Thursday School December 11, 2014 Richard Hoffman, MD, MPH

 59 y/o Hispanic male with HTN (amlodipine), HLD (simvastatin), and allergic rhinitis (nasal steroid) presents to clinic c/o increasing urinary hesitancy, dribbling, and nocturia over the past 6 months. Based on these lower urinary tract symptoms, you suspect BPH.

 Urinary tract infection (prostatitis, cystitis)  Prostate cancer  Bladder cancer  Urethral stricture/bladder neck contracture  Bladder calculi  Neurogenic bladder  Parkinson  CVA  Diabetes (also glycosuria)

 AUA symptom index?  Digital rectal examination?  Urinalysis?  Post-void residual urine volume?  Peak urinary flow?  Basic metabolic panel?  PSA?  Renal ultrasound?

 AUA symptom index?  Digital rectal examination?  Urinalysis?  Post-void residual urine volume?  Peak urinary flow?  Basic metabolic panel?  PSA?  Renal ultrasound?

 Benign proliferation of stromal and epithelial tissue  Obstruction ▪ Static (bulk enlargement) ▪ Dynamic (smooth muscle)  Irritation ▪ Bladder instability

 Obstructive symptoms  Incomplete emptying  Weak stream  Intermittency  Straining  Irritative symptoms  Frequency  Urgency  Nocturia

 How often in the past month (all but nocturia)?  Scored from 0 (never) to 5 (almost always)  Nocturia  Scored from 0 (never) to 5 (5 or more times)  Scoring  0 to 7: mild  8 to 19: moderate  20 to 35: severe

 Prostate enlargement  Prostate cancer  Nodule, induration, asymmetry  Rectal sphincter tone

 Bacteria  White blood cells  Glucose  Red blood cells

 Bladder outlet obstruction  Renal disease

 Post-void residual urine volume  Suspected obstruction ▪ Bladder scan  Peak urinary flow rate  Low rates (< 15 ml/s) could be due to obstruction or decompensated bladder

 PSA  Informed decision making  Abnormal DRE, risk factors  Renal ultrasound  Elevated creatinine, UTI

 DRE normal  Urinalysis negative  Creatinine normal  AUA symptom score = 7

 Behavioral (watchful waiting)  Medications  5-ARI  Alpha blockers  Anti-cholinergics  PDE-5 inhibitors

 Preference sensitive; however, behavioral appropriate initial approach for mild to moderate symptoms  Limit fluid intake before bedtime, especially caffeine and alcohol  Double voiding before going to bed  Avoid medications: anticholinergics, antihistamines, alpha agonists, diuretics

 Alpha blockers  5-alpha reductase inhibitors  Anticholinergics  Phosphodiesterase-5 inhibitors  Herbal therapies

 Urinary retention  Renal insufficiency  Recurrent infections  Bladder stones  Hematuria

 Symptoms progressing/bothersome on medical management  Medical management not tolerated

 TURP  Open prostatectomy  TUIP  TEVAP  TUNA  Laser coagulation/prostatectomy  TUMT

 TURP is gold standard treatment  Improves symptom scores by 10 points(70%)  Reduces treatment failure vs. watchful waiting by 52% (8% vs. 17%) ▪ Death, intractable retention, residual urine volume > 350 ml, bladder stone, incontinence, AUA sx score ≥ 24, doubling of creatinine

 TURP  Requires hospitalization, catheter  Complications ▪ Bleeding, infection, stricture, TUR syndrome, retrograde ejaculation

 FDA-approved drugs  Terazosin, Doxazosin, Tamsulosin, Alfuzosin, Silodosin  Titrate terazosin, doxazosin  Indication  Moderate/severe symptoms  Small prostate (< 40 gms)

 Mechanism of action  Relaxes smooth muscle in bladder neck, prostate  Effective within 1-2 weeks  First-line agent  Benefits  Improves symptom scores by 30 to 40%

 Side effects  Hypotension/dizziness ▪ Less with tamsulosin  Asthenia  Floppy iris syndrome (cataract surgery) ▪ Tamsulosin  Nasal congestion  Headache

 A patient returns to clinic. He was taking terazosin 15 mg for BPH, but was just summering in Alaska. His medications did not reach him and he ran out 2 months ago. His lower urinary tract symptoms are quite bothersome.

 Restart terazosin at same dose  Restart terazosin at low dose, titrate  Prescribe tamsulosin

 Restart terazosin at same dose  Restart terazosin at low dose, titrate  Prescribe tamsulosin

 FDA-approved drugs  Finasteride  Dutasteride  Indication  Moderate/severe symptoms  Not tolerating alpha blocker  Large prostate (> 60 gm) ▪ Can combine with alpha blocker

 Mechanism of action  Blocks conversion of testosterone to dihydrotestosterone (prostate, hair follicles)

 Isolated village of Dominican Republic  Children appearing to be girls turned into men at puberty “pseudohermaphrodites” Imperato-McGinley J. Science 1974;186:1213

 Prostate remains small  No prostate cancer  No hairline recession  5-alpha-reductase deficiency

 Benefits  Reduces urinary symptoms by ~20%  Reduces risk of surgery, urinary retention especially when combined with alpha blocker  Side effects  Erectile dysfunction  Decreased libido  Gynecomastia

 Prostate cancer  Reduces PSA by 2-fold  Reduces risk for cancer by 25%  Increase risk for high-grade cancers  FDA would not allow manufacturers to market for cancer prevention and issued warning “be aware that 5-ARIs may increase the risk of high-grade prostate cancer”

 Treat overactive bladder in BPH  Combined with α-blocker > α-blocker  Approved drugs  Tolterodine, oxybutinin  UpToDate®: consider for men with irritative symptoms, without elevated PVR  I would refer to GU

 Treat BPH with ED  Medications  Sildenafil, vardenafil, tadalafil  UpToDate®: consider for men with ED and mild/moderate BPH  Modest evidence, most placebo-controlled, not better than alpha blocker

 Update on AUA guideline on the management of benign prostatic hyperplasia. McVary KT et al. J Urol 2011;185:1793.  The American Urological Association symptom index for benign prostatic hyperplasia. Barry MJ, et al. J Urol 1992;148:1549.  A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. Wasson JH, et al. NEJM 1992; 332:75.  The influence of finasteride on the development of prostate cancer. Thompson IM, et al. NEJM 2003;349:215.  Effect of dutasteride on the risk of prostate cancer. Andriole GL, et al. NEJM 2010; 362:1192.  Finasteride for benign prostatic hyperplasia. Tacklind J. et al. Cochrane Database Syst Rev 2010;Oct 6 (10): CD006015]  Terazosin for benign prostatic hyperplasia. Wilt TJ, et al. Cochrane Database Syst Rev 2002; (4): CD003851

 Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. Barry MJ, et al. JAMA 2011; 306:1344.  Laser prostatectomy for benign prostatic obstruction. Hoffman RM, et al. Cochrane Database Syst Rev 2004; (1):CD  Microwave thermotherapy for benign prostatic hyperplasia. Hoffman RM, Langsjoen J, et al. Cochrane Database Syst Rev 2012; Sep 12;9:CD  A systematic review and meta-analysis on the use of PDE-5 inhibitors alone or in combination with a-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Gacci M, et al. Eur Urol 2012;61:994.  The efficacy and safety of combined therapy with a-blockers and anticholinergics for men with BPH. Filson CP, et al. J Urol 2013;190: