Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms: Individualized Management in Primary Care

Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms: Individualized Management in Primary Care

Benign Prostatic Hyperplasia and
Lower Urinary Tract Symptoms:
Individualized Management in
Primary Care
September 19, 2013
Boston Convention & Exhibition Center
Boston, Massachusetts
Education Partner:
Integritas Communications
Session 5: Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms:
Individualized Management in Primary Care
Learning Objectives
1.
2.
3.
4.
5.
Describe pathophysiologic mechanisms in benign prostatic hyperplasia and lower urinary tract symptoms (BPHLUTS) and relationships to comorbid conditions and therapeutic approaches.
Conduct comprehensive assessments of patients with suspected BPH and associated LUTS.
Evaluate the mechanisms of action and clinical profiles of α-blockers, 5-α reductase inhibitors (5-ARIs), and
phosphodiesterase type 5 (PDE-5) inhibitors in the treatment of BPH-LUTS with and without ED.
Combine pharmacologic and nonpharmacologic interventions for BPH-LUTS based on symptom severity, common
comorbidities, risk of disease progression, and patient goals.
Monitor treatment efficacy and adherence in patients with BPH-LUTS to guide therapeutic restructuring and optimize
patient outcomes.
Faculty
Matt T. Rosenberg, MD
Medical Director
Mid-Michigan Health Centers
Chief, Department of Family Medicine
Foote Health System
Jackson, Michigan
Dr Matt T. Rosenberg earned his medical degree at the University of California, Irvine, School of Medicine, where he trained in
general surgery. He also trained in urologic surgery at Brigham and Women’s Hospital in Boston, Massachusetts, 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
published in Urology, Journal of Urology, BJU International, International Journal of Clinical Practice, and other peer-reviewed
journals.
He practices in Jackson, Michigan, 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 for the
International Journal of Clinical Practice and is founder and chairman of the 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’s office of education to be the coordinator of primary care education.
David R. Staskin, MD
Associate Professor of Urology
Tufts University School of Medicine
Director, Center for Male and Female Pelvic Health
Steward-St. Elizabeth’s Medical Center
Boston, Massachusetts
Dr David R. Staskin graduated from Hahnemann Medical College in Philadelphia, Pennsylvania, in 1979. He interned at the
University of California, San Diego, and then served as a fellow at the National Kidney Foundation, University of Pennsylvania,
and the University of California, Los Angeles. He joined the faculty of Boston University Medical Center in 1985, then the faculty
of Harvard University-Beth Israel Medical Center in 1989. From 2002 to 2008, Dr Staskin was a member of the faculty of Weill
Cornell Medical College at New York Presbyterian Hospital. He recently joined the department of urology at Tufts Medical
Center in Boston, Massachusetts, as an associate professor.
Dr Staskin belongs to many leading urological associations and committees, including the Health and Human Services
Incontinence Guidelines (member); the World Health Organization’s International Consultation on Incontinence Guidelines for
Incontinence (chairperson); the American Urological Association committee “Surgical Management of Female Stress Urinary
Session 5
Incontinence”; the Society of Urodynamics and Female Urology (board of directors); the American Urogynecological Society
(former board of directors); and the American Association of Clinical Urologists (board of directors).
He also serves on the following journals as a reviewer: International Urogynecology Journal (editorial board); Current Urology
(editorial board); Journal of Urology; Urology; Neurology and Urodynamics; British Journal of Urology International; and The New
England Journal of Medicine.
Dr Staskin has published extensively in the areas of female urology, neurourology, and urodynamics. He is the co-editor of the
Textbook of Female Urology and Urogynecology (Cardozo and Staskin, eds.), which was awarded the British Medical Society’s first
prize for the best second edition medical textbook of 2006.
Dr Staskin is the inventor of SPARC Sling System (American Medical Systems) and has contributed significantly to the
development of the Monarc and BioArc slings and Apogee and Perigee for pelvic prolapse repair systems.
Steven A. Kaplan, MD—Virtual Presenter
E. Darracott Vaughan Jr. Professor of Urology
Chief, Institute for Bladder and Prostate Health
Weill Cornell Medical College
Director, Iris Cantor Men’s Health Center
New York Presbyterian Hospital
Weill Cornell Medical Center
New York, New York
Dr Steven A. Kaplan received a BS in biochemistry from The City University of New York—Brooklyn College in 1978, graduated
from Mount Sinai School of Medicine in 1982, and was elected to the Alpha Omega Alpha Medical Honor Society. Dr Kaplan’s
postgraduate training included an internship and residency in the department of surgery at Mount Sinai Hospital as well as a
residency in urology at the Squier Urological Clinic, Columbia University. From 1988 to 1990 he was an American Urological
Association (AUA) Scholar focused on identifying molecular markers and urodynamic parameters that herald bladder and
prostate dysfunction.
Dr Kaplan was the Given Foundation Professor of Urology and administrator, as well as vice chairman of the department of
urology, at Columbia University from 1998 to 2005. Fellowship director for female urology and voiding dysfunction from 1995
to 2005 at Columbia and at Weill Cornell Medical College since 2005, Dr Kaplan is also the E. Darracott Vaughan Jr. Professor of
Urology and chief, Institute for Bladder and Prostate Health at Weill Cornell Medical College, and director, Iris Cantor Men’s
Health Center at New York Presbyterian Hospital. He is a serial entrepreneur and founder of Medidata Solutions Inc., a publicly
held corporation and one of the premier electronic data capture companies in the world; Medivizor, Inc., a medical informatics
platform; and Blabbelon, a novel voice over Internet protocol platform.
Dr Kaplan is a diplomate of the American Board of Urology and a fellow of the American College of Surgeons. He is a
recognized authority on the study of benign diseases of the prostate and on the association of metabolic factors and voiding
dysfunction and female urology. He has published more than 780 articles and 170 abstracts, and has made over 335
presentations in more than 35 countries. The coauthor of 5 books, he is on the editorial boards of Urology, Journal of Urology,
and Urology Times.
Dr Kaplan is a member of more than 30 professional organizations, has been awarded 5 National Institutes of Health grants,
and has received over 13 million dollars in research funding. He was awarded the John K. Lattimer Award for Lifetime
Achievement in Urology by the National Kidney Foundation. Most recently, he chaired the National Institute of Diabetes and
Digestive and Kidney Diseases’ Prostate Strategic Planning Committee and the BPH/Prostatitis section of the AUA Core
Curriculum.
Faculty Financial Disclosure Statements
The presenting faculty reports the following:
Matt T. Rosenberg, MD, is a consultant for Astellas Pharma US, Inc., Ferring Pharmaceuticals, Inc., Horizon Pharma, Inc., Eli Lilly
and Company, and Pfizer Inc.; he is also a member of the speakers bureau for Astellas Pharma US, Inc., Forest Laboratories, Inc.,
Horizon Pharma, Inc., Ortho-McNeil-Janssen Pharmaceuticals, Inc., and Pfizer Inc.
Session 5
David R. Staskin, MD, is a consultant for Allergan, Inc., AltheRx Pharmaceuticals, Endo Pharmaceuticals Inc./American Systems.,
Takeda Pharmaceuticals U.S.A., Inc., and Theravida, Inc.; he is also a member of the speakers bureau for Allergan, Inc., and Endo
Pharmaceuticals Inc./American Medical Systems.
Steven A. Kaplan, MD, has no financial relationships to disclose.
Education Partner Financial Disclosure Statement
The content collaborators at Integritas Communications have reported the following:
Jim Kappler, PhD, has no financial relationships to disclose.
Suggested Reading List
Crawford ED, Wilson SS, McConnell JD, et al; for the MTOPS RESEARCH Group. Baseline factors as predictors of clinical
progression of benign prostatic hyperplasia in men treated with placebo. J Urol. 2006;175:1422-1426.
De Nunzio C, Aronson W, Freedland SJ, et al. The correlation between metabolic syndrome and prostatic diseases. Eur Urol.
2012;61:560-570.
Gacci M, Corona G, Salvi M, et al. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or
in combination with α-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012;61:9941003.
Giuliano F, Ückert S, Maggi M, et al. The mechanism of action of phosphodiesterase type 5 inhibitors in the treatment of lower
urinary tract symptoms related to benign prostatic hyperplasia. Eur Urol. 2013;63:506-516.
Laborde EE, McVary KT. Medical management of lower urinary tract symptoms. Rev Urol. 2009;11(suppl 1):S19-S25.
McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA guideline on the management of benign prostatic hyperplasia
guideline statements graded as a standard of care, a recommendation, or an option address studies published before February
2008. J Urol. 2011;185:1793-1803.
Oelke M, Bachmann A, Descazeaud A, et al. EAU Guidelines on the Treatment and Follow-up of Non-neurogenic Male Lower
Urinary Tract Symptoms Including Benign Prostatic Obstruction. Eur Urol. 2013;64(1):118-140.
Roehrborn CG. Efficacy of α-adrenergic receptor blockers in the treatment of male lower urinary tract symptoms. Rev Urol.
2009;11(suppl 1):S1-S8.
Rosenberg MT, Staskin DR, Kaplan SA, et al. A practical guide to the evaluation and treatment of male lower urinary tract
symptoms in the primary care setting. Int J Clin Pract. 2007;61:1535-1546.
Weight CJ, Kim SP, Jacobson DJ, et al. The effect of benign lower urinary tract symptoms on subsequent prostate cancer
testing and diagnosis. Eur Urol. 2013;63:1021-1027.
Session 5
Presenter Disclosure Information
SESSION 5
The following relationships exist related to this presentation:
2:30–4pm
► Steven A. Kaplan, MD, has no financial relationships to disclose.
► Matt T. Rosenberg, MD, is a consultant for Astellas Pharma US, Inc.,
Ferring Pharmaceuticals, Inc., Horizon Pharma, Inc., Eli Lilly and
Company, and Pfizer Inc.; he is also a member of the speakers
bureau for Astellas Pharma US, Inc., Forest Laboratories, Inc.,
Horizon Pharma, Inc., Ortho-McNeil-Janssen Pharmaceuticals, Inc.,
and Pfizer Inc.
► David R. Staskin, MD, is a consultant for Allergan, Inc., AltheRx
Pharmaceuticals, Endo Pharmaceuticals Inc./American Systems.,
Takeda Pharmaceuticals U.S.A., Inc., and Theravida, Inc.; he is also a
member of the Speakers Bureau for Allergan, Inc., and Endo
Pharmaceuticals Inc./American Medical Systems.
BENIGN PROSTATIC HYPERPLASIA AND
LOWER URINARY TRACT SYMPTOMS:
Individualized Management in Primary Care
SPEAKERS
Steven A. Kaplan, MD (Virtual Presenter)
Matt T. Rosenberg, MD
David R. Staskin, MD
Presenter Disclosure Information
Scientific and Clinical
Insights Into Benign
Prostatic Hyperplasia
and Lower Urinary
Tract Symptoms
Off-Label/Investigational Discussion
►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.
Steven A. Kaplan, MD
E. Darracott Vaughan Jr. Professor of Urology
Chief, Institute for Bladder and Prostate Health
Weill Cornell Medical College
Director, Iris Cantor Men’s Health Center
New York Presbyterian Hospital
New York, New York
Bladder Function
Scientific Primer in BPH-LUTS
Filling, Storage, and Voiding
Key Points
• Normal function
• BPH-related bladder outlet obstruction is mediated by
compression of the urethra by an enlarged prostate and
increased smooth muscle tone around the prostatic urethra
• Medications used to treat BPH-LUTS target these factors
– Storage capacity (300-500 mL)
• Adequate low pressure urinary
storage (bladder)
• Adequate outlet resistance (sphincter)
– α-blockers: block norepinephrine binding to α-1-adrenergic
receptors, promoting smooth muscle relaxation
– 5-ARIs: disrupt DHT production, decreasing prostate cell
proliferation, increasing apoptosis, and reducing prostate volume
– PDE-5 inhibitors: increase NO/cGMP activity and inhibit Rho
kinase activity to reduce smooth muscle tone
– Empty to completion (minimal residual)
• Adequate bladder contraction
• No outlet obstruction
• Abnormal function
– Failure to store or empty
– Voiding frequently in small amounts
• Also may reduce ANS overactivity, local inflammation/ischemia, and
prostatic and smooth muscle cell proliferation
• Uncontrollable urge (urgency) to empty with frequency
– Incomplete emptying
• BPH-LUTS is associated with metabolic syndrome
• Hesitancy, poor stream, feeling of incomplete emptying
– Central obesity, insulin resistance, dyslipidemia, and hypertension
Lukacz ES, et al. Int J Clin Pract. 2011;65(10):1026-1036; Wein AJ. Pathophysiology and categorization of voiding dysfunction.
In: Wein AJ, Kavoussi LR, Novick AC, et al, eds. Campbell-Walsh Urology. 9th ed. Philadelphia, PA: W. B. Saunders/Elsevier; 2007:1973-1985.
5-ARI, 5α-reductase inhibitor; α-blocker, α-adrenergic receptor antagonist; ANS, autonomic nervous system;
cGMP, cyclic guanosine monophosphate; DHT, dihydrotestosterone; NO, nitric oxide; PDE-5, phosphodiesterase type 5.
1
Overlapping Clinical Constructs
Prostate Function
Definitions
• Normal function
BPE: Anatomic increase in
prostate gland size
BPE
Histologic
BPH
– Obstruction of urinary flow
– Sphincteric damage/usually surgical
(“stress incontinence”)
LUTS/
Bother
Urinary Flow Rate
Decreases With Age
Prostate Volume
4-Year Change
From Baseline, %
Median Peak Flow Rate, mL/sec
Progressive Hyperplasia
1
LUTS: Potential clinical
manifestation of these conditions
BOO, bladder outlet obstruction; BPE, benign prostatic enlargement; BPO, benign prostatic obstruction.
Roehrborn CG. Med Clin N Am. 2011;95:87-100.
Wein AJ. Pathophysiology and categorization of voiding dysfunction. In: Wein AJ, Kavoussi LR, Novick AC, et al, eds.
Campbell-Walsh Urology. 9th ed. Philadelphia, PA: W. B. Saunders/Elsevier; 2007:1973-1985.
2
3
A 55-year-old man with a prostate volume of 30 mL and
BPH-LUTS can expect a doubling of prostate size in the next 15 years4
Age, years
CombAT, Combination of Avodart and Tamsulosin; MTOPS, Medical Therapy of Prostate Symptoms;
REDUCE, REduction by DUtasteride of prostate Cancer Events.
1. McConnell JD, et al. N Engl J Med. 2003;349:2387-2398; 2. Roehrborn CG, et al. Urology. 2011;78:641-646.
3. Roehrborn CG, et al. Eur Urol. 2010;57:123-131; 4. Roehrborn CG, et al. J Urol. 2000;163:13-20.
N=2113 randomly selected men 40–79 years of age with no history of prostate surgery, prostate cancer, or other diseases
known to interfere with normal voiding.
Girman CJ, et al. J Urol. 1993;150:887-892.
Case Study
LUTS Evaluations in Men
Robert
An Overview
• 65-year-old African
American man
• Mentions need to
urinate more frequently,
although it is often
– Retired mechanic
difficult to start and his
– Married with 4 children,
several grandchildren
urine flow has
• Visits PCP for follow-up decreased
– States that he expects
about hypertension
– Controlled with
lisinopril 20 mg daily
BOO: All pathophysiologic
compressions of urethra and
bladder outlet that compromise
urinary flow
BPO: Obstruction confirmed by
pressure flow studies or highly
suspected based on flow rates
and prostate size
BOO
• Abnormal function
1
BPH: Histologic stromoglandular
hyperplasia
All Men
>40 Years Old
– Contributes to continence
– Produces fluid for
seminal emission
– Does not obstruct
urinary flow through
the urethra
• Symptom profile
– Categorization
– Severity
– Bother, functional effects
Clinical Interview
Patient History
Physical Exam
to have problems with
urination as he ages
Are bothersome urinary issues a normal part of aging?
•
•
•
•
•
Comorbidities
Medications
Temporal relationship
DRE
General urinary exam
• Sexual function
• Other risk factors
(eg, smoking,
excessive alcohol intake)
• Abdominal exam
• Neurologic exam
Lab Tests
• PSA level
• Urinalysis
Progression Risks
• Factors that suggest symptoms will worsen or
patients may develop serious medical complications
(eg, AUR)
• Blood sugar
DRE, digital rectal exam; PSA, prostate-specific antigen; AUR, acute urinary retention.
Rosenberg MT, et al. Int J Clin Pract. 2007;61:1535-1546; Rosenberg MT, et al. Int J Clin Pract. 2010;64:488-496.
PCP, primary care provider.
2
IPSS
Clinical Interview for Male LUTS
Symptom Categorization
Storage
Voiding
Postmicturition
Frequency
Hesitancy
Dribbling
Poor flow
Incomplete
emptying
Nocturia
Urgency
Intermittency
Urge
Incontinence
Straining to
Start/Continue
Not
at all
<1 in 5
<1 in 2
About
1 in 2
>1 in 2
Almost
always
1. Over the past month, how often have you had a
sensation of not emptying your bladder
completely after you finished urinating?
0
1
2
3
4
5
2. Over the past month, how often have you had to
urinate again less than 2 hours after you finished
urinating?
0
1
2
3
4
5
3. Over the past month, how often have you found
you stopped and started again several times
while urinating?
0
1
2
3
4
5
4. Over the past month, how often have you found
it difficult to postpone urination?
0
1
2
3
4
5
5. Over the past month, how often have you had a
weak urinary stream?
0
1
2
3
4
5
6. Over the past month, how often have you had to
push or strain to begin urination?
0
1
2
3
4
5
Never
1 time
2 times
3 times
4 times
≥5 times
0
1
2
3
4
5
Urinary Symptomsa
7. Over the past month, how many times did you
typically get up to urinate from the time you went
to bed until the time you got up in the morning?
Total for Urinary Symptomsb
8. If you were to spend the rest of
your life with your urinary
condition the way it is now, how
would you feel about that?
Delighted
Pleased
0
1
Mostly
Satisfied
2
Mixed
3
Mostly
Dissatisfied
4
Unhappy Terrible
5
Abrams P, et al. Neurourol Urodyn. 2002;21:167-178; Roehrborn CG. Med Clin North Am. 2011;95:87-100.
Voiding Diary
Consider Co-occurring Issues
Evaluation of Frequency and Volume
Common Comorbidities in BPH-LUTS
• Differentiate among LUTS pathologies
• Alert patients to modifiable
habits and opportunities
for change
• Monitor treatment progress
and efficacy
• Typically record for 3-7 days
–
–
–
–
Voiding frequency and timing
Number and characteristics of incontinence episodes
Fluid intake
Other urinary symptoms
Registry Patients, %
N=6909 untreated or treated men with BPH-LUTS (mean age, 66.0 years).
Kirby M, et al. Int J Clin Pract. 2013;67:606-618; Roehrborn CG, et al. BJU Int. 2007;100:813-819;
Rosenberg MT. Int J Clin Pract. 2013;67:599-600.
Wyman JF, et al. Int J Clin Pract. 2009;63:1177-1191.
BPH-LUTS, Erectile Dysfunction,
and Metabolic Abnormalities
Erectile Function and LUTS Severity
Examine Sexual Function
Common Pathogenetic Mechanisms: BPH-LUTS and Erectile Dysfunction
Functional
Consequences
in Tissues
(corpora cavernosa,
prostate, urethra,
and bladder)
Insulin Resistance
Increased
RhoA–ROCK
Signaling
Autonomic
Hyperactivity
• Reduced function of nerves
and endothelium
• Altered smooth muscle
relaxation or contractility
• Arterial insufficiency, reduced
blood flow, and hypoxia-related
tissue damage
Chronic Inflammation
Better
Erectile
Function
Pelvic
Atherosclerosis
Mean IIEF Erectile
Function Domain
Reduced
NO–cGMP
Signaling
6
AUA-SI, AUA Symptom Index; IPSS, International Prostate Symptom Score; QoL, quality of life.
aThe IPSS differs from the AUA-SI in that it includes 1 QoL question; bUrinary symptom scoring : Mild, 1-7; Moderate, 8-19; Severe, 20-35.
Barry M, et al. J Urol. 1992;148:1549-1557.
BPH-LUTS
Erectile
Dysfunction
Steroid Hormone Changes
Worse
Erectile
Function
Hypertension, Metabolic Syndrome, Diabetes, etc
N=10,636 men who had been sexually active within the last 4 weeks.
IIEF, International Index of Erectile Function.
McVary KT, et al. BJU Int. 2006;97:23-28.
ROCK, Rho-associated protein kinase.
Briganti A, et al. Eur Urol Suppl. 2009;8:865-871; Gacci M, et al. Eur Urol. 2011;60:809-825; Hammarsten J, et al. Nat Rev Urol. 2011;8:483-494;
Kirby M, et al. Int J Clin Pract. 2013;67:606-618; Rosenberg MT. Int J Clin Pract. 2013;67:599-600.
3
LUTS
Severity
LUTS Evaluation
Medication Effects in BPH-LUTS
Medication
Focused Physical Exam
LUTS-Related Effect
Sedatives1
Alcohol, caffeine,
diuretics2
Evaluation
Confusion, secondary incontinence
Diuresis
Calcium-channel blockers1
Angiotensin-converting
enzyme inhibitors1
First-generation
antihistamines4
Cholinesterase inhibitors2
Genitalia exam
Reduce bladder smooth muscle contractility
Meatus, testes, foreskin
Neurologic exam
General mental status, ambulatory
status, motor function
DRE
Rectal tone, nodules, pain,
prostate size, shape, consistency
Induce cough, stress urinary incontinence
Increase outlet resistance
Precipitate urge incontinence
1. Kashvap M, et al. BMC Geriatr. 2013;13:57; 2. Wyman JF, et al. Int J Clin Pract. 2009;63:1177-1191;
3. Gill SS, et al. Arch Intern Med. 2005;165(7):808-813; 4. Wuerstle MC, et al. Arch Intern Med. 2011;171:1680-1682;
5. Peron E, et al. J Gerontol A Biol Sci Med Sci. 2012;67:1373-1378.
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.
Evaluate Risks for
BPH Progression
Lab Testing
• PSA is more accurate
than DRE
– PSA ≥1.5 ng/mL
suggests a prostate
volume >30 mL
75
60
70
65
60
55
50
55
50
45
40
35
TPV
TPV
<31 mL ≥31 mL
30
1
2
3
4
5
6
– Brother died of
prostate cancer
– Worried that his symptoms
suggest prostate cancer
• LUTS workup
Risk of Prostate Biopsy
• Lisinopril 20 mg daily
• Family history
Qmax Qmax
<10.6
≥10.6
mL/sec mL/sec
PVR
PVR
<39 mL ≥39 mL
Risks of Prostate Biopsy or
Cancer Diagnosis
Clinical Workup
– Hypertension
PSA
PSA
<1.6
≥1.6
ng/mL ng/mL
Men With LUTS
Robert
• Medical history
P=0.0008
aBPH progression was defined as ≥4-point increase in AUA-SI score, AUR, incontinence, renal insufficiency, or recurrent UTI.
N=737 men who were randomized to placebo in the MTOPS trial.
PVR, postvoid residual; Qmax, maximum measured urinary flow rate; TPV, total prostate volume; UTI, urinary tract infection.
1. Crawford ED, et al. J Urol. 2006;175:1422-1426; 2. Robert G, et al. Curr Opin Urol. 2011;21:42-48;
3. Roehrborn CG, et al. BJU Int. 2006;97:734-741.
Bosch J, et al. Eur Urol. 2004;46:753-759; Roehrborn C, et al. Urology. 1999;53:581-589;
Roehrborn CG. Int J Impot Res. 2008;20(suppl 3):s19-s26.
– BMI, 29.8 kg/m2
– BP,125/88 mm Hg
P=0.011
Other risk factors: older age, higher baseline IPSS, and history of AUR, metabolic
syndrome, chronic prostatitis, depressive symptoms, or excessive alcohol use2,3
Serum PSA, ng/mL
• Physical exam
P=0.0002
P<0.0001
Incidence of Overall
BPH Progression1
– Full length and anterior
portion of the gland often
not examined
Age
65
Prostate Volume, mL
• DRE tends to
underestimate size of
larger prostates
(Eventsa per 100 Patient-Years)
PSA and Prostate Size
– IPSS, 19 (moderate)
• Frequency
• Poor flow and intermittency
• Strains to urinate
– PSA level, 1.7 ng/mL
– DRE, firm and symmetrically
enlarged with no nodules
– Urinalysis, no abnormalities
• Sexual function
0.5
Risk of Prostate Cancer
α-Agonists4
ß-Blockers5
Tenderness, masses, bladder
distension
Abdominal palpation
Impaired contractility, voiding difficulty,
overflow incontinence
Increased outlet resistance, voiding difficulty
Decreased urethral closure, stress incontinence
Anticholinergics3
Targets
0.4
0.3
Log Rank P<0.048
HR: 1.2; 95% CI, 0.93-1.5
0.2
0.1
0.0
0.0
2.5
5.0
7.5
10
12.5
0.5
0.4
0.3
Log Rank P=0.7
HR: 0.80; 95% CI, 0.54-1.1
0.2
0.1
0.0
0.0
Follow-up, years
– Some trouble over last year
attaining an erection
Moderate/severe LUTSa
Without moderate/
severe LUTS
2.5
5.0
7.5
Prostate cancer diagnosis was not more likely
based on the presence of LUTS alone
What should the PCP tell Robert about the relationship between
BPH-LUTS and prostate cancer?
aModerate/severe LUTS defined as AUA-SI score >7.
CI, confidence interval; HR, hazard ratio.
N=1839 men, aged 40-79 years, from a representative, population-based cohort.
Weight CJ, et al. Eur Urol. 2013;63:1021-1027.
BMI, body mass index; BP, blood pressure.
4
10
Follow-up, years
12.5
Robert
Management Recommendations
Clinical Workup
LUTS in Men
• LUTS workup
• Physical exam
– BMI, 29.8 kg/m2
– BP,125/88 mm Hg
– IPSS, 19 (moderate)
• Medical history
– Hypertension
• Relevant medical history
• Assessment of LUTS
• Severity and bother (eg, AUA-SI)
• Physical exam, including DRE
• Urinalysis
• Serum PSAa
• Frequency/volume chartb
– PSA level, 1.7 ng/mL
– DRE, firm and symmetrically
enlarged with no nodules
– Urinalysis, no abnormalities
• Lisinopril 20 mg daily
• Family history
– Brother died of
prostate cancer
• Sexual function
– Some trouble over last year
attaining an erection
How would you initiate treatment for Robert?
Patients, %
LUTS Cause Little or No Bother
Informed Surveillance
•Monitor symptoms and screen for complications
•Most appropriate for patients without bothersome
symptoms or AUA-SI score ≤7
•Patient voiding diary
•Annual reevaluation
87% of men with mild symptoms had symptom worsening,
whereas 13% had reduced or stabilized symptoms
aClinical progression, worsening of the IPSS to moderate or severe symptoms (IPSS, 8-18 or 19-35) and >2-point increase in IPSS.
N=397 men with mild LUTS suggestive of BOO (IPSS <8).
Djavan B, et al. Urology. 2004;64:1144-1148.
Abrams P, et al. J Urol. 2009;181:1779-1787; McVary KT, et al. J Urol. 2011;185:1793-1803; Oelke M, et al. Eur Urol. 2013;64:118-140.
Management Recommendations
BPH-LUTS Management
Bothersome LUTS in Men
Behavioral Therapies
Recommended Tests
Polyuria
No Polyuria
• Alter modifiable factors
– Drugs
– Fluid and food intake
• Lifestyle advice
Drug Treatment
Polyuria, 24-hour output ≥3 liters
Lifestyle and fluid intake reducedaa
Nocturnal polyuria, ≥33% output at night
Fluid intake reduced, consider other causes
Suspicious DRE
Hematuria
Abnormal PSA
Pain
Infectionc
Palpable bladder
Neurologic disease
a
Recommended Tests
Standard Treatment
•
•
•
•
•
•
•
Informed Surveillance for
Mild BPH-LUTS
LUTS With Little or No Bother
Bothersome LUTS
Bothersome LUTS
Complicated LUTS
aWhen life expectancy is >10 years and diagnosis of prostate cancer may modify management;
bWhen significant nocturia is predominant symptom; cAssess and start treatment before referral.
Abrams P, et al. J Urol. 2009;181:1779-1787; McVary KT, et al. J Urol. 2011;185:1793-1803; Oelke M, et al. Eur Urol. 2013;64:118-140.
Management Recommendations
Predominant Significant
Nocturia

Frequency/Volume Chart
LUTS Cause Little or
No Bother
Recommended Tests
• Frequency
• Poor flow and intermittency
• Strains to urinate
Education and
Reassurance
• Discuss causes of LUTS, including normal prostate and bladder function
• Discuss natural history of BPH-LUTS (lack of link to prostate cancer)
• Suggest daily fluid intake of 1500-2000 mL
Fluid
Management
Relief From
Bothersome
LUTS

Continue
Treatment
− Minor adjustments for climate and activity
− Avoid inadequate or excessive intake based on frequency/volume chart
• Restrict fluids when symptoms are inconvenient (long journeys, prior to bedtime)
Caffeine and
Alcohol
• Avoid caffeine (eg, substitute decaffeinated or noncaffeinated drinks)
• Avoid alcohol in the evening if nocturia is bothersome
Concurrent
Medication
• Adjust dose timing to improve LUTS at times of greatest inconvenience
• Substitute antihypertensive diuretics with alternatives with fewer urinary effects
Toileting and
Bladder
Retraining
• Advise men to double-void
• Advise urethral milking for men with postmicturition dribble
• Advise bladder retraining
• Use distraction techniques to increase the minimum between-void time to 3 hours
(daytime) and/or the minimum voided volume to 200-400 mL (daytime)
Miscellaneous
• Avoid constipation in men with LUTS
Failure
Detailed
Management
aAdvise
patients with symptoms to aim for a urine output of about 1 L/24 hours.
Abrams P, et al. J Urol. 2009;181:1779-1787; McVary KT, et al. J Urol. 2011;185:1793-1803; Oelke M, et al. Eur Urol. 2013;64:118-140.
− Discuss with PCP
− Predetermined mind exercise, perineal pressure, or pelvic floor exercises
− Urge to void should be suppressed for 1 min, then 5 min, then 10 min, etc
− Use frequency/volume charts to monitor progress
Yap T, et al. Curr Opin Urol. 2010;20:20-27.
5
Physical Activity and
the Risk of BPH or LUTS
Moderatea
Source
BPH-LUTS Management
Pharmacologic Therapy
Vigorousa
Minimum Duration
for Clinical Effect
Common Side Effects
α-Blockers
Selective
(eg, tamsulosin, silodosin)
Nonselective
(eg, alfuzosin, terazosin,
doxazosin)
2-4 weeks
Erectile dysfunction, abnormal ejaculation,
dizziness/syncope, hypotension, fatigue,
nasal congestion, headache, dry mouth,
dry eye
Del Maso et al, 2006
5-ARIs
(eg, finasteride, dutasteride)
2-6 months
Erectile dysfunction, abnormal ejaculation,
gynecomastia, decreased PSA level
Rohrmann et al, 2005
PDE-5 Inhibitors
(eg, tadalafil)
4 weeks
Headache, indigestion, back pain, flushing,
nasal congestion
Antimuscarinic agents
Selective
(eg, darifenacin, solifenacin)
Nonselective
(eg, tolterodine, trospium,
oxybutynin, fesoterodine)
12 weeks
Constipation, dyspepsia, dry mouth, dry
eyes, headache
2-6 months
Erectile dysfunction, abnormal ejaculation,
gynecomastia, dizziness, hypotension,
headache, decreased PSA level
Medication Class
Gann et al, 1995
Platz et al, 1998
Meigs et al, 2001
Lacey et al, 2001
Hong et al, 2006
Rohrmann et al, 2006
Combined
P=0.005
0.19
P=0.006
2.0
0.74
95% CI, 0.60-0.92
Odds Ratios
0.18
0.74
95% CI, 0.59-0.92
3.1
Dual-drug products
Dutasteride–tamsulosin
aAfter
stratifying physical activity into low, moderate, and vigorous levels, groups were compared to a sedentary reference group.
N=35,675 men with BPH-LUTS from 8 studies.
Parsons JK, Kashefi C. Eur Urol. 2008;53(6):1228-1235.
Sarma AV, et al. N Engl J Med. 2012;367:248-257.
Robert
Improving Patient Adherence
Treatment and Follow-up
• Advised on fluid intake, increased physical
activity, and bladder training
• Alfuzosin 10 mg daily
• 1-month follow-up
• Patient adherence and satisfaction reflect perceived
treatment efficacy and side effects
– Choose agents with fewer side effects
• Consider online patient education about BPH symptoms,
treatments, and complications
• Optimize the provider-patient relationship
– IPSS, 15 (moderate)
– Understand effects of social and demographic parameters
– For watchful waiting, discuss monitoring parameters and
behavioral changes in detail
– For pharmacotherapy, discuss side effect profiles
– For more invasive therapy, discuss recovery times, risks, and
complications
• Previous score, 18 (moderate)
– Reports little change in fluid intake and occasionally
forgetting to take his medication
What can be done to improve Robert’s adherence to
the PCP’s treatment recommendations?
DeCastro J, et al. Am J Med. 2008;121:S27-S33.
Detailed Management
Robert
Persistent, Bothersome BPH-LUTS
Treatment Tailoring
• Physical exam
– BMI, 29.8 kg/m2
– BP,125/88 mm Hg
• Medical history
– Hypertension
• Lisinopril 20 mg daily
• Family history
– Brother died of
prostate cancer
• LUTS workup
OAB
(Storage Symptoms)
No Evidence of BOO
– IPSS, 15 (moderate)
• Frequency
• Poor flow and intermittency
• Strains to urinate
• Lifestyle
Intervention
• Behavioral Therapy
• Antimuscarinics
– PSA level, 1.7 ng/mL
– DRE, firm and symmetrically
enlarged with no nodules
– Urinalysis, no abnormalities
Failure
• Sexual function
– Some trouble over last year
attaining an erection
Reassess and
Consider Invasive
Therapy for OAB
Is Robert a candidate for combination therapy?
Which combinations?
aPSA
Recommended Tests
Evidence of BOO
• Flow Rate Recording
• PVR
• Discuss Treatment Options
• Shared Decision
MIST or
Surgery Options
Select Monotherapy or
Combination Therapy
Medical
Therapy
Option
• Symptom profile
− Severity
− Predominant BOO vs
Mixed OAB/BOO
• Prostate size
• PSA levela
• Comorbidities
<1.5 ng/mL suggests small gland; PSA ≥1.5 ng/mL suggests large gland.
MIST, minimally invasive surgical treatment; OAB, overactive bladder.
Abrams P, et al. J Urol. 2009;181:1779-1787; McVary KT, et al. J Urol. 2011;185:1793-1803;
Oelke M, et al. Eur Urol. 2013;64:118-140.
6
Optional Tests
• Validated Questionnaires
• Frequency/Volume Chart
Combination Therapy
Combination Therapy
CombAT Study
RRR=65.8%
(54.7%, 74.1%)
25
RRR=19.6%
(-10.9%, 41.7%)
Placebo
20
Finasteride (P=0.002)
15
10
Doxazosin (P<0.001)
5
Combination therapy (P<0.001)
0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
RRR=67.6%
(52.7%, 77.8%)
RRR=70.6%
(57.7%, 79.5%)
RRR=18.3%
(-27.0%, 47.4%)
RRR=31.1%
(-4.0%, 54.4%)
RRR=44.1%
(33.6%, 53.0%)
RRR=31.2%
(17.7%, 42.5%)
Incidence, %
Cumulative Incidence of
Progressiona, %
MTOPS Study
5.5
Years
• Compared with placebo, doxazosin (α-blocker) or finasteride (5-ARI)
reduced the risk of clinical progression by 39% or 34%, respectively
• Compared with placebo, combination therapy reduced the risk of
clinical progression by 66%
• Combination therapy reduced the relative risk of AUR or BPH-related surgery
− 65.8% compared with tamsulosin (α-blocker) monotherapy
− 19.6% compared with dutasteride (5-ARI) monotherapy
aProgression
defined as an increase of ≥4 points vs baseline in the AUA-SI score, AUR, urinary incontinence, renal insufficiency, or
recurrent UTI.
N=3047 men ≥50 years old with AUA-SI scores between 8 and 35, Qmax between 4 and 15 mL/sec, and voided volumes ≥125 mL.
McConnell JD, et al. N Engl J Med. 2003;349:2387-2398.
N=4844 men ≥50 years old with BPH, IPSS ≥12, prostate volume ≥30 cm3, PSA levels between 1.5 and 10 ng/mL, Qmax >5 and ≤15 mL/s,
and a minimum voided volume ≥125 mL.
RRR, reduction in relative risk.
Roehrborn CG. Eur Urol. 2010;57:123-131.
PDE-5 Inhibitors and α-Blockers
Early vs Delayed Combinations
5-ARI and -Blocker
Clinical
Progressiona
OR=1.70
All Patients
Patients with PSA values
Patients with 1.5< PSA value <10
Source
OR=1.82
All Patients
Patients with PSA values
Patients with 1.5< PSA value <10
OR=1.82
All Patients
Patients with PSA values
Patients with 1.5< PSA value <10
OR=1.75
Surgery
Total Costs
All Patients
Patients with PSA values
Patients with 1.5< PSA value <10
-6 -4 -2
OR=2.50
0
2
IIEF Score
Mean Differences
Qmax
Mean Differences
0 2 4 6 8 1012
-2
0
2
4
6
Kaplan et al, 2007
OR=1.54
OR=1.96
Bechara et al, 2008
Liguori et al, 2009
OR=3.45
Tuncel et al, 2009
OR=1.79
Gacci et al, 2012
OR=1.75
Overall
OR=2.63
1.0
2.0
3.0
4.0
5.0
6.0
7.0
Better Outcomes With Early
Combination Therapyc
α-blocker
+ PDE-5 inhibitor
aClinical
progression, defined as the occurrence of AUR or prostate surgery during the 12 months after first prescription fill.
bDelayed combination therapy, initiation of a 5-ARI >30 days and <180 days after initial α-blocker treatment.
cEarly combination therapy, initiation of an α-blocker and a 5-ARI on the same day, or a 5-ARI within 30 days of initial α-blocker treatment
OR, odds ratio.
N=13,551 men ≥50 years of age and treated for BPH-LUTS with a 5-ARI and an α-blocker.
Morlock R, et al. Clin Ther. 2013;35:624-633.
α-blocker
alone
α-blocker
+ PDE-5 inhibitor
α-blocker
α-blocker
alone + PDE-5 inhibitor
Compared with α-blockers alone, the combination regimens significantly
improved IPSS (P=0.05), IIEF scores (P<0.0001), and Qmax (P<0.0001)
These studies examined the PDE-5 inhibitors tadalafil, sildenafil, and vardenafil, and the α-blockers alfuzosin and tamsulosin.
Gacci M, et al. Eur Urol. 2012;61:994-1003.
Robert
PDE-5 Inhibitors
Treatment Tailoring
Pharmacokinetics
Parameters
• LUTS workup
– IPSS, 15 (moderate)
• Frequency
• Poor flow and intermittency
• Strains to urinate
–
–
–
–
IPSS
Mean Differences
OR=2.33
AUR
0.0
Better Outcomes With Delayed
Combination Therapyb
Effects on BPH-LUTS, Erectile Dysfunction,
and Flow Rate
PSA level, 1.7 ng/mL
DRE, firm and symmetrically enlarged with no nodules
Alfuzosin 10 mg daily
Self-report of some erectile dysfunction
• The PCP considers adding a 5-ARI or PDE-5 inhibitor to
the treatment regimen
Available doses, mg
Tmax, hours
Sildenafil1
25, 50, 100
1
4
Vardenafil2
5, 10, 20
1
4-5
17.5
Tadalafil3
2.5, 5, 10, 20
2
Avanafil4
50, 100, 200
0.5-0.75
5
Lodenafil5
NA in USa
2
2.11
Udenafil6
NA in USa
1-1.5
11-13
Lipids (high fat meals) and alcohol delay absorption but increase bioavailability.
aLodenafil and udenafil are not approved by the US Food and Drug Administration.
NA, not available; T½, half-life; Tmax, time required to achieve maximum concentration.
1. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020895s036lbl.pdf);
2. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021400s011lbl.pdf);
3. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021368s012lbl.pdf);
4. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202276s001lbl.pdf);
5. De Nucci G, et al. BMC Pharmacology. 2007;7(suppl 1):P13; 6. Zhao C, et al. Eur Urol. 2011;60:380-387.
If a PDE-5 inhibitor is prescribed,
how should it be dosed?
7
T½, hours
Tadalafil in BPH-LUTS
Adverse Events With Tadalafil
Once-Daily Dosing
Once-Daily vs On-Demand Dosing
5 mg
Once Dailya
N=238
5/10/20 mg
On Demandb
N=1173
Headache
2.1%
15.8%
Dyspepsia
3.8%
11.8%
Nasopharyngitis
5.9%
11.4%
Back pain
5.0%
8.2%
Influenza-like illness
2.5%
3.2%
Discontinuation due to
adverse events possibly
related to the study drug
0.8%
3.1%
Total IPSS Change
From Baseline
IPSS-HRQoL Change
From Baseline
Adverse Event
N=427 men who completed a 12-week, placebo-controlled, dose-finding study assessing once-daily tadalafil for BPH-LUTS.
HRQoL, health-related quality of life.
Donatucci CF, et al. BJU Int. 2011;107:1110-1116.
a24-month
extension trial of tadalafil 5 mg once daily for erectile dysfunction.
24-month extension trial data from five 8- or 12-week studies examining on-demand tadalafil for erectile dysfunction.
Montorsi F, et al. Eur Urol. 2004;45:339-344; Porst H, et al. J Sex Med. 2008;5;2160-2169.
bPooled
Robert
Robert
Treatment Tailoring
Alternative Presentations
• LUTS workup
• Physical exam
– IPSS, 15 (moderate)
• Poor flow, intermittency, strains to urinate
–
–
–
–
• LUTS work-up
– BMI, 29.8 kg/m2
– BP,125/88 mm Hg
PSA level, 1.7 ng/mL
DRE, firm and symmetrically enlarged with no nodules
Alfuzosin 10 mg daily
Self-report of some erectile dysfunction
• Medical history
– Hypertension
• Lisinopril 20 mg daily
• Family history
• The PCP decides to adjust the treatment regimen
– Brother died of
prostate cancer
– IPSS, 19 (moderate)
– DRE, firm and symmetrically
enlarged with no nodules
– Urinalysis, no abnormalities
• Sexual function
– Some trouble over last year
attaining an erection
How should management change if the DRE revealed a prostate
volume of 50 mL with a PSA level of 4.6 ng/mL?
What would be your recommended approach to
tailoring treatment?
What would you do if Robert’s symptoms were refractory to
treatment with an α-blocker together with a 5-ARI?
Red Flags:
Consider Urologist Referral
Conclusions
Presence of LUTS associated with results of DRE
suggesting prostate cancer
• BPH-LUTS is a progressive condition characterized by
storage, voiding, and postmicturition symptoms
• Common comorbidities of BPH-LUTS include
hypertension, metabolic syndrome, and erectile
dysfunction
Hematuria
Abnormal PSA levels
– These conditions are pathogenically linked
Recurrent UTI
• Effective medical management of BPH-LUTS often
requires behavioral modifications and pharmacotherapy
• In select patients, multidrug therapy can more effectively
reduce BPH-LUTS and risks of disease progression
compared with monotherapy
Palpable bladder
History/risk of urethral stricture
Neurologic disease raising likelihood of primary
bladder disorder
McVary KT, et al. J Urol. 2011;185:1793-1803.
8
Build-a-Case
Question #1
?
Which of the following patient characteristics
should be included in the case study?
Build-a-Case
1. Mild hepatic impairment due to a history of
excessive alcohol intake
Steven A. Kaplan, MD
2. Disturbed sleep and daytime fatigue
E. Darracott Vaughan Jr. Professor of Urology
Chief, Institute for Bladder and Prostate Health
Weill Cornell Medical College
Director, Iris Cantor Men’s Health Center
New York Presbyterian Hospital
New York, New York
3. A large waist circumference
Build-a-Case
Build-a-Case
Joseph: Patient Background
Joseph: Medical History
• 65-year-old Caucasian man
• Dyslipidemia
– Retired 10 years ago
– Lives with wife of 40 years
– Simvastatin 40 mg daily
• Takes longer to urinate
• Presents to his PCP
• Reports feeling somewhat tired during
the day
Additional Considerations
in BPH-LUTS
Alcohol Use, Hepatic Impairment
How does the fact that Joseph has
mild hepatic impairment due to a
history of excessive alcohol intake
affect your approach to patient
assessment or treatment?
• Prescribing considerations for patients with mild,
moderate, or severe hepatic impairment
– α-Blockers are not recommended in patients with
severe hepatic impairment1-4
• No dose adjustment required for silodosin or tamsulosin in
patients with mild or moderate hepatic impairment
– Effects of hepatic impairment on finasteride and
dutasteride have not been studied5,6
• These agents are metabolized extensively in the liver, and
caution is required for individuals with abnormal liver function
1. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019668s021lbl.pdf);
2. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020579s027lbl.pdf);
3. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022206s006lbl.pdf);
4. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021287s011lbl.pdf);
5. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021319s023s025lbl.pdf);
6. See Drugs@FDA (http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020180s037lbl.pdf).
9
Additional Considerations
in BPH-LUTS
Disturbed Sleep, Daytime Fatigue
How does the fact that Joseph
complains of disturbed sleep
and daytime fatigue affect
your approach to patient
assessment or treatment?
• Nocturia increases risk of falls and hip fractures in
older individuals1
• CAMUS trial2
– Men with LUTS and smaller prostates and/or lower
PVR volumes were at greatest risk for sleep problems
– Data suggest that systemic and/or nonprostatic factors
contribute to poor sleep in these patients
• Lack of studies evaluating effects of BPH-LUTS
medications on sleep parameters3
CAMUS, Complementary and Alternative Medicine for Urological Symptoms.
1. Asplund R. BJU Int. 1999;84:297-301; 2. Helfand BT, et al. J Urol. 2011;185:2223-2228; 3. Cai T, et al. BJU Int. 2006;98:799-805.
Additional Considerations
in BPH-LUTS
Large Waist Circumference
• Increased waist circumference is associated
with worsened voiding1
• Mechanistic relationships between obesity,
erectile dysfunction, and BPH-LUTS
How does the fact that Joseph has
a large waist circumference
affect your approach to patient
assessment and treatment?
– Obese men have relatively low testosterone/high
estrogen hormonal profiles2,3
• May increase risks of BPH-LUTS and erectile dysfunction
– Hyperinsulinemia may induce prostate growth2,3
• Lifestyle modifications for obesity
– How long until erectile function improves?
– How long until BPH-LUTS improve?
1. Lee RK, et al. BJU Int. 2012;110:540-545; 2. Hammarsten J, et al. Prostate Cancer Prostatic Dis. 2009;12:160-165;
3. St Sauver JL, et al. Am J Epidemiol. 2011;173:787-796.
Build-a-Case
Build-a-Case
Joseph: Patient Workup
Joseph: Patient Workup
• Urinary symptoms
•
•
•
•
•
– Terminal dribbling
– Weak urine stream
– Urinates 2 or 3 times each night
• Physical exam
– Abdomen is soft
– No signs of malignancy
BMI, 29.9 kg/m2
BP, 135/85 mm Hg
Does not smoke or drink alcohol
Urinalysis negative
Some trouble achieving an erection
BMI, body mass index; BP, blood pressure.
10
Joseph
Build-a-Case
Potential Evaluation Techniques
Joseph: Additional Workup
• DRE1,2
– Rule out induration, mass, or nodularity indicative of neoplasm or
inflammatory process
– Anal sphincter tone assessed to rule out neurologic causes
• DRE
– Nontender, enlarged, normally shaped
prostate
– No nodules
• PSA testing1,2
– Compared with DRE, PSA better estimates prostate volume
– High PSA levels suggest higher risk of disease progression3
– PSA levels can guide treatment selection and follow-up frequency
• PSA level, 1.7 ng/mL
• Other lab tests normal
• Diagnosis of LUTS secondary to BPH
• Serum creatinine measurement2,4
– Screening test for obstructive uropathy
– Serum creatinine test can be useful in patients with
high PVR volumes
– Guidelines no longer recommend routine creatinine measurement
1. Roehrborn CG. Med Clin North Am. 2011;95:87-100; 2.Tabatabaei S, et al. Curr Urol Rep. 2012;13:474-481;
3. Crawford ED, et al. J Urol. 2006;175:1422-1426; 4. McVary KT, et al. J Urol. 2011;185:1793-1803.
Additional Considerations
for BPH-LUTS
Diabetes
Diabetes-Related Insulin Resistance,
Hyperinsulinemia and/or Hyperglycemia1,2
How does the presence of
comorbid type 2 diabetes affect
your treatment choices for Joseph?
Sympathetic
Overactivity
IGF
Activity
Increase in Prostate
Smooth Muscle Tone
Alteration in Sex
Steroid Metabolism
Inflammation
Hyperplasia/
Prostate Growth
BPH-LUTS
• Intensive glycemic control did not reduce the risk or
severity of LUTS in men with type 1 diabetes
• Precise mechanisms underlying associations between
diabetes and nocturia are unclear
IGF, insulin-like growth factor.
1. Parsons JK. Curr Opin Urol. 2011;21:1-4; 2. Sarma AV, et al. J Urol. 2009;182(suppl 6):S32-S37;
3. Van Den Eeden SK, et al. Diabetes Care. 2009;32:664-670.
Additional Considerations
in BPH-LUTS
Hypertension
• Risk of hypertension increases by 5.3%
and 5.0% with each year of age and
IPSS point, respectively1
• ALLHAT1,2
How does the presence of
controlled hypertension affect your
treatment choices for Joseph?
– Compared chlorthalidone (thiazide diuretic)
and doxazosin (α-blocker) to prevent new
onset of heart failure
– Doxazosin was associated with a 2-fold higher risk
of congestive heart failure among high-risk
hypertensive patients
ALLHAT, Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial.
1. Einhorn PT, et al. Am Heart J. 2007;153:42-53; 2. Rossitto G, et al. Cleve Clin J Med. 2010;77:884-888.
11
Additional Considerations
in BPH-LUTS
Chronic Pelvic Pain Syndrome
• Chronic pelvic pain syndrome often precedes
BPH-LUTS
How does the presence of chronic
pelvic pain syndrome affect your
treatment choices for Joseph?
– Chronic pelvic pain syndrome commonly develops
in patients between 35 and 50 years of age1
– BPH-LUTS commonly affects men aged ≥60 years2
• MTOPS and REDUCE trials revealed
associations between histologic prostate
inflammation and:
– Prostate enlargement3,4
– LUTS severity3,4
1. Collins MM, et al. J Urol. 1998;159:1224-1228; 2. Roehrborn CG. Rev Urol. 2005;7(suppl 9):S3-S14;
3. Nickel JC, et al. Eur Urol. 2008;54:1379-1384; 4. Verhamme KM, et al. Eur Urol. 2002;42:323-328.
Build-a-Case
Build-a-Case
Joseph: Initial Treatment
Joseph: Follow-up
• Silodosin 8 mg daily
• Increased physical activity
• Modified fluid intake
• More physical activity
• Adherent to silodosin
• Little symptomatic improvement
– Nocturia
– Weak urinary stream
– Voiding up to 10 times daily
• Sexual symptoms worsened
Joseph
Concluding Comments
• α-Blockers and 5-ARIs, alone or in combination,
may precipitate a number of adverse effects
– Dizziness, hypotension, sexual dysfunction
ASK THE EXPERTS:
• Compared with more uroselective medications,
nonuroselective α-blockers produce fewer effects
on ejaculation
• PDE-5 inhibitors are safe and effective in combination with
or instead of α-blockers for patients with BPH-LUTS ±
erectile dysfunction
• Data supporting antimuscarinic monotherapy are lacking
QUESTION & ANSWER
SESSION
– Combination regimens with α-blockers can reduce storage
symptoms
– Baseline PVR should be checked before initiating therapy
McVary KT, et al. J Urol. 2011;185:1793-1803; Tabatabaei S, et al. Curr Urol Rep. 2012;13:474-481.
12