Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms

March 26, 2014 7:45 AM – 9:00 AM Anaheim, California

Sponsored by pmiCME

Educational Partner

Session 1: The Evaluation and Treatment of Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms in the Primary Care Setting Learning Objectives 1.

2. 3.

Describe the pathophysiology and common comorbidities of benign prostatic hyperplasia and lower urinary tract symptoms (BPH/LUTS) Implement comprehensive assessment of patients with BPH/LUTS Select treatment options available to effectively treat BPH/LUTS

Faculty Martin Miner, MD Chief of Primary Care and Community Medicine The Miriam Hospital Co-Director Men’s Health Center Clinical Associate Professor of Family Medicine and Urology Warren Alpert Medical School Brown University Providence, Rhode Island

Dr Martin Miner clinical associate professor of family medicine and urology at Warren Alpert Medical School, Providence, Rhode Island, has practiced preventive and primary care medicine for more than 28 years and is currently chief of family and community medicine at The Miriam Hospital. He is the author of more than 75 publications in the areas of erectile dysfunction and cardiovascular disease, benign prostatic hyperplasia and lower urinary tract symptoms in reference to male sexuality, and hormonal replacement therapy in men. Dr Miner is president elect of the American Society for Men’s Health, associate editor of the Journal of Men’s Health, and serves on multiple journal boards and reviews for several publications. He is currently active in several research studies on men’s health, and was the recipient of the dean’s teaching excellence award in 2003 and 2007.

Matt T. Rosenberg, MD Medical Director Mid-Michigan Health Centers Chief, Department of Family Medicine Foote Health System Jackson, Michigan

Dr Matt Rosenberg earned his medical degree at the University of California, Irvine, where he trained in general surgery. He also trained in urologic surgery at Brigham and Women’s Hospital, Boston before changing fields to general practice. Dr Rosenberg has a special interest in the medical management of urologic diseases and has authored or coauthored articles appearing in Urology, Journal of Urology, BJU International, International Journal of Clinical Practice, and other peer reviewed journals. He now practices in Jackson, Michigan; serving as medical director of Mid-Michigan Health Centers, and on staff at Allegiance Health, where he served as chief of the department of family medicine from 2003 to 2006. Dr Rosenberg is section editor of urology at the International Journal of Clinical Practice and is founder and chairman of the

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Urologic Health Foundation: a nonprofit group dedicated to the education of primary care physicians in the field of genitourinary disease. In 2011, he was appointed by the American Urological Association office of education to be the Coordinator of Primary Care Education.

Faculty Financial Disclosure Statements The presenting faculty reported the following: Dr Miner receives consultant honoraria from AbbVie and research funding from Forest. Dr Rosenberg receives consultant and speaker honoraria from Astellas, Eisai, Ferring, Forest, Horizon, Ortho-McNeil, Lily, and Pfizer.

Education Partner Financial Disclosure Statement The content collaborators at Miller Medical Communications, LLC, report the following: Lyerka D. Miller, PhD, has no financial relationships to disclose.

Suggested Reading List Issa MM, Fenter TC, Black L, Grogg AL, Kruep EJ. An assessment of the diagnosed prevalence of diseases in men 50 years of age or older. Am J Manag Care. 2006;12(4 suppl):S83-S89. Bushman W. Etiology, epidemiology, and natural history of benign prostatic hyperplasia. Urol Clin North Am. 2009;36(4):403-415. Rosen R, Altwein J, Boyle P, et al. Lower urinary tract symptoms and male sexual dysfunction: the multinational survey of the aging male (MSAM-7). Eur Urol. 2003;44(6):637-649. Rosenberg MT, Miner MM, Riley PA, Staskin DR. STEP: simplified treatment of the enlarged prostate. Int J Clin Pract. 2010;64(4):488-496. McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185(5):1793-1803. Lee RK, Chung D, Chughtai B, Te AE, Kaplan SA. Central obesity as measured by waist circumference is predictive of severity of lower urinary tract symptoms. BJU Int. 2012;110(4):540-545. Kupelian V, McVary KT, Kaplan SA, et al. Association of lower urinary tract symptoms and the metabolic syndrome: results from the Boston area community health survey. J Urol. 2013;189(1 Suppl):S107-S114. Elterman DS, Barkin J, Kaplan SA. Optimizing the management of benign prostatic hyperplasia. Ther Adv Urol. 2012;4(2):7783. Rosenberg MT, Staskin D, Riley J, Sant G, Miner M. The evaluation and treatment of prostate-related LUTS in the primary care setting: the next STEP. Curr Urol Rep. 2013;14(6):595-605. Gacci M, Corona G, Salvi M, et al. A systematic review and meta-analysis on the use of phospodiesterase 5 inhibitors alone or in combination with -blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012;61(5):994-1003. Lythgoe C, McVary KT. The use of PDE-5 inhibitors in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. Curr Urol Rep. 2013;14(6):585-594. Kapoor A. Benign prostatic hyperplasia (BPH) management in the primary care setting. Can J Urol. 2012;19 (Suppl 1):10-17.

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Kaplan SA, Wein AJ, Staskin DR, Roehrborn CG, Steers WD. Urinary retention and post-void residual urine in men: separating truth from tradition. J Urol. 2008;180(1):47-54. Casabé A, Roehrborn CG, Da Pozzo LF, et al. Efficacy and safety of the coadministration of tadalafil once daily with finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia. J Urol. 2014;191(3):727-733. McConnell JD, Roehrborn CG, Bautista OM, et al; for the Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349(25):2387-2398. Fourcade RO, Lacoin F, Rouprêt M, et al. Outcomes and general health-related quality of life among patients medically treated in general daily practice for lower urinary tract symptoms due to benign prostatic hyperplasia. World J Urol. 2012;30(3):419-426.

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Presenter Disclosure Information

SESSION 1

The following relationships exist related to this presentation:

7:45–9am

► Dr Rosenberg has served as a consultant or speaker for Astellas, Eisai, Ferring, Forest, Horizon, Lilly, Ortho-McNeil, and Pfizer.

The Evaluation and Treatment of Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms in the Primary Care Setting

► Dr Miner has served as a consultant for AbbVie and has received research funding from Forest.

Off-Label/Investigational Discussion

SPEAKERS

► In accordance with pmiCME policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations.

Matt T. Rosenberg, MD Martin Miner, MD

Drug List Generic Name

Faculty

Fortamet, Glucophage, Glucophage XR, Glumetza

Linagliptin

Tradjenta

Enalapril

Epaned, Vasotec

Atorvastatin

Lipitor

Alfuzosin

Matt T. Rosenberg, MD

Martin Miner, MD

Chief of Primary Care and Community Medicine The Miriam Hospital Co-Director, Men’s Health Center Clinical Associate Professor of Family Medicine and Urology Warren Alpert Medical School Brown University Providence, Rhode Island

Medical Director Mid-Michigan Health Centers Chief Department of Family Medicine Foote Health System Jackson, Michigan

Learning Objectives

Implement comprehensive assessment of patients with BPH/LUTS

•

Select treatment options available to effectively treat BPH/LUTS

Cardura

Silodosin

Rapaflo

Tamsulosin

Flomax

Terazosin

Hytrin

Tadalafil

Adcirca, Cialis Detrol, Detrol LA, Detrusitol

Trospium chloride

Sanctura, Spasmex, Spasmolyt, Trosec

Darifenacin

Enablex

Fesoterodine

Toviaz

Oxybutynin

Ditropan, Gelnique, Lyrinel XL, Oxytrol

Solifenacin

VesiCare

Mirabegron

Myrbetriq

Dutasteride

Avodart

Finasteride

Proscar

Dutasteride/Finasteride

Jalyn

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Myths

After participating in this educational activity the participant should be able to: • Describe the pathophysiology and common comorbidities of BPH/LUTS

•

Uroxatral

Doxazosin

Tolterodine

3

Trade Name

Metformin

• • •

LUTS in the male is a normal part of aging

•

PSA testing has no use in the evaluation of LUTS

LUTS in the male is always related to the prostate The provider needs urodynamic testing to facilitate the diagnosis LUTS

BPH=benign prostatic hyperplasia; LUTS=lower urinary tract symptoms. 5

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1

Realities

• • • •

A Typical Patient?

• LUTS in the male is not a normal part of aging LUTS can come from the bladder, prostate, or medical causes The evaluation of LUTS can be performed in the PCP office with an adequate history, physical, and a few simple labs The PSA is a surrogate marker for prostate size

•

Stephen is a 65-year-old obese, hypertensive male with type 2 DM At the encouragement of his wife, he admits that he has some issues “down there” – He complains of urinary urgency, a poor stream, frequency, and nocturia – He has tolerated these symptoms for several years as he thought it was a natural part of aging

PCP=primary care physician.

DM=diabetes mellitus. 11

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Current Medications

• • • •

Physical Examination • • • •

Metformin 500 mg twice daily Linagliptin 5 mg daily Enalapril 10 mg daily Atorvastatin 10 mg daily

• • • •

Height: 5’ 9” Weight: 217 lb BMI: 32 kg/m2 BP: 140/80 mm Hg

Neck: No thyromegaly Lungs: Clear Cor S1S2S4 Genital: testes descended, no masses, no varicocele, normal size (30-35 g); no prostate nodule palpated

• • • •

Feet: no ulcers Neurologic: mild decreased sensation to 10-g monofilament; no visual field cuts Skin/hair: normal beard, normal male pattern hair in genital axilla No gynecomastia

BP=blood pressure. 13

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Laboratory Results

• • • • • • • • •

CLUES in the Patient Presentation

•

HbA1C: 6.8% at his last check-up 6 months ago Cr: 1.3 mg/dL PSA: 1.7 ng/mL TC: 210 mg/dL LDL-C: 110 mg/dL HDL-C: 35 mg/dL TG: 250 mg/dL Microalbumin: undetectable GFR: 50 mL/min

•

Stephen is a 65-year-old obese, hypertensive male with type 2 DM At the encouragement of his wife, he admits that he has some issues “down there” – He complains of urinary urgency, a poor stream, frequency, and nocturia – He has tolerated these symptoms for several years as he thought it was a natural part of aging

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2

Function of the Prostate

More Clues

• • • • • • • • •

HbA1C: 6.8% at his last check-up 6 months ago Cr: 1.3 mg/dL PSA: 1.7 ng/mL TC: 210 mg/dL LDL-C: 110 mg/dL HDL-C: 35 mg/dL TG: 250 mg/dL Microalbumin: undetectable GFR: 50 mL/min

Normal Function

Abnormal Function

•

•

•

•

Obstruction of urinary flow Poor function seen as failure to void

Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546.

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Benign Prostatic Hyperplasia

•

Produces fluid for seminal emission Does not compress the urethra, thereby allowing unobstructed flow

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Natural History of Prostate Growth •

A common condition as men age – By sixth decade: >50% of men have some degree of hyperplasia

According to data from a study by Roehrborn and colleagues, a 55-year–old man who has a 30-mL prostate volume (PV), is experiencing symptoms, and has a PSA of 1.5 ng/mL can expect his prostate to approximately double in size over the next 15 years.

– By eighth decade: >90% of men will have hyperplasia

•

In only a minority of patients (approximately 10%) will this hyperplasia be symptomatic and severe enough to require medical treatment or surgical intervention

Age

55 yrs

60 yrs

65 yrs

70 yrs

PV

30 mL

>40 mL

>50 mL

>61 mL

PSA McVary KT, et al. J Urol. 2011;185(5):1793-1803..

Increase in bother Decrease in quality of life

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Risk Evaluation of BPH-LUTS Progression

Complications of BPH Progression Worsening of symptoms

1.5 ng/mL

Roehrborn C, et al. J Urol. 2000;163(1):13-20.

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Baseline Factors as Predictors

Five risk factors The Enlarging Prostate

1. Total prostate volume ≥31 mL

Need for surgical intervention

2. PSA ≥1.6 ng/mL 3. Age ≥62

Not usually evaluated by the PCP

Alarm symptoms

4. Qmax 30 mL • Inflammation • Elevated IPSS • Refractory to treatment • Poor flow • Genetics • History of AUR • High waist circumference • Increasing age • PSA >1.5 ng/dL • PVR >50 mL • Increasing bother • Reduced physical activity

%

Hypertension

Roehrborn CG, et al; BPH Registry and Patient Survey Steering Committee. BJU Int. 2007;100(4):813-819.

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LUTS-BPH

Comorbidity with BPH-LUTS (N=6909)

Pelvic atherosclerosis

BPH-LUTS ED

•

Lower Urinary Tract Symptoms (LUTS) can be of urologic origin, which includes the prostate and bladder, or can be medical in nature

•

A comprehensive history, physical, and laboratory evaluation will generally provide the needed clues

Steroid hormone unbalance

Comorbidities Hypertension, Metabolic Syndrome, Diabetes, etc cGMP=cyclic guanosine monophosphate; NO=nitric oxide; ROCK=Rho-associated protein kinase. Gacci M, et al. Eur Urol. 2011;60(4):809-825.

Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546.

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Medications Can Cause or Exacerbate BPH/LUTS

Examples in the Medical or Surgical History That Can Cause or Confound LUTS • •

Poorly controlled diabetes causing polyuria/polydipsia

Medication

Antihypertensive diuretics can cause frequency and urgency whereas some cold medications (eg, α-agonists) commonly cause flow problems

Sedatives

•

Congestive heart failure causing nighttime fluid mobilization

-Agonists

Increased outlet resistance, voiding difficulty

ß-Blockers

Decreased urethral closure, stress incontinence

• •

Recent surgery causing immobilization or constipation

Anticholinergics

Angiotensin-converting enzyme First-generation antihistamines Cholinesterase inhibitors

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Abdominal Neurological

Constipation

– Meatus and testes

•

Urinalysis

•

A random or fasting blood sugar

•

Prostate specific antigen

– Infection, blood, crystals – The urine is not an adequate screener for diabetes because the blood sugar must be above 180 mg/dL before it spills into the urine

– Prostate specific, not cancer specific, but can be used in screening – Excellent as a surrogate marker for prostate size

Rectal – Tone

• PSA is more accurate than a DRE when estimating prostate size • A PSA of 1.5 ng/mL equates to a prostate volume of at least 30 grams (mL)

– Prostate size, shape, nodules and consistency

Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546. Bosch JL, et al. Eur Urol. 2004;46(6):753-759. Roehrborn CG, et al. Urology. 1999;53(3);581-589.

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International Prostate Symptom Score (IPSS) Questionnaire

Optional Tests

• • • •

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– Diabetes

Genitourinary

Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546. Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496.

Increase outlet resistance Precipitate urge incontinence

Laboratory Tests

– Mental and ambulatory status, neuromuscular function

•

Induce cough, stress urinary incontinence

Opioids

– Tenderness, masses, distension

•

Reduce bladder smooth muscle contractility

Newman DK. Nurse Pract. 2009;34(12):33-45. Dubeau CE. J Urol. 2006;175(3 Pt 2):S11-S15. Wyman JF, et al. Int J Clin Pract. 2009;63(8):1177-1191. Gill SS, et al. Arch Intern Med. 2005;165(7):808-813. Lavelle JP, et al. Am J Med. 2006;119(3 suppl 1):37-40.

A Focused Physical Examination

•

Diuresis Impaired contractility, voiding difficulty, overflow incontinence

Calcium-channel blockers

The temporal relationship may offer a clue

•

Confusion, secondary incontinence

Alcohol, caffeine, diuretics

Poor urinary hygiene

Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546. Burgio KL, et al. Int J Clin Pract. 2013;67(6):495-504.

LUTS-Related Effect

International Prostate Symptom Score (IPSS) Voiding Diary Post Void Residual (PVR) Urine Flow Rate (Qmax)

Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546. Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496.

McVary KT, et al. J Urol. 2011;185(5):1793-1803. http://www.urospec.com/uro/Forms/ipss.pdf. Accessed February 12, 2014.

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The Purpose of the Voiding Diary • •

Post Void Residual

Identifies voiding frequency and volumes Differentiates behavioral problems as opposed to ones of pathologic origin

FACTS

• •

– Voiding frequently after drinking the 40-ounce cola at lunch or break (behavioral) – Voiding frequently of small amounts only at work as a result of always being in a rush (behavioral) – Voiding frequently of small amounts (OAB) – Voiding frequently of large amounts (overproduction of fluid – medical cause or excessive intake)

• •

WHEN TO CHECK

• • •

Alerts the patients as to their habits and may offer opportunities for improvement Can help monitor efficacy of treatment

Wyman JF, et al. Int J Clin Pract. 2009;63(8):1177-1191.

Clinical suspicion Refractory to therapy for BPH Prior to pharmacologic treatment of OAB

Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496. AUA Guidelines. http://www.auanet.org/education/guidelines/benign-prostatic-hyperplasia.cfm. Accessed February 12, 2014.

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The Next STEP

LUTS and Indications for Referral • • • • • • • • • • •

50 mL or less represents adequate voiding 200 mL or more is consistent with clinically significant inadequate voiding

Suspicion of neurologic cause of symptoms History of recurrent UTI or other infection Findings or suspicion of urinary retention Abnormal prostate exam (nodules) Microscopic or gross hematuria History of genitourinary trauma Prior genitourinary surgery Uncertain diagnosis Meatal stenosis Elevated PSA Pelvic pain

Rosenberg MT, et al. Int J Clin Pract. 2007;61(9):1535-1546. Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496.

Rosenberg MT, et al. Curr Urol Rep. 2013;14(6):595-605.

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The Next STEP: Step 1

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STEP 1: Informed Surveillance If the patient has symptoms but no bother and no complications

Patients who opt for this option may benefit from:

Rosenberg MT, et al. Curr Urol Rep. 2013;14(6):595-605.

• • •

Lifestyle changes (exercise, weight management)

• •

Medication modification

Limitations of fluids Bladder training focused on timed and complete voiding (behavior modification) Although LUTS secondary to BPH is not often a lifethreatening condition, the impact of LUTS/BPH on quality of life (QoL) can be significant and should not be underestimated

Rosenberg MT, et al. Curr Urol Rep. 2013;14(6):595-605. Burgio KL, et al. Int J Clin Pract. 2013;67(6):495-504.

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The Next STEP: Step 2

Rationale for Alpha-Blocker or PDE5i Therapy

Alpha-blockers PDE5i’s

Dynamic component Rapidly relieve symptoms by inhibiting contraction of prostate smooth muscle PDE5i=phosphodiesterase 5 inhibitor.

Rosenberg MT, et al. Curr Urol Rep. 2013;14(6):595-605.

Rosenberg MT, et al. Int J Clin Pract. 2010;64(4):488-496. Roehrborn CG. Rev Urol. 2009;11(suppl 1):S1-S8. Rosenberg MT, et al. Curr Urol Rep. 2013;14(6):595-605.

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Step 2: Alpha-Blockers (AB)

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Step 2: Alpha-Blockers

Single medication therapy with an AB is appropriate for the symptomatic patient who has identified bother and has a PSA of