1. Paolo Coll, M.D Benign Prostatic Hyperplasia.

2. Objectives 1) To describe briefly the prostate functional anatomy. 2) To discuss the diagnostic approach in with Lower Urinary Tract Symptoms “LUTS”. 3) To review Clinical Base Evidence Data for BPH treatment decision. 4) To review principles on pharmacological and non- pharmacological treatment modalities for BPH.

3. Prostate Located between the base of the urinary bladder and the pelvic diaphragm. Surrounded by a fibrous capsule. Located between the base of the urinary bladder and the pelvic diaphragm. Surrounded by a fibrous capsule. Muscular and glandular organ about 3cm both in length and diameter, weight is about 10-20gm. Muscular and glandular organ about 3cm both in length and diameter, weight is about 10-20gm. Two surfaces and five lobes, an apex and a base. Two surfaces and five lobes, an apex and a base. Anterior and posterior surfaces Anterior and posterior surfaces Right and Left Lateral lobes Right and Left Lateral lobes Right and Left Posterior lobes Right and Left Posterior lobes Median Lobe. Median Lobe. Blood and nerve supply branches of inferior vesical and middle rectal arteries + inferior hypogastric plexus. Blood and nerve supply branches of inferior vesical and middle rectal arteries + inferior hypogastric plexus.

4. Prostate Q: Area of prostate affected: inner/outer? A: Area mostly affected in BPH is the inner or internal zone (Paraurethral glands)

5. Prostate Are specific lobes predisposed to prostatic pathologies? Are specific lobes predisposed to prostatic pathologies? YES, 1-Benign Prostatic Hyperplasia 2-Malignant Transformation

6. Introduction and Brief Epidemiology. Benign prostatic hyperplasia (BPH) is a common problem among older men, and is responsible for considerable disability; however, it is an infrequent cause of death. Is defined as a diseased process characterized by stromal and epithelial cell hyperplasia beginning in the periurethral zone of the prostate. Mortality rates for most developed countries in the 1980s were 0.5 to 1.5/100,000

7. BPH Prevalence — The prevalence of histologically diagnosed prostatic hyperplasia increases from 8 percent in men aged 31 to 40, to 40 to 50 percent in men aged 51 to 60, to over 80 percent in men older than age 80 Prevalence — The prevalence of histologically diagnosed prostatic hyperplasia increases from 8 percent in men aged 31 to 40, to 40 to 50 percent in men aged 51 to 60, to over 80 percent in men older than age 80

8. Natural History The natural history of BPH is becoming better understood. The natural history of BPH is becoming better understood. While prostatic mass increases with age, an individual man's symptoms may not. While prostatic mass increases with age, an individual man's symptoms may not. Of men with moderate symptoms followed for five years, about 40% improve, 45% remain unchanged, and only 15% deteriorate.* Of men with moderate symptoms followed for five years, about 40% improve, 45% remain unchanged, and only 15% deteriorate.* *Oesterling J. E. Benign Prostatic Hyperplasia: Medical and Minimally Invasive Treatment Options. N Engl J Med. 1995; 332: 99-109.

9. Natural History II BPH Complications BPH Complications Acute and Recurrent Urinary Retention Recurrent Infections Renal Insufficiency Bladder Descompensation Bladder Stones

10. Bladder Decompensation

11. Q: How often do you monitor patients with BPH for probable malignancy development, though the incidence is low? Q: How often do you monitor patients with BPH for probable malignancy development, though the incidence is low? A: BPH is not a known predisposition or risk factor for prostate malignancy. Consequently no guidelines exist on monitoring BPH symptomatic patients for malignancy.

12. “Doc I can hardly pee” A 75 y/o M comes to your office with a 6 month hx of nocturia, hesitancy, a slow flow of urine, and terminal dribbling. The symptoms have been progressing. Otherwise, he is well and has had no significant medical illnesses. A 75 y/o M comes to your office with a 6 month hx of nocturia, hesitancy, a slow flow of urine, and terminal dribbling. The symptoms have been progressing. Otherwise, he is well and has had no significant medical illnesses. PE: Abdomen: normal. PE: Abdomen: normal. Rectal exam: enlarged prostate, smooth in contour and firm and has no nodules or irregularities. Rectal exam: enlarged prostate, smooth in contour and firm and has no nodules or irregularities.

13. Initial evaluation Initial evaluation 2003 AHCPR* Updated recommendations from previous 1994 guidelines. 2003 AHCPR* Updated recommendations from previous 1994 guidelines. Lower urinary tract pathologies in aging man produce similar, if not identical symptoms. Lower urinary tract pathologies in aging man produce similar, if not identical symptoms. The challenge in patients with LUTS is to establish that the symptoms are BPH related. The challenge in patients with LUTS is to establish that the symptoms are BPH related. US Agency for Health Care Policy and Research (AHCPR)*

14. By following the Clinical Practice Guidelines to exclude other diseases and by using the AUA symptom score to evaluate severity it is possible to determine which men need immediate evaluation by a urologist and which are candidates for watchful waiting or medical therapy. By following the Clinical Practice Guidelines to exclude other diseases and by using the AUA symptom score to evaluate severity it is possible to determine which men need immediate evaluation by a urologist and which are candidates for watchful waiting or medical therapy.

15. Evaluation

16. History A medical history should be taken to identify other causes of voiding dysfunction and comorbidities that may complicate treatment. A medical history should be taken to identify other causes of voiding dysfunction and comorbidities that may complicate treatment. Age. Sx’s frequency and volume. (Symptoms Index score) Previous surgical hx. (Hx of urethritis or urethral injury) Family Hx of BPH or prostate carcinoma. Pharmacological hx. Treatment with drugs that can impair bladder function (anticholinergic drugs) or increase outflow resistance (sympathomimetic drugs) Excessive urine production.

17. The chief complaint of the patient with BPH is usually bothersome “LUTS” typified by: I rritative OR Obstructive Urinary frequency. Urinary frequency. Urgency. Urgency. Urge incontinence. Urge incontinence. Nocturia. Nocturia. Hesitancy Hesitancy Decreased intermittent force of stream. Decreased intermittent force of stream. Sensation of incomplete bladder. Sensation of incomplete bladder. Slow termination/dribbling Slow termination/dribbling

18. Physical Exam A physical exam including both a DRE and a focused neurological examination, should be performed. A physical exam including both a DRE and a focused neurological examination, should be performed. General DRE Focused Neurological Exam* Ambulatory Status LE’S Neuromuscular function Anal sphincter tone

19. Rectal Exam Mr. x, This is not a painful maneuver,you will feel a coldness sensation because of the lubricant and this will be followed by the sensation of having to move your bowels, but this will not happen. Please take a deep breath.. Mr. x, This is not a painful maneuver,you will feel a coldness sensation because of the lubricant and this will be followed by the sensation of having to move your bowels, but this will not happen. Please take a deep breath..

20. Q: Pertinent findings to watch out for on the digital rectal exam? Fast & effective to r/o locally advanced prostatic carcinoma Fast & effective to r/o locally advanced prostatic carcinoma

21. Urinalysis A urinalysis should be performed by dipstick testing or microscopic examination of the sediment to screen for hematuria and evidence of an UTI. A urinalysis should be performed by dipstick testing or microscopic examination of the sediment to screen for hematuria and evidence of an UTI. Bladder Carcinoma Urethral Strictures Urethral-Bladder Stone UTI’S -= <

22. PSA Testing Measurement of PSA should be done in the following individuals: Measurement of PSA should be done in the following individuals: Those with at least a 10yr-life expectancy and to whom knowledge of the presence of prostatic cancer would change management. Those for whom the measurement of their PSA would change the management of their voiding symptoms. *Serum PSA is one predictor of the natural Hx of BPH, higher PSA increased risk of future prostate growth and flow rate deterioration. *Optional Test

23. Urine Cytology *Optional Test *Optional Test Maybe considered in men with a predominance of irritative symptoms, specially with Hx of SMOKING to aid in the Dx of Bladder Carcinoma Insitu or Bladder carcinoma. Maybe considered in men with a predominance of irritative symptoms, specially with Hx of SMOKING to aid in the Dx of Bladder Carcinoma Insitu or Bladder carcinoma.

24. Evaluation II

25. The AUA Symptom Index Tool for BPH and the Disease Specific Quality of Life Question The AUA Symptom score index (Identical to the IPSS) should be done in the initial assessment of each patient presenting with BPH. Seven questions that relate to the associate symptoms. 0-7 MILD 8-19 MODERATE 20-35 SEVERE *Although a Validated test, test clarity, retest, reliability, internal consistency is not a replacement for personal discussion with the patient.

26. Evaluation III

27. Optional Dx Tests I Following the initial evaluation of the patient, urinary flow rate-recording and measurement of post-void residual may be appropriate for certain cases. These tests usually are not necessary prior to the institution of watchful waiting or medical therapy. 1- Neurological disorders known to affect bladder function. 2- Prior failure BPH treatment. 3- Those desiring surgical intervention.

28. Post-Void Residual Urine Volume Residual urine volume can be determined by in-out catheterization, radiographic methods, or USG. Residual urine volume can be determined by in-out catheterization, radiographic methods, or USG. 12CC 200-300CC >12 CC200-300350 CC Q: Based on this information what residual volume needs invasive therapy? A: No level of residual level in and of itself, mandate invasive therapy.

29. PVR “5 Facts” 1-As the result of large test-retest variability and lack of appropriately designed outcome studies is not feasible to establish a PVR “cutpoint” for decision making. 1-As the result of large test-retest variability and lack of appropriately designed outcome studies is not feasible to establish a PVR “cutpoint” for decision making. 2-The Panel recommended the use of PVR measurement as optional in men undergoing non-invasive therapy. 3-Some studies have predicted high Residual volumes with high failure rates of watchful waiting. 4-Possible indicator of BPH, a large residual volume is probably associated with increased risk of infection and is a precursor to bladder decompensation. 5-Although long-term controlled data are lacking many patient maintain fairly large Residual volumes without evidence of UTI’S, Renal insufficiency or bothersome LUTS.

30. Maximal Urinary Flow Rate Greater than 15 mL/sec are thought to exclude clinically important bladder outlet obstruction. >15 mL/sec Below 15 mL/sec are compatible with obstruction due to prostatic or urethral disease; however, this finding is not diagnostic since a low flow rate can also result from bladder decompensation. < 15ml/sec *Among men with BPH, those with maximal flow rates less than 10 mL/sec have better outcomes after surgical intervention than those with higher flow rates. <10mL/sec

31. There is evidence to support that certain tests may be valuable in predicting the response to therapy in specific circumstances. There is evidence to support that certain tests may be valuable in predicting the response to therapy in specific circumstances. Optional Dx Tests II (Invasive) Additional tests such as pressure-flow urodynamic studies, urethrocystoscopy and USG are optional in patients choosing invasive therapies, or if prostate size and anatomical configuration are important considerations for a given treatment modality.

32. Patient Choosing Invasive Therapies Pressure Flow-Studies Measurement of the pressure in the bladder during voiding provides the most accurate means for determining bladder outlet obstruction Measurement of the pressure in the bladder during voiding provides the most accurate means for determining bladder outlet obstruction Urethrocystoscopy Urethral risk factors Ej: Strictures Hematuria Micro-or gross, Endoscopic appearance may guide the choice therapy USG Transrectal or Transabdominal Size, shape and anatomical features Ej: Vesical lobes of the prostate are of importance to select patients for Transurethral microwave heat Tx. TUIP v.s TURP and other Tx Modalities

33. General Overview Watchful Waiting Medical Therapies Minimally Invasive Therapies. Surgical Therapies

34. What is the evidence that medical therapy helps BPH? Drugs are useful if they reduce symptoms, avoid surgery, or prevent complications. Drugs are useful if they reduce symptoms, avoid surgery, or prevent complications. *Evidence that drugs provide anything more than symptomatic benefit is severely limited.

35. Initial Management and Discussion of Medical treatment with the patient. Management of Patients with mild or moderate to Severe BPH symptoms without Bother. Management of patients with moderate to severe BPH symptoms with Bother.

37. “Doc sometimes I can’t pee” A 75 y/o M comes to your office with a 6 month hx of nocturia, hesitancy, a slow flow of urine, and terminal dribbling. The symptoms have been progressing. Otherwise, he is well and has had no significant medical illnesses. A 75 y/o M comes to your office with a 6 month hx of nocturia, hesitancy, a slow flow of urine, and terminal dribbling. The symptoms have been progressing. Otherwise, he is well and has had no significant medical illnesses. PE: Abdomen: normal. PE: Abdomen: normal. Rectal exam: enlarged prostate, smooth in contour and firm and has no nodules or irregularities. Rectal exam: enlarged prostate, smooth in contour and firm and has no nodules or irregularities. AUA Sympto m Index 6 AUA Sympto m Index>2 2

38. Mild-Moderate-Severe Symptoms of BPH without Bother. Non- Bothersome Sx’s of BPH Unaffected quality of life Risks of Medical Therapy Risks of medical therapy outweight the benefits of symptoms improvement.

39. Moderate-Severe Symptoms of BPH With Bother. Alpha adrenergic Blocker Therapy Alpha adrenergic Blocker Therapy Alfuzolin (Uroxatral) Tamsulosin * (Flomax) Terazosin (Hytrin) Doxazosin* (Cardura) Clinical BPH is partly Produced by alpha1- adrenergic-mediated contraction of smooth muscle resulting in bladder outlet obstruction. Equal clinical effectiveness. Different safety profiles. 2 Agents efficacy dose dependency.(Terazosin- Doxazosin) THEORY AGENTSPROFILEADVERSE

40. Moderate-Severe Symptoms of BPH With Bother. 5-Alpha Reductase Inhibitor Therapy 5-Alpha Reductase Inhibitor Therapy THEORYAGENTSPROFILE ADVERSE These drugs act by reducing the size of the prostate gland. The type 2 form of 5-alpha- reductase catalyzes the conversion of testosterone to dihydrotestosteron e in prostatic and other androgen- sensitive tissues. Finasteride (Proscar) Dutasteride (Avodart) Serum dihydrotestosterone concentrations decreased by about 70 percent. Are not appropriate for patients with LUTS without evidence of Prostatic Enlargement. <Risk of Acute Urinary Retention and BPH related Sx. Is partially effective in relieving LUTS.

41. Moderate-Severe Symptoms of BPH With Bother. Combination therapy Combination therapy Combined finasteride-alpha adrenergic antagonist therapy for 6 to 12 months does not appear to be more effective than single-drug therapy for symptom scores and maximal urinary flow rate. However, longer term therapy has shown a benefit from combined therapy. MTOPS trial -Combination therapy reduced the risk of clinical progression by 66 percent, significantly greater than with either drug alone. -Symptom scores improved with all therapies, but to a greater degree with combined therapy - Combination therapy or finasteride alone (but not doxazosin alone), reduced the risk of acute urinary retention and the need for invasive therapy.

43. HERBAL THERAPIES Saw palmetto (Serenoa Repens) DOSAGE AND STANDARDIZATION — Oral: 160 mg twice daily, standardized to contain at least 80% to 90% fatty acids and sterols per dose. PHARMACOLOGY — Excessive formation of dihydrotestosterone (DHT) is believed to stimulate enlargement of the prostate (hyperplasia).There are three mechanisms by which saw palmetto alters the effects of DHT. SUMMARY — Saw palmetto is used in men to improve symptoms of benign prostatic hyperplasia (BPH). Several studies have reported that the effects of saw palmetto are comparable to symptomatic improvements which result from medications commonly used for this disorder. Despite evidence of safety and some efficacy of these products, questions regarding their standardization remain.

44. INVASIVE TREATMENT In general, men with moderate to severe symptoms due to BPH are candidates for invasive therapies. In general, men with moderate to severe symptoms due to BPH are candidates for invasive therapies. Failure of medical treatment. Failure of medical treatment. Recurrent urinary tract infections. Recurrent urinary tract infections. Recurrent or persistent gross hematuria. Recurrent or persistent gross hematuria. Bladder stones. Bladder stones. Renal insufficiency. Renal insufficiency. Refractory urinary retention. Refractory urinary retention.

45. http://www.nucleusinc.com/medical-animations.php?page_no=1&show_anim=turp.mov

46. Transurethral Resection of the Prostate (TURP). Most commonly employed. Most commonly employed. Reduces symptoms in 88 percent of patients. Reduces symptoms in 88 percent of patients. The most frequent complications: Inability to void, Clot retention, secondary infection and bleeding The most frequent complications: Inability to void, Clot retention, secondary infection and bleeding Long-term complications include Long-term complications include retrograde ejaculation (70 percent of treated patients), impotence (14 percent; range: 3 to 32 percent), partial incontinence (6 percent), and total incontinence (1 percent). retrograde ejaculation (70 percent of treated patients), impotence (14 percent; range: 3 to 32 percent), partial incontinence (6 percent), and total incontinence (1 percent). Approximately 10 percent of patients require retreatment within five years. Approximately 10 percent of patients require retreatment within five years.

47. Transurethral Resection of the Prostate

48. Transurethral incision of the prostate (TUIP) Is an endoscopic procedure using only one or two incisions to reduce constriction of the urethra without removing any of the prostate gland. Is an endoscopic procedure using only one or two incisions to reduce constriction of the urethra without removing any of the prostate gland. It is generally offered as a treatment option for younger patients in whom fertility and antegrade ejaculation are important issues. It is generally offered as a treatment option for younger patients in whom fertility and antegrade ejaculation are important issues.

49. Transurethral Ultrasound-Guided Prostatectomy (TULIP, (VLAP), (CLAP), (ILCP), Transurethral ultrasound-guided prostatectomy (TULIP) using a free fiber. Transurethral ultrasound-guided prostatectomy (TULIP) using a free fiber. Free-fiber visually guided laser ablation of the prostate (VLAP). Free-fiber visually guided laser ablation of the prostate (VLAP). Contact laser ablation of the prostate (CLAP) using visual guidance. Contact laser ablation of the prostate (CLAP) using visual guidance. Interstitial laser coagulation of the prostate (ILCP). Interstitial laser coagulation of the prostate (ILCP).

50. Transurethral Vaporization of the Prostate (TUVP) or Transurethral Electrovaporization of the Prostate (TVP) Is now performed using endoscopic electrosurgical equipment to remove prostatic tissue with limited coagulation. Is now performed using endoscopic electrosurgical equipment to remove prostatic tissue with limited coagulation. The procedure provides urinary symptom reduction similar to that of TURP, with less postoperative irritation, urinary retention, blood loss. The procedure provides urinary symptom reduction similar to that of TURP, with less postoperative irritation, urinary retention, blood loss.

51. Transurethral Microwave Thermotherapy (TUMT) Is a single-session, minimally invasive outpatient treatment in which a microwave antenna is placed in a urethral catheter. Is a single-session, minimally invasive outpatient treatment in which a microwave antenna is placed in a urethral catheter. Microwave energy causes deep, rapid tissue heating, while a cooling system circulates water to protect adjacent tissue. Microwave energy causes deep, rapid tissue heating, while a cooling system circulates water to protect adjacent tissue. No major complications, including incontinence and sexual dysfunction, have been reported in patients treated with TUMT. No major complications, including incontinence and sexual dysfunction, have been reported in patients treated with TUMT.

52. Open Prostatectomy Surgical removal of the inner portion of the prostate using a suprapubic or retropubic approach is the oldest and most effective treatment for relieving the symptoms of BPH and increasing maximum urinary flow. Surgical removal of the inner portion of the prostate using a suprapubic or retropubic approach is the oldest and most effective treatment for relieving the symptoms of BPH and increasing maximum urinary flow. Symptomatic improvement occurs in 98 percent of patients who undergo this procedure, and the retreatment rate is only 2 percent. Symptomatic improvement occurs in 98 percent of patients who undergo this procedure, and the retreatment rate is only 2 percent. However, open prostatectomy is the most invasive treatment for BPH and is associated with the most morbidity. Therefore, this procedure is typically reserved for use in patients with a very large prostate gland or structural problems such as a large median lobe that protrudes into the bladder or a large bladder calculus or urethral diverticulum. However, open prostatectomy is the most invasive treatment for BPH and is associated with the most morbidity. Therefore, this procedure is typically reserved for use in patients with a very large prostate gland or structural problems such as a large median lobe that protrudes into the bladder or a large bladder calculus or urethral diverticulum.

53. Conclusions Alpha-1-antagonists reduce symptoms in some patients. Their effect is detectable within 2 weeks. If the patient experiences no clear benefit by 1 month, the drug should be discontinued. The evidence of a significant benefit to risk ratio for finasteride is less clear. It may be useful for men with large prostates; a therapeutic trial of at least 3 months is required. Saw palmetto extracts cannot be recommended because effective doses of available preparations have not been established and evidence of safety and long term efficacy are insufficient. Before using any drug to treat BPH, develop a clear treatment goal with the patient.. If symptoms are not bothersome and there are no indications for urologic evaluation, try "watchful waiting" first. Patients with "mild" symptoms of BPH should be reassured and do not need any treatment. Many patients with "moderate" to "severe" symptoms will improve spontaneously.

54. Resources www.jr2.ox.ac.uk/bandolier www.jr2.ox.ac.uk/bandolier www.jr2.ox.ac.uk/bandolier www.auanet.org www.auanet.org www.auanet.org www.aafp.org www.aafp.org www.aafp.org www.ti.ubc.ca www.ti.ubc.ca