transition zone. This may lead to prostatic enlargement. • Lower urinary tract symptoms refer to storage and/or voiding disturbances. • BPH-LUTS refers to bothersome lower urinary tract symptoms linked to the prostate BPH: benign prostatic hyperplasia; LUTS: lower urinary tract symptoms. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; 2. Abrams et al. J Urol. 2009; 181:1779-87. BPH-LUTS HOME
  8. 8. 88 BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS 1 How should I evaluate a patient with BPH-LUTS? 3 How do I decide which agent to prescribe for BPH-LUTS? 5 2 Is there evidence of a relationship between BPH-LUTS and ED? 4 When should I refer a patient to a urologist? How should I follow-up with a BPH-LUTS patient? BPH-LUTS HOME
  9. 9. 99 BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS 1 How should I evaluate a patient with BPH-LUTS? BPH-LUTS HOME
  10. 10. 10 10 LEARNING OBJECTIVES • After completing this question participants will be able to: • Identify diagnostic assessments for BPH-LUTS and integrate these into clinical practice • Evaluate the utility of PSA testing and recognize the CUA’s position on testing • Distinguish the signs and symptoms of OAB from BPH-LUTS CUA: Canadian Urological Association; OAB: overactive bladder; PSA: prostate-specific antigen. BPH-LUTS HOME
  11. 11. HOW SHOULD I EVALUATE A PATIENT WITH BPH-LUTS? • • • • • 11 11 Medical history Directed physical exam Urinalysis PSA testing Symptom assessment PSA: prostate-specific antigen. BPH-LUTS HOME
  12. 12. 12 12 MEDICAL HISTORY • Medical history should assess:1,2 • • • • • • Nature and duration of symptoms Fluid intake – amount and types of fluid Comorbid conditions Prior and current illness Prior surgery and trauma Current medications Do you routinely ask about sexual function when evaluating a patient for LUTS? 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Abrams et al. J Urol. 2009;181:1779-87. BPH-LUTS HOME
  13. 13. 13 13 BPH-LUTS AND ED • BPH-LUTS and ED are common comorbid conditions 100 % of Patients with Erectile Problems 90 80 50-59 yrs (n=5,786) 60-69 yrs (n=4,191) 70-79 yrs (n=2,828) 70 60 50 40 30 20 10 0 No symptoms Mild Moderate Severe Severity of LUTS 1. Rosen et al. Eur Urol. 2003;44:637-49. BPH-LUTS HOME
  14. 14. 14 14 DIRECTED PHYSICAL EXAM • Physical examination for patients with BPH-LUTS:1,2 • MANDATORY EVALUATION – DIGITAL RECTAL EXAM • Evaluate prostate for size, consistency, shape and abnormalities suggestive of prostate cancer (such as nodules or asymmetry) • Assess suprapubic area to rule out bladder distention • Evaluate overall motor and sensory function of the perineum and lower limbs especially with a history of stroke or neurologic disease 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Abrams et al. J Urol. 2009;181:1779-87. BPH-LUTS HOME
  15. 15. 15 15 URINALYSIS • Dipstick urinalysis should be performed in all BPH-LUTS patients to rule out other diagnoses that may cause LUTS: Urinalysis Result Possible Diagnosis • Hematuria • Kidney stones • Bladder cancer • Pyuria or presence of nitrates • UTI • Urethral stricture • Proteinuria • Underlying renal disease • Glucosuria • Diabetes Abnormal/borderline urinalysis results should be repeated and/or followed with a urine culture1 UTI: urinary tract infection. 1. Abrams et al. J Urol. 2009;181:1779-87. BPH-LUTS HOME
  16. 16. 16 16 PSA TESTING Do you currently recommend PSA testing for your patients with BPH-LUTS? PSA: prostate-specific antigen. BPH-LUTS HOME
  17. 17. 17 17 WHY PSA TESTING? PSA can Help Predict Prostate Size 75 Prostate Volume (ml) 60 70 65 60 50 55 50 40 30 1 2 3 4 Serum PSA 5 6 7 ng/mL-1 Adapted from Roehrborn et al. Urology. 1999;53:581-9. DRE: digital rectal exam; PSA: prostate-specific antigen. 1. Roehrborn et al. Urology. 1999;53:581-9. BPH-LUTS HOME
  18. 18. PSA CAN IDENTIFY PATIENTS WITH HIGHER RISK OF RETENTION OR SURGICAL INTERVENTION Four Year Incidence (%) 26 18 18 Need for BPH-related surgery Acute urinary retention 24 20 18 14 10 6 2 >0 >1 >2 >3 >4 >5 Baseline PSA Thresholds >6 >7 >8 PSA: prostate-specific antigen. 1. Roehrborn et al. Urology. 1999;53:473-80. BPH-LUTS HOME
  19. 19. 19 19 CUA RECOMMENDATIONS FOR PSA TESTING • The CUA position on PSA as a screening test for prostate cancer DIFFERS from the USPSTF1 • CUA recommends PSA testing be offered to all men ≥50 years of age with a life expectancy of ≥10 years. • Canadian guidelines for the management of BPH-LUTS suggest PSA testing for:2 • Patients who have at least a 10 year life expectancy, and for whom the presence of prostate cancer would change management • Patients for whom PSA measurement may change the management of their voiding symptoms (estimate for prostate volume) CUA: Canadian Urological Association; PSA: prostate-specific antigen; USPSTF: United States Preventive Services Task Force. 1. CUA position statement on PSA testing. November 2011; 2. Nickel et al. CUAJ. 2010;4:310-6. BPH-LUTS HOME
  20. 20. 20 20 SYMPTOM ASSESSMENT • Assess the severity of symptoms and degree of bother1 • Evaluate response to treatment • Validated symptom assessment tools are available: • International Prostate Symptom Score (IPSS) • American Urological Association (AUA) symptom score Click here for more info on IPSS • Lower urinary tract symptoms classified as:2 • Storage symptoms • Voiding symptoms • Post-micturition symptoms 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Abrams et al. Urology. 2003;61:37-49. BPH-LUTS HOME
  21. 21. 21 21 STORAGE (IRRITATIVE) SYMPTOMS Q • • • • • • What are the characteristic storage symptoms? Frequency Nocturia Urgency Urinary incontinence Stress incontinence Urge incontinence 1. Abrams et al. Urology. 2003;61:37-49. BPH-LUTS HOME
  22. 22. 22 22 VOIDING (OBSTRUCTIVE) SYMPTOMS Q • • • • • • What are the characteristic voiding symptoms? Slow stream Splitting or spraying Intermittent stream Hesitancy Straining Terminal dribble 1. Abrams et al. Urology. 2003;61:37-49. BPH-LUTS HOME
  23. 23. 23 23 POST-MICTURITION SYMPTOMS Q What are the characteristic post-micturition symptoms? • Feeling of incomplete emptying • Post-micturition dribble 1. Abrams et al. Urology. 2003;61:37-49. BPH-LUTS HOME
  24. 24. 24 24 SYMPTOM BOTHER LUTS Presentation Mild Symptoms Moderate – Severe Symptoms No Significant Bother Moderate – Severe Bother IPSS Quality of Life Assessment2 “If you were to spend the rest of your life with your urinary condition as is, how would you feel about it?” IPSS: International Prostate Symptom Score. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Barry et al. J Urol. 1992;148:1549-57. BPH-LUTS HOME
  25. 25. 25 25 OPTIONAL ASSESSMENTS • Optional assessments for BPH-LUTS include: • • • • • • Post-void residual Sexual function questionnaire (i.e. SHIM)2 Serum creatinine Urine cytology Uroflow Voiding diary Click here for more info on SHIM SHIM: Sexual Health Inventory for Men. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Rosen et al. Int J Imp Res. 1999;11:319-26. BPH-LUTS HOME
  26. 26. 26 26 OTHER ASSESSMENTS (NOT RECOMMENDED) • Other assessments can be considered, however these are not recommended for BPH-LUTS: • • • • • • Cystoscopy Cytology Urodynamics Radiological evaluation of upper urinary tract (CT/MRI) Prostate ultrasound Prostate biopsy CT: computed tomography; MRI: magnetic resonance imaging. 1. Nickel et al. CUAJ. 2010;4:310-6. BPH-LUTS HOME
  27. 27. 27 27 DISTINGUISHING BPH-LUTS FROM OAB Q How do you distinguish between BPH-LUTS and OAB? Typically distinguished by: • Voiding symptoms • Failure of standard BPH-LUTS therapy to resolve symptoms OAB: overactive bladder. BPH-LUTS HOME
  28. 28. 28 28 BPH-LUTS VS. OAB BPH-LUTS • Prostate-mediated bladder voiding obstruction symptoms • Frequency, nocturia, urgency • Intermittent stream, straining • Weak urinary stream • Sense of incomplete emptying OAB • BPH-LUTS medications fail to resolve storage symptoms • Urgency (+/- urge incontinence) • Frequency, nocturia OAB: overactive bladder. 1. Clemens et al. J Urol. 2007;178:1354-8. BPH-LUTS HOME
  29. 29. PERSISTENT STORAGE SYMPTOMS MAY BE A SIGN OF OTHER PROBLEMS 29 29 WARNING Persistent storage symptoms may be related to other conditions • Higher risk in smokers and patients with microscopic hematuria • Storage symptoms secondary to neurologic disease may be more difficult to treat BPH-LUTS HOME
  30. 30. 30 30 TAKE HOME MESSAGES • Evaluation of BPH-LUTS includes: • Medical history (including comorbid conditions) • BPH-LUTS and ED are common comorbid conditions • Physical exam (with DRE) • Urinalysis • PSA testing • Sensitive marker for prostate volume • Recommended in patients with BPH-LUTS and a life-expectancy >10 years • Symptom bother assessment • OAB is characterized by storage symptoms which persist upon treatment of BPH-LUTS DRE: digital rectal exam; ED: erectile dysfunction; OAB: overactive bladder; PSA: prostate-specific antigen. 1. Nickel et al. CUAJ. 2010;4:310-6. BPH-LUTS HOME
  31. 31. 31 31 BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS 2 Is there evidence of a relationship between BPH-LUTS and ED? BPH-LUTS HOME
  32. 32. 32 32 LEARNING OBJECTIVES • After completing this question participants will be able to: • Recognize the link between BPH-LUTS and ED and its implications for treatment • Assess recent data for PDE5 inhibitors in BPH-LUTS and integrate this new indication into clinical practice PDE: phosphodiesterase. BPH-LUTS HOME
  33. 33. IS THERE EVIDENCE OF A RELATIONSHIP BETWEEN BPH-LUTS AND ED? 33 33 • Epidemiological • Pathophysiological BPH-LUTS HOME
  34. 34. 34 34 EPIDEMIOLOGICAL LINK BETWEEN BPH-LUTS & ED % of Patients with Erection Problems • Erection problems strongly associated with LUTS (p<0.001)1 100 90 80 70 60 50 40 30 20 10 0 50-59 yrs (n=5,786) 60-69 yrs (n=4,191) 70-79 yrs (n=2,828) No symptoms Mild Moderate Severe Severity of LUTS 1. Rosen et al. Eur Urol. 2003;44:637-49. BPH-LUTS HOME
  35. 35. 35 35 CAUSE OF BPH-LUTS • Original thinking was that BPH-LUTS was the result of: • Physical obstruction by the prostate • Contraction of the bladder neck Mechanisms now implicated in BPH-LUTS:1 • Altered smooth muscle relaxation or contractility • Reduced blood flow • Reduced function of nerves and endothelium 1. Gacci et al. Eur Urol. 2011;60:809-25. BPH-LUTS HOME
  36. 36. 36 36 LOCALIZATION OF PDE5: IMPLICATIONS FOR BPH-LUTS • PDE5 enzyme blocks NO mediated smooth muscle relaxation • The PDE5 enzyme is found in tissues of the:1 • • • • Penis Bladder Prostate Urethra PDE5 NO: nitric oxide; PDE5: phosphodiesterase 5. 1. Fibbi et al. J Sex Med. 2010;7:59-69. BPH-LUTS HOME
  37. 37. SMOOTH MUSCLE CONTRACTION: IMPLICATIONS FOR BPH-LUTS 37 • PDE5 inhibitor increases:1 • NO, causing smooth muscle relaxation • Blood flow to the pelvis and penis GMP Smooth muscle relaxation Smooth muscle contraction cGMP cGMP: cyclic guanosine monophosphate: GMP: guanosine monophosphate; NO: nitric oxide; PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor. 1. Wang. Curr Opin Urol. 2010;20:49-54. BPH-LUTS HOME
  38. 38. ALL PDE5 INHIBITORS HAVE BEEN SHOWN TO IMPROVE BPH-LUTS Sildenafil1* 0 Vardenafil2* Weeks 6 12 0 -1 8 0 -1 Mean Change in Symptom Score Mean Change in Symptom Score 0 Weeks 4 38 -2 -3 -4 -5 -6 Placebo Sildenafil -7 Tadalafil3 0 Mean Change in Symptom Score 0 -2 Weeks 6 -2 -3 -4 -5 Vardenafil Placebo -6 -7 12 Placebo Tadalafil 5 mg Tadalafil 20 mg -4 -6 -8 -10 *Not indicated for the treatment of BPH-LUTS. PDE5: phosphodiesterase 5. 1. McVary et al. J Urol. 2007;177:1071-7; 2. Stief et al. Eur Urol. 2008;53:1236-44.; 3. McVary et al. J Urol. 2007;177:1401-7. BPH-LUTS HOME
  39. 39. 39 PDE5 INHIBITORS FOR BPH-LUTS Study Description Length Effect on LUTS McVary et al, 2007 • 369 men with LUTS and ED • Daily sildenafil* vs. placebo 12 weeks • Significant ↓ IPSS • Significant ↑ QoL • ↔ Qmax and Qav Tuncel et al, 2010 • 60 men with BPH-LUTS • Sildenafil* (4 days/week) or tamsulosin or combination 8 weeks • Improved urinary symptoms with tamsulosin/combination • ↑ erectile function with sildenafil/combination McVary et al, 2007 • 281 men with BPH-LUTS • Tadalafil once daily 12 weeks • Significant ↓ IPSS at 6 and 12 weeks • ↔ Qmax and Qav Roehrborn et al, 2008 • 886 men with BPH-LUTS • Daily tadalafil 12 weeks • Significant improvement in urinary symptoms Stief et al, 2008 • 222 men with BPH-LUTS • Vardenafil* twice daily 8 weeks • Significant improvement in irritative/obstructive symptoms and general QoL Gacci et al, 2011 • 60 men with persistent irritative urinary symptoms • Vardenafil* + tamsulosin vs. tamsulosin 12 weeks • Significant reduction of irritative symptoms with combined therapy No change in urinary flow rate with PDE5 inhibitors *Not indicated for the treatment of BPH-LUTS. IPSS: International Prostate Symptom Score; Qav: average flow rate; Qmax: maximum flow rate; QoL: quality of life; PDE5: phosphodiesterase 5. 1. Gacci et al. Eur Urol. 2011;60:809-25. BPH-LUTS HOME
  40. 40. REASONS FOR LACK OF LUTS IMPROVEMENT WITH PDE5I FOR ED Q 40 In the past, why have patients not reported improvements in LUTS when they have used a PDE5 inhibitor for ED? • Treatment of BPH-LUTS with PDE5 inhibitors requires daily dosing • Many patients use PDE5 inhibitors on-demand for ED • Short-acting PDE5 inhibitors (sildenafil/vardenafil) require TID dosing to reach appropriate plasma levels • Only long-acting PDE5 inhibitors are clinically relevant for BPH-LUTS PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor; TID: three-times daily. BPH-LUTS HOME
  41. 41. 41 TADALAFIL 5 MG BUT NOT 2.5 MG IS EFFECTIVE FOR THE TREATMENT OF BPH-LUTS Mean Change in Total IPSS Score from Baseline to Endpoint PLA Run In Week - 4 Baseline Week 0 Placebo Week 4 0 Week 8 Week 12 TAD 2.5 mg TAD 5.0 mg -1 TAD 10.0 mg -2 TAD 20.0 mg -3 Clinically meaningful improvement -4 -5 -6 -7 -8 -9 Tadalafil 2.5 mg p<0.05 at week 4 Tadalafil 5, 10, and 20 mg p<0.01 for weeks 4, 8, and 12 compared to placebo IPSS: International Prostate Symptom Score; PLA: placebo; TAD: tadalafil. 1. Roehrborn et al. J Urol. 2008;180:1228-34. BPH-LUTS HOME
  42. 42. 42 EFFICACY OF PDE5I’S FOR BPH-LUTS LS Mean Change from Baseline in IPSS Total Score 0 Placebo Tadalafil Tamsulosin -1 -2 -3 -4 -5 -6 -7 0 2 4 6 8 10 12 Duration of Treatment (weeks) IPSS: International Prostate Symptom Score; LS: least squares; PDE5I: phosphodiesterase 5 inhibitor. 1. Oelke et al. Eur Urol. 2012;61:917-25. BPH-LUTS HOME
  43. 43. 43 43 TADALAFIL FOR BPH • On June 28, 2012 Health Canada approved tadalafil for the treatment of:1 • The signs and symptoms of benign prostatic hyperplasia (BPH) • Erectile dysfunction (ED) and the signs and symptoms of BPH 1. Cialis Product Monograph. Eli Lilly Canada Inc. BPH-LUTS HOME
  44. 44. 44 44 TAKE HOME MESSAGES • BPH-LUTS and ED often occur together • Pathophysiological link between BPH-LUTS and ED • Suggests a role for the NO/cGMP pathway (which regulates smooth muscle relaxation) • PDE5 inhibitors improve smooth muscle relaxation and are an effective treatment for both ED and BPH-LUTS • Once daily tadalafil is approved in Canada for the treatment of BPHLUTS cGMP: cyclic guanosine monophosphate: NO: nitric oxide; PDE5: phosphodiesterase 5. BPH-LUTS HOME
  45. 45. 45 45 BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS 3 How do I decide which agent to prescribe for BPH-LUTS? BPH-LUTS HOME
  46. 46. 46 46 LEARNING OBJECTIVES • After completing this question participants will be able to: • Evaluate factors that influence treatment decisions for BPH-LUTS • Assess the pharmacological treatment options for BPH-LUTS, including a recently approved PDE5 inhibitor PDE5: phosphodiesterase 5. BPH-LUTS HOME
  47. 47. HOW DO I DECIDE WHICH AGENT TO PRESCRIBE FOR BPH-LUTS? 47 47 • Symptom severity • Bother • Prostate size Other factors: • Side effects • Tolerability BPH-LUTS HOME
  48. 48. 48 48 CUA TREATMENT ALGORITHM LUTS Presentation Mild Symptoms Click on the underlined “criteria” for a specific focus on that algorithm stage Moderate – Severe Symptoms No Significant Bother Small Prostate Large Prostate Watchful Waiting Watchful Waiting or 5-ARI Small Prostate Watchful Waiting Moderate – Severe Bother Large Prostate Small Prostate Large Prostate Watchful Waiting or 5-ARI Alpha-Blocker or Surgical Options Alpha-Blocker or 5-ARI or Combination Therapy or Surgical Options Large prostate is considered to be >30 g (correlates to a PSA of ≥1.5 ng/mL)2,3 5-ARI: 5-alpha reductase inhibitor; PSA: prostate-specific antigen. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Barkin J. Can J Urol. 2011;18 Suppl:14-9; 3. Roehrborn et al. Urology. 1999;53:581-9. BPH-LUTS HOME
  49. 49. 49 49 ALPHA-BLOCKERS • Selective antagonist of α1-adrenoceptors located in: • • • • • Prostate Prostatic capsule Bladder base Bladder neck Prostatic urethra • Help relax smooth muscle in the bladder neck and prostate; allow urine to flow more freely • Selective and non-selective alpha-blockers exist • Non-selective alpha-blockers are not commonly used for BPH-LUTS 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS. BPH-LUTS HOME
  50. 50. 50 50 ALPHA-BLOCKER OPTIONS • First-line options include:1,2 • Selective: • • Alfuzosin • Tamsulosin • Silodosin Non-selective: • Doxazosin • Terazosin • Equal clinical effectiveness for LUTS secondary to BPH • Do not alter the natural progression of the disease • Choice of agent should depend on comorbidities, side effect profile and tolerance 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Rapaflo Product Monograph. Watson Laboratories Inc. BPH-LUTS HOME
  51. 51. 51 51 5-ALPHA REDUCTASE INHIBITORS • Indicated as first-line therapy for men with enlarged prostates: 1,2 • Finasteride  inhibits 5α-reductase Type 2 (prostate) • Dutasteride  inhibits 5α-reductase Type 1 AND 2 (liver, skin and prostate) • Blocks the conversion of testosterone to DHT (responsible for prostate growth) • Treatment with 5-ARIs reduce:1 • • • • Prostate size PSA Long-term risk of acute urinary retention Need for surgery 5-ARIs: 5-alpha reductase inhibitors; DHT: dihydrotestosterone; PSA: prostate-specific antigen. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; 2. Nickel et al. CUAJ. 2010;4:310-6. BPH-LUTS HOME
  52. 52. 52 52 PCPT1 30 25 20 Finasteride Placebo 15 10 5 0 Overall mGs 5-6 mGs 7-10 mGs 8-10 Incidence of Prostate Cancer (%) Incidence of Prostate Cancer (%) 5-ARIs AND PROSTATE CANCER REDUCE2 30 25 20 Dutasteride Placebo 15 10 5 0 Overall mGs 5-6 mGs 7-10 mGs 8-10 • Proposed explanations for the increased incidence of high-grade tumours in 5-ARI arm over placebo:3 • 5-ARIs shrink prostate volume: ↑ likelihood of detecting high-grade disease • 5-ARIs reduce BPH: ↑ sensitivity of PSA and DRE in detecting disease 5-ARIs: 5-alpha reductase inhibitors; DRE: digital rectal exam; mGs: modified Gleason score; PCPT: Prostate Cancer Prevention Trial; PSA: prostate-specific antigen; REDUCE: Reduction by dutasteride of prostate cancer. 1. Thompson et al. NEJM. 2003;349:215-24; 2. Andriole et al. NEJM. 2010;362:1192-202; 3. Hamilton et al. BMC Med. 2011;9:105. BPH-LUTS HOME
  53. 53. 53 53 COMBINATION THERAPY • Combined alpha-blocker and 5-ARI therapy is effective for LUTS associated with prostatic enlargement • Improves symptom score and peak urinary flow greater than either monotherapy option • Delays symptomatic disease progression • Decreased risk of urinary retention and/or prostate surgery 5-ARI: 5-alpha reductase inhibitor. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; 2. Nickel et al. CUAJ. 2010;4:310-6. BPH-LUTS HOME
  54. 54. NEW THERAPEUTIC OPTION: PDE5 INHIBITOR 54 54 • PDE5 inhibitors* promote smooth muscle relaxation to:1 • Improve LUTS • Improve quality of life • Effective in men with or without ED2 GMP Smooth muscle relaxation cGMP Smooth muscle contraction Click here for data on PDE5i’s *Tadalafil is the only PDE5 inhibitor approved for BPH-LUTS (approved in Canada June 2012). cGMP: cyclic guanosine monophosphate; GMP: guanosine monophosphate; PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; BPH-LUTS HOME 2. Broderick et al. Urology. 2010;75:1452-8.
  55. 55. WHEN SHOULD PDE5 INHIBITORS BE CONSIDERED? 55 55 Where would you place PDE5 inhibitors in your BPH-LUTS armamentarium? PDE5: phosphodiesterase 5. BPH-LUTS HOME
  56. 56. PHYTOTHERAPEUTIC AGENTS FOR BPH-LUTS 56 56 • Phytotherapies for BPH-LUTS:1 • Serenoa repens (saw palmetto berry extract) • Pygeum africanum (African plum) Do you recommend phytotherapy to your patients for BPH-LUTS treatment? 1. Nickel et al. CUAJ. 2010;4:310-6. BPH-LUTS HOME
  57. 57. NO SIGNIFICANT IMPROVEMENT OF BPH-LUTS WITH SAW PALMETTO 57 57 CUA guidelines do not recommend phytotherapy for standard care of BPH-LUTS1 • Treatment with saw palmetto resulted in no significant improvement in symptoms or objective measures of BPH2 Click here for data on Saw Palmetto 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Bent et al. NEJM. 2006; 354:557-66. BPH-LUTS HOME
  58. 58. 58 58 BPH-LUTS MEDICATIONS SIDE EFFECTS Q What are the most common side effects with BPH-LUTS medications? Alpha-blockers:1 5α-reductase inhibitors:1 • Retrograde ejaculation • Reduced libido • Erectile dysfunction • Erectile dysfunction Click on drug class • Asthenia • Decreased ejaculate for complete listing • Dizziness volume of side effects • Orthostatic hypotension • Breast tenderness • Nasal congestion PDE5 inhibitors:2 • Headache How do you educate patients • Facial flushing to manage side effects? • Dyspepsia 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS; 2. Cialis Product Monograph. Eli Lilly Canada Inc. BPH-LUTS HOME
  59. 59. 59 59 CASE SCENARIOS Which therapy would you prescribe to a patient with moderate-severe BPH-LUTS? Q Case Description Recommendation Moderate-severe bother (PSA 1.3 ng/mL) α-blocker What if he also had... Diabetes? α-blocker Hypertension? α-blocker ED? α-blocker or PDE5i Signs of prostatic enlargement (PSA >1.5 ng/mL)? 5-ARI Signs of prostatic enlargement (PSA >1.5 ng/mL) and ED? 5-ARI and/or PDE5i Bothersome sexual side effects with α-blocker or 5-ARI? PDE5i 5-ARI: 5-alpha reductase inhibitor; PDE5i: phosphodiesterase 5 inhibitor; PSA: prostate-specific antigen. BPH-LUTS HOME
  60. 60. TAKE HOME MESSAGES: TREATMENT OPTIONS FOR PATIENTS WITH LUTS 60 60 • Alpha-blockers are a first-line option for men with symptomatic bother who desire treatment • 5ARI’s are an effective option for symptomatic patients with demonstrable prostatic enlargement • Combination alpha-blocker and 5-ARI therapy improves symptom score and peak urinary flow vs. monotherapy; appropriate for patients with LUTS associated with prostatic enlargement • A PDE5 inhibitor can be used once-daily in men with moderate to severe symptoms and bother, to effectively reduce symptoms of BPH-LUTS while maintaining sexual function • Phytotherapy is not recommended by the CUA 5-ARI: 5-alpha reductase inhibitor; PDE5: phosphodiesterase 5. BPH-LUTS HOME
  61. 61. 61 61 BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS 4 When should I refer a patient to a urologist? BPH-LUTS HOME
  62. 62. 62 62 LEARNING OBJECTIVES • After completing this question participants will be able to: • Recognize when referral to a specialist is appropriate for an efficient sharedcare approach • Assess indications for surgery and be aware of surgical options for patients with BPH-LUTS BPH-LUTS HOME
  63. 63. WHEN SHOULD I REFER A PATIENT TO A UROLOGIST? 63 63 Considerations: • To rule out prostate cancer (abnormal PSA level and/or abnormal DRE) • Hematuria • Unresponsive to therapy • Patient preference • Surgical management DRE: direct rectal exam; PSA: prostate-specific antigen. 1. Nickel JC. Can Urol Assoc J. 2010;4:127-8. BPH-LUTS HOME
  64. 64. 64 64 WHAT IS CONSIDERED AN ABNORMAL PSA VALUE? • Rapid change in PSA over 1 year1 • 0.75 ng/mL/year when PSA is 4-10 ng/mL • High PSA value for age1,2 • 4.0 ng/mL was originally used to differentiate normal PSA level from pathologic elevation • Age-specific references have been used to improve sensitivity Age Group Parameter3 40-49 50-59 60-69 70-79 Serum PSA Concentration (ng/mL) 0-2.5 0-3.5 0-4.5 0-6.5 PSA: prostate-specific antigen. 1. Izawa et al. 2011. Can Urol Assoc J. 2011;5:235-40; 2. Oesterling et al. JAMA. 1993;270:860-4; 3. Moul et al. J Urol 2007;177:499-503. BPH-LUTS HOME
  65. 65. 65 65 BPH-LUTS ON THE RISE • Approximately 40% of Canadian men >50 years of age are thought to have moderate-severe LUTS1 • Require an approach involving both the primary care practitioner and a urologist for efficient management1,2 • Urologist confirms the diagnosis, rules out prostate cancer, initiates therapy (either watchful waiting, medical or surgical); transfers patient back to primary care practitioner • Primary care practitioner follows LUTS; monitors for progression or complications, monitor PSA (and DRE) if indicated; refer back to urologist, as necessary DRE: direct rectal exam; PSA: prostate-specific antigen. 1. Rawson NS and Saad F. Can Urol Assoc J. 2010;4:123-7; 2. Nickel. Can Urol Assoc J. 2010;4:127-8. BPH-LUTS HOME
  66. 66. 66 66 PROSTATE OBSTRUCTION BPH-LUTS HOME
  67. 67. 67 67 PATIENT SELECTION Q • • • • • When is surgery indicated for BPH-LUTS? Renal insufficiency LUTS complications Patient requests surgical treatment Medication is ineffective Medication side effects are intolerable 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Novara et al. European Urology Supplements. 2006;5:418-29. BPH-LUTS HOME
  68. 68. 68 68 SURGICAL OPTIONS Q What are the surgical options for BPH-LUTS? Prostate Size Very Large (Volume ≥ 80-100 g)1 Open prostatectomy Laser prostatectomy • Holmium • Green light Large (Volume 30-80 g)1 TURP Laser prostatectomy • Holmium • Green light Smaller (Volume <30 g)1 TURP Minimally Invasive • TUMT* • TUNA* *Not insured in Canada. TUMT: transurethral microwave therapy; TUNA: transurethral needle ablation; TURP: transurethral resection of the prostate. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS. Click on the underlined “procedures” for more specific information BPH-LUTS HOME
  69. 69. 69 69 RISKS OF SURGERY • Excessive bleeding requiring blood transfusion • TUR syndrome • Permanent sexual side effects: • Retrograde ejaculation • Erectile dysfunction (less common) • Urinary tract infections • Urinary incontinence • Need for retreatment: • Prostate regrowth • Bladder/urethral strictures TUR: transurethral resection. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS. BPH-LUTS HOME
  70. 70. 70 70 TAKE HOME MESSAGES: REFERRAL AND SURGERY • Consider referral to a specialist: • • • • • To rule out prostate cancer (abnormal PSA/DRE) If presence of hematuria If patient is unresponsive to therapy For surgical management If patient indicates a preference for referral • Surgery should be considered in patients with LUTS complications or where medication is ineffective/intolerable • Patients can be managed in a shared-care approach • Majority of patients with BPH-LUTS will never require a urologist DRE: direct rectal exam; PSA: prostate-specific antigen. 1. Nickel JC. Can Urol Assoc J. 2010;4:127-8. BPH-LUTS HOME
  71. 71. 71 71 BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS 5 How should I follow-up with a BPH-LUTS patient? BPH-LUTS HOME
  72. 72. 72 72 LEARNING OBJECTIVES • After completing this question participants will be able to: • Assess time-to-symptom improvement for each pharmacological option and establish a follow-up strategy • Evaluate options for non-responders BPH-LUTS HOME
  73. 73. HOW SHOULD I FOLLOW-UP WITH A BPH-LUTS PATIENT? 73 73 • Symptom assessment 4-12 weeks following diagnosis • Subsequent follow-up should occur at 6 months and then annually 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS. BPH-LUTS HOME
  74. 74. 74 74 ASSESS TREATMENT RESPONSE • The time required to observe improvement of symptoms varies depending upon the class of medication Drug Class Time for Symptom Improvement α-blockers • • 2-4 weeks to develop fully Hours to days for statistically significant difference over placebo*1,2 5α-reductase inhibitors • At least 6 months1,3 • 4 weeks to reach statistically significant symptom improvement4 PDE5 inhibitors *Silodosin shows statistically significant symptom improvement after 3-4 days. PDE5: phosphodiesterase 5. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS; 2. Rapaflo Product Monograph. Watson Laboratory Inc; 3. Proscar Product Monograph. Merck Canada Inc; 4. Porst et al. Eur Urol. 2011;60:1105-13. BPH-LUTS HOME
  75. 75. 75 75 NON-RESPONSE TO TREATMENT Q What should be done if symptoms have not improved? Consider: • Optimizing current treatment regimen: • Increase dose • Switch agent • Add agent • Re-evaluate diagnosis (consider OAB) • Refer to urologist OAB: overactive bladder. BPH-LUTS HOME
  76. 76. 76 76 TAKE HOME MESSAGES • Follow-up 4-12 weeks following diagnosis • Follow-up should include symptom assessment • Optimize treatment regimen or re-evaluate diagnosis if symptoms have not improved: • • • Increase dose Switch agent Add agent 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS. BPH-LUTS HOME
  77. 77. 77 77 BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS Supplementary Slides BPH-LUTS HOME
  78. 78. 78 78 SYMPTOM SEVERITY MEASURE • International Prostate Symptom Score (IPSS) • Assessed based on reported frequency of 7 symptoms and impact on quality of life • Patients rate questions on a scale of 0-5 • 0 = not at all • 5 = almost always • Sum of answers determines the severity of symptoms Mild: 1-7 Moderate: 8-19 Severe: 20-35 Next 1. Barry et al. J Urol. 1992;148:1549-57. BPH-LUTS HOME
  79. 79. 79 79 IPSS ASSESSMENT Symptom Question 1. Incomplete emptying: How often have you had the sensation of not emptying your bladder? 2. Frequency: How often have you had to urinate less than every 2 hours? 3. Intermittency: How often have you found you stopped and started again several times when you urinate? 4. Urgency: How often have you found it difficult to postpone urination? 5. Weak stream: How often have you had a weak urinary stream? 6. Straining: How often have you had to strain to start urinating? 7. Nocturia: How many times did you typically get up at night to urinate? 8. Quality of life:* If you were to spend the rest of your life with your urinary condition as is, how would you feel about it? Return to Slide 18 *Rated on a scale of 0-6, with 0 being delighted and 6 being terrible. IPSS: International Prostate Symptom Score. 1. Barry et al. J Urol. 1992;148:1549-57. BPH-LUTS HOME
  80. 80. 80 80 SEXUAL HEALTH INVENTORY FOR MEN • Used to assess the severity of ED in sexually active men • Shortened validated version of the IIEF Over the Past 6 months: 1. How do you rate your confidence that you could get and keep an erection? 2. When you had erections with sexual stimulation, how often were your erections hard enough for penetration? 3. During sexual intercourse, how often were you able to maintain your erection after you had penetrated (entered) your partner? 4. During sexual intercourse, how difficult was it to maintain your erection to completion of intercourse? 5. When you attempted sexual intercourse, how often was it satisfactory to you? Return to Slide 23 IIEF: International Index of Erectile Function. 1. Rosen et al. Int J Imp Res. 1999;11:319-26. BPH-LUTS HOME
  81. 81. 81 81 MILD SYMPTOMS LUTS Presentation Mild Symptoms Small Prostate Large Prostate Watchful Waiting Watchful Waiting or 5-ARI Return to Slide 48 5-ARI: 5-alpha reductase inhibitor. 1. Nickel et al. CUAJ. 2010;4:310-6. BPH-LUTS HOME
  82. 82. MODERATE-SEVERE SYMPTOMS: NO BOTHER 82 82 LUTS Presentation Moderate – Severe Symptoms No Significant Bother Small Prostate Watchful Waiting Large Prostate Watchful Waiting or 5-ARI Return to Slide 48 5-ARI: 5-alpha reductase inhibitor. 1. Nickel et al. CUAJ. 2010;4:310-6. BPH-LUTS HOME
  83. 83. MODERATE-SEVERE SYMPTOMS: MODERATE-SEVERE BOTHER 83 83 LUTS Presentation Moderate – Severe Symptoms Moderate – Severe Bother Small Prostate Large Prostate Alpha-Blocker or Surgical Options Alpha-Blocker or 5-ARI or Combination Therapy or Surgical Options Return to Slide 48 5-ARI: 5-alpha reductase inhibitor. 1. Nickel et al. CUAJ. 2010;4:310-6. BPH-LUTS HOME
  84. 84. 84 84 ALL PDE5 INHIBITORS HAVE BEEN SHOWN TO IMPROVE BPH-LUTS Sildenafil1* 0 Vardenafil2* Weeks 6 12 0 -1 8 0 -1 Mean Change in Symptom Score Mean Change in Symptom Score 0 Weeks 4 -2 -3 -4 -5 -6 Placebo Sildenafil -7 Tadalafil3 0 Mean Change in Symptom Score 0 -2 Weeks 6 -2 -3 -4 -5 Vardenafil Placebo -6 -7 12 Placebo Tadalafil 5 mg Tadalafil 20 mg -4 -6 -8 Next -10 *Not indicated for the treatment of BPH-LUTS. PDE5: phosphodiesterase 5. 1. McVary et al. J Urol. 2007;177:1071-7; 2. Stief et al. Eur Urol. 2008;53:1236-44.; 3. McVary et al. J Urol. 2007;177:1401-7. BPH-LUTS HOME
  85. 85. 85 PDE5 INHIBITORS FOR BPH-LUTS Study Description Length Effect on LUTS McVary et al, 2007 • 369 men with LUTS and ED • Daily sildenafil* vs. placebo 12 weeks • Significant ↓ IPSS • Significant ↑ QoL • ↔ Qmax and Qav Tuncel et al, 2010 • 60 men with BPH-LUTS • Sildenafil* (4 days/week) or tamsulosin or combination 8 weeks • Improved urinary symptoms with tamsulosin/combination • ↑ erectile function with sildenafil/combination McVary et al, 2007 • 281 men with BPH-LUTS • Tadalafil once daily 12 weeks • Significant ↓ IPSS at 6 and 12 weeks • ↔ Qmax and Qav Roehrborn et al, 2008 • 886 men with BPH-LUTS • Daily tadalafil 12 weeks • Significant improvement in urinary symptoms Stief et al, 2008 • 222 men with BPH-LUTS • Vardenafil* twice daily 8 weeks • Significant improvement in irritative/obstructive symptoms and general QoL Gacci et al, 2011 • 60 men with persistent irritative urinary symptoms • Vardenafil* + tamsulosin vs. tamsulosin 12 weeks • Significant reduction of irritative symptoms with combined therapy No change in urinary flow rate with PDE5 inhibitors Next *Not indicated for the treatment of BPH-LUTS. IPSS: International Prostate Symptom Score; Qav: average flow rate; Qmax: maximum flow rate; QoL: quality of life; PDE5: phosphodiesterase 5. 1. Gacci et al. Eur Urol. 2011;60:809-25. BPH-LUTS HOME
  86. 86. REASONS FOR LACK OF LUTS IMPROVEMENT WITH PDE5I FOR ED 86 In the past, why have patients not reported improvements in LUTS when they have used a PDE5 inhibitor for ED? Q • Treatment of BPH-LUTS with PDE5 inhibitors requires daily dosing • Many patients use PDE5 inhibitors on-demand for ED • Short-acting PDE5 inhibitors (sildenafil/vardenafil) require TID dosing to reach appropriate plasma levels • Only long-acting PDE5 inhibitors are clinically relevant for BPH-LUTS Next PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor; TID: three-times daily. BPH-LUTS HOME
  87. 87. 87 TADALAFIL 5 MG BUT NOT 2.5 MG IS EFFECTIVE FOR THE TREATMENT OF BPH-LUTS Mean Change in Total IPSS Score from Baseline to Endpoint PLA Run In Week - 4 Baseline Week 0 Placebo Week 4 Week 8 Week 12 0 TAD 2.5 mg TAD 5.0 mg -1 TAD 10.0 mg -2 TAD 20.0 mg -3 Clinically meaningful improvement -4 -5 -6 -7 -8 -9 Tadalafil 2.5 mg p<0.05 at week 4 Tadalafil 5, 10, and 20 mg p<0.01 for weeks 4, 8, and 12 compared to placebo Next IPSS: International Prostate Symptom Score; PLA: placebo; TAD: tadalafil. 1. Roehrborn et al. J Urol. 2008;180:1228-34. BPH-LUTS HOME
  88. 88. 88 EFFICACY OF PDE5I’S FOR BPH-LUTS LS Mean Change from Baseline in IPSS Total Score 0 Placebo Tadalafil Tamsulosin -1 -2 -3 -4 -5 -6 -7 0 2 4 6 8 Duration of Treatment (weeks) 10 12 Return to Slide 52 IPSS: International Prostate Symptom Score; LS: least squares; PDE5I: phosphodiesterase 5 inhibitor. 1. Oelke et al. Eur Urol. 2012;61:917-25. BPH-LUTS HOME
  89. 89. 89 89 SAW PALMETTO DOES NOT IMPROVE BPH-LUTS Changes in Primary and Secondary Outcome Measures Measure Saw Palmetto (n=112) Placebo (n=113) Difference between Groups (95% CI) mean (±SE) change Primary outcomes AUASI score -0.68±0.35 -0.72±0.35 0.04 (-0.93 to 1.01) Peak urinary flow rate (ml/sec) 0.42±0.34 -0.01±0.34 0.43 (-0.52 to 1.38) • No significant differences were observed in symptom improvement between saw palmetto and placebo Return to Slide 55 AUASI: American Urological Association Symptom Index; CI: confidence interval. 1. Bent et al. NEJM. 2006;354:557-66. BPH-LUTS HOME
  90. 90. 90 90 ALPHA-BLOCKER SIDE EFFECTS α-Blocker Side-effect Profile Alfuzosin1 Dizziness and headache, low incidence of postural symptoms, potential for syncope, priaprism and atrial fibrillation Doxazosin2 Dizziness/light-headedness, hypotension/syncope, drowsiness, fatigue (tiredness), swelling of the feet, shortness of breath, painful erection, ejaculation disorders (e.g. retrograde ejaculation) Tamsulosin3 Dizziness, headache, palpitations, hypotension, rhinitis, diarrhea, nausea and vomiting, constipation, asthenia, itching and hives (urticaria), abnormal/retrograde ejaculation, fainting, priaprism Terazosin4 Dizziness/faintness (as a result of blood pressure drop), back pain, constipation, diarrhea, drowsiness or sleepiness, dry mouth, flatulence, headache, impotence, indigestion, decreased libido, nasal congestion, nausea, urinary frequency, weakness or weight gain Silodosin5 Retrograde ejaculation, dizziness, diarrhea, light-headedness upon standing or sitting up abruptly, headache, nasopharyngitis and nasal congestion Return to 5-ARIs Slide 56 5-ARIs: 5-alpha reductase inhibitors. 1. Xatral Product Monograph. Sanofi-Aventis Canada Inc; 2. Cardura Product Monograph. Pfizer Canada Inc; 3. Flomax Product Monograph. Boehringer Ingelheim (Canada) Ltd; 4. Hytrin Product Monograph. Abbott Laboratories; 5. Rapaflo Product Monograph. Watson Laboratories Inc. BPH-LUTS HOME
  91. 91. 91 91 5-ARI SIDE EFFECTS 5-ARI Side-effect Profile • • • Finasteride1 • • • • Dutasteride2 • • • • • • • Impotence/inability to have an erection that continues after stopping the medication Decreased libido Problems with ejaculation, such as a decrease in the amount of semen released during sex Male infertility and/or poor quality of semen Breast tenderness or swelling Testicular pain Depression Impotence Decreased libido Breast disorders (including breast enlargement and tenderness) Ejaculation disorders Dizziness Hair loss Abnormal hair growth PDE5i’s Return to Slide 56 5-ARI: 5-alpha reductase inhibitor; PDE5i: phosphodiesterase 5 inhibitor. 1. Proscar Product Monograph. Merck Canada Inc; 2. Avodart Product Monograph. GlaxoSmithKline Inc. BPH-LUTS HOME
  92. 92. 92 92 PDE5 INHIBITOR SIDE EFFECTS PDE5i Side-effect Profile Sildenafil1 • • • • • Headache Facial flushing Dyspepsia Nasal congestion Abnormal vision colour tinge Tadalafil2 • • • • • Headache Dyspepsia Back pain Myalgia Nasal congestion Vardenafil3 • • • • • Headache Flushing Rhinitis Dyspepsia Sinusitis Return to Slide 56 PDE5i: phosphodiesterase 5 inhibitor. 1. Viagra Product Monograph. Pfizer Canada Inc; 2. Cialis Product Monograph. Eli Lilly Canada Inc; 3. Staxyn Product Monograph. Bayer Inc. BPH-LUTS HOME
  93. 93. 93 93 TRANSURETHRAL RESECTION OF THE PROSTATE Uses electric current to remove tissue from the transition zone of the prostate • Electric current can be monopolar or bipolar • Similar safety and efficacy profiles1 • Bipolar TURP thought to be advantageous2 • Use of isotonic irrigating fluid eliminates need for grounding pads and risk of TUR syndrome Next TUR: transurethral resection; TURP: transurethral resection of the prostate. 1. Méndez-Probst et al. CUAJ. 2011;5:385-9; 2. Hueber et al. Can Urol Assoc J. 2011;5:390-1. BPH-LUTS HOME
  94. 94. 94 94 DISADVANTAGES OF TURP Disadvantages:1,2,3 • Risk of blood transfusion • TUR syndrome • Need for retreatment (14.7% in 8 year follow-up) • Retrograde ejaculation • Risk of impotency • Contraindicated in patients on anticoagulants Return to Slide 66 TUR: transurethral resection. TURP: transurethral resection of the prostate. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS; 3. Yang et al. J Urol. 2001;165:1526-32. BPH-LUTS HOME
  95. 95. 95 95 LASER PROSTATECTOMY Uses laser energy to remove obstructing tissue from the prostate through tissue coagulation or vaporization/ablation1 1. Holmium laser:1 • • • Operational wavelength 2140 nm in pulsed mode Performed at 60-80 W HoLRP on glands <60 g, HoLEP on glands >60 g 2. Green light laser (PVP):2 • • Wavelength of 532 nm Available in 80-W, 120-W and 180-W models3 Return to Slide 66 HoLRP: holmium laser resection; HoLEP: holmium laser enucleation; PVP: photoselective vaporization prostatectomy. 1. Tooher et al. J Urol. 2004;171:1773-81; 2. Hai. Urology. 2009;73:807-10. BPH-LUTS HOME
  96. 96. 96 96 HOLMIUM LASER • 10 year follow-up study has found HoLEP to be equivalent to TURP • Reduced requirement for re-operation1 • May safely be considered a new, size independent, gold standard for symptomatic BPH1 • In prostates >100 g, HoLEP was as effective as open prostatectomy in reducing micturition and the need for re-operation2 • Suitable for patients on anticoagulants3 Disadvantages:4 • Retrograde ejaculation (75-80%) • Dysuria is common • Longer operation time than TURP HoLEP: holmium laser enucleation; TURP: transurethral resection of the prostate. 1. Elmansy et al. J Urol. 2011;186:1972-6; 2. Kuntz et al. Eur Urol. 2008;53:160-6; 3. Elzayat et al. J Urol. 2006;175:1428-32; 4. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS. Return to Slide 66 BPH-LUTS HOME
  97. 97. 97 97 GREEN LIGHT LASER • Ideal for large prostates (30-80 g) • Improvement in symptoms and re-operation rate comparable to TURP1 • Safe and effective in patients on anticoagulants2 Disadvantages:3 • Limited long-term data, particularly with 120-W and 180-W • Longer operation time than TURP • Dysuria is common TURP: transurethral resection of the prostate. 1. Ruszat et al. Eur Urol. 2008;54:893-901; 2. Ruszat et al. Eur Urol. 2007;1031-41; 3. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS. Return to Slide 66 BPH-LUTS HOME
  98. 98. 98 98 OPEN PROSTATECTOMY Obstructive prostatic adenomas are surgically removed through incisions from the inside of the bladder or through the anterior prostatic capsule1 • Oldest surgical treatment for BPH • Considered when prostate is too large (80-100 g) for TURP for fear of:2 • Incomplete resection • Significant bleeding • Risk of TUR syndrome (dilutional hyponatremia) Next TUR: transurethral resection; TURP: transurethral resection of the prostate. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS; 2. Nickel et al. CUAJ. 2010;4:310-6. BPH-LUTS HOME
  99. 99. DISADVANTAGES OF OPEN PROSTATECTOMY • • • • • 99 99 Most invasive of the surgical procedures Risk of bladder stone development Risk of bladder diverticula Risk of incontinence Risk of bladder neck contracture and urethral stricture Return to Slide 66 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS. BPH-LUTS HOME
  100. 100. TRANSURETHRAL INCISION OF THE PROSTATE 10 100 0 Incisions are made in the bladder outlet to improve symptoms • No tissue is removed1 • Ideal for prostate volumes <30 g Advantages over TURP1 Disadvantages1 • • • • • • • • • Reduced bleeding incidents Shorter operation time Avoidance of TUR syndrome Minimal and shorter post-operative bladder irrigation Low risk of retrograde ejaculation Shorter times for catheterization Shorter hospitalization Higher rate of symptom recurrence Need for additional surgery Return to Slide 66 TUR: transurethral resection; TURP: transurethral resection of the prostate. 1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS. BPH-LUTS HOME
  101. 101. 10 101 1 MINIMALLY INVASIVE: TUMT Transurethral microwave therapy (TUMT)1 Microwave heating destroys excess prostate tissue2 • Considered in patients with: • Moderate symptoms • Small to moderate sized prostate gland • Desire to avoid more invasive therapy • Associated with a higher 5 year re-treatment rate than TURP Return to Slide 66 TURP: transurethral resection of the prostate. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Illing. Eur Urol Suppl. 2007;6:701-9. BPH-LUTS HOME
  102. 102. 10 102 2 MINIMALLY INVASIVE: TUNA Transurethral needle ablation (TUNA)1 Generates necrosis by heat application using two needles2 • Considered for younger, active individuals where sexual function is an important quality of life issue • Limited data on long term outcomes • Higher re-treatment rate than TURP2 Return to Slide 66 TURP: transurethral resection of the prostate. 1. Nickel et al. CUAJ. 2010;4:310-6; 2. Illing. Eur Urol Suppl. 2007;6:701-9. BPH-LUTS HOME

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