1. 11
CLINICAL PRACTICE Q&A
A CME PROGRAM FOR MEN’S UROLOGICAL HEALTH
BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS
BPH-LUTS HOME

2. 22
STEERING COMMITTEE
Ghalib Ahmed, MD, CCFP
General Family Practitioner,
Associate Clinical Professor,
Department of Family Practice,
University of Alberta
Gerald Brock, MD, FRCSC
Professor of Surgery,
Urology Program Director,
University of Western Ontario
Chair Office of Education,
Canadian Urology Association
Lydia Hatcher, MD, CCFP, FCFP
Clinical Associate,
Professor of Family Medicine,
Memorial University of
Newfoundland
Murray Awde, MD, CCFP, FCFP
Clinical Professor of Family Medicine,
University of Western Ontario
Serge Carrier, MD, FRCSC
Associate Professor,
Division of Urology,
Department of Surgery,
McGill University
Jay Lee, MD, FRCSC
Clinical Assistant Professor,
Division of Urology,
Department of Surgery,
University of Calgary
Anthony Bella, MD, FRCSC
Greta and John Hansen Chair in Men's
Health Research,
Assistant Professor of Urology,
Department of Surgery,
Associate Scientist, Neuroscience,
University of Ottawa
Stacy Elliott, MD
Director, BC Center for Sexual Medicine,
Sexual Medicine Consultant,
Men’s Health Initiative,
Vancouver Coastal Health
Clinical Professor, Departments of
Psychiatry and Urologic Sciences,
University of British Columbia
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3. 33
STEERING COMMITTEE DISCLOSURES
Ghalib Ahmed, MD, CCFP
• Grants/Research Support: AstraZeneca, Bristol-Myers Squibb,
Pfizer, Servier, Sunovion
• Speaker’s Bureau/Honoraria: Abbott, AstraZeneca, Eli Lilly,
Lundbeck, Merck, Pfizer, Shire
• Consulting Fees: Abbott, AstraZeneca, Bayer, Boehringer
Ingelheim, Bristol-Myers Squibb, Eli Lilly, Lundbeck, Merck, Pfizer
Murray Awde, MD, CCFP, FCFP
• Grants/Research Support: Astellas, Bristol-Myers Squibb,
Boehringer Ingelheim, Merck, Novartis, Otsuka, Purdue
Pharmaceuticals
• Speaker’s Bureau/Honoraria: Abbott, AstraZeneca, Bayer, LEO,
Takeda, Nycomed
• Consulting Fees: Boehringer Ingelheim, Bristol-Myers Squibb,
Eli Lilly, Merck, Novartis, Novo Nordisk, Pfizer
Anthony Bella, MD, FRCSC
• Grants/Research Support: Acorda Therapeutics, Canadian
Foundation for Innovation, Canadian Male Sexual Health Council,
Northeastern Section American Urological Association
• Speaker’s Bureau/Honoraria: Abbott, American Medical Systems,
Bayer, Coloplast, Eli Lilly, Pfizer
Gerald Brock, MD, FRCSC
• Grants/Research Support: American Medical Systems, Eli Lilly,
GlaxoSmithKline, Pfizer
• Speaker’s Bureau/Honoraria: American Medical Systems, Bayer,
Coloplast, Eli Lilly, GlaxoSmithKline, Pfizer
• Consulting Fees: Bayer, Eli Lilly, GlaxoSmithKline, Pfizer
Serge Carrier, MD, FRCSC
• Grants/Research Support: Bayer, Eli Lilly, Pfizer
• Speaker’s Bureau/Honoraria: Abbott, Bayer, Eli Lilly, Pfizer
Stacy Elliott, MD
• Speaker’s Bureau/Honoraria: Abbott, Bayer, Eli Lilly, Pfizer
• Consulting Fees: Abbott, Bayer, Eli Lilly, Pfizer
Lydia Hatcher, MD, CCFP, FCFP
• Grants/Research Support: Servier
• Speaker’s Bureau/Honoraria: AstraZeneca, Boehringer Ingelheim,
Eli Lilly, Janssen-Ortho, Merck, Nycomed, Pfizer, Purdue
Pharmaceuticals, Takeda, Valeant
• Consulting Fees: AstraZeneca
Jay Lee MD, FRCSC
• Speaker’s Bureau/Honoraria: Abbott, Bayer, Eli Lilly,
GlaxoSmithKline, Pfizer
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4. 4
4
SPEAKER DISCLOSURES
• Faculty: [Speaker’s name]
•
•
•
•
Grants/Research Support:
Speaker’s Bureau/Honoraria:
Consulting Fees:
Other:
HOME

5. 5
5
DISCLOSURE OF COMMERCIAL SUPPORT
• This program has received financial support from Eli Lilly Canada Inc
in the form of an educational grant
• This program has received in-kind support from Eli Lilly Canada Inc
in the form of logistical support.
• Potential for conflict(s) of interest:
• [Speaker/Faculty name] has received funding Eli Lilly Canada Inc.
• Eli Lilly markets tadalafil, a product that will be discussed in this program.
HOME

6. 6
6
MITIGATING POTENTIAL BIAS
• All content in this presentation has been developed, reviewed and
approved by the Steering Committee
• All the recommendations involving clinical medicine are based on
evidence from well-designed clinical trials published in peerreviewed journals
HOME

7. 77
BPH-LUTS
• The goal of this module is to address common questions in the area
of BPH-LUTS
• Benign prostatic hyperplasia is the histological pattern of the prostate, characterized
by proliferation of smooth muscle and epithelial cells within the prostatic transition
zone. This may lead to prostatic enlargement.
• Lower urinary tract symptoms refer to storage and/or voiding disturbances.
• BPH-LUTS refers to bothersome lower urinary tract symptoms
linked to the prostate
BPH: benign prostatic hyperplasia; LUTS: lower urinary tract symptoms.
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; 2. Abrams et al. J Urol. 2009; 181:1779-87.
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BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS
1
How should I
evaluate a patient
with BPH-LUTS?
3
How do I decide which
agent to prescribe for
BPH-LUTS?
5
2
Is there evidence of a
relationship between
BPH-LUTS and ED?
4
When should I refer a
patient to a urologist?
How should I follow-up
with a BPH-LUTS patient?
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BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS
1
How should I evaluate
a patient with BPH-LUTS?
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10
LEARNING OBJECTIVES
• After completing this question participants will be able to:
• Identify diagnostic assessments for BPH-LUTS and integrate these into clinical
practice
• Evaluate the utility of PSA testing and recognize the CUA’s position on testing
• Distinguish the signs and symptoms of OAB from BPH-LUTS
CUA: Canadian Urological Association; OAB: overactive bladder; PSA: prostate-specific antigen.
BPH-LUTS HOME

11. HOW SHOULD I EVALUATE A
PATIENT WITH BPH-LUTS?
•
•
•
•
•
11
11
Medical history
Directed physical exam
Urinalysis
PSA testing
Symptom assessment
PSA: prostate-specific antigen.
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12
MEDICAL HISTORY
• Medical history should assess:1,2
•
•
•
•
•
•
Nature and duration of symptoms
Fluid intake – amount and types of fluid
Comorbid conditions
Prior and current illness
Prior surgery and trauma
Current medications
Do you routinely ask about sexual
function when evaluating a
patient for LUTS?
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Abrams et al. J Urol. 2009;181:1779-87.
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13
BPH-LUTS AND ED
• BPH-LUTS and ED are common comorbid conditions
100
% of Patients with
Erectile Problems
90
80
50-59 yrs (n=5,786)
60-69 yrs (n=4,191)
70-79 yrs (n=2,828)
70
60
50
40
30
20
10
0
No symptoms
Mild
Moderate
Severe
Severity of LUTS
1. Rosen et al. Eur Urol. 2003;44:637-49.
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14
DIRECTED PHYSICAL EXAM
• Physical examination for patients with BPH-LUTS:1,2
• MANDATORY EVALUATION – DIGITAL RECTAL EXAM
• Evaluate prostate for size, consistency, shape and abnormalities suggestive of
prostate cancer (such as nodules or asymmetry)
• Assess suprapubic area to rule out bladder distention
• Evaluate overall motor and sensory function of the perineum and lower limbs
especially with a history of stroke or neurologic disease
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Abrams et al. J Urol. 2009;181:1779-87.
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15
URINALYSIS
• Dipstick urinalysis should be performed in all BPH-LUTS patients
to rule out other diagnoses that may cause LUTS:
Urinalysis Result
Possible Diagnosis
• Hematuria
• Kidney stones
• Bladder cancer
• Pyuria or
presence of nitrates
• UTI
• Urethral stricture
• Proteinuria
• Underlying renal disease
• Glucosuria
• Diabetes
Abnormal/borderline urinalysis results should be repeated and/or
followed with a urine culture1
UTI: urinary tract infection.
1. Abrams et al. J Urol. 2009;181:1779-87.
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16
PSA TESTING
Do you currently recommend
PSA testing for your patients
with BPH-LUTS?
PSA: prostate-specific antigen.
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17
WHY PSA TESTING?
PSA can Help Predict Prostate Size
75
Prostate Volume (ml)
60
70
65
60
50
55
50
40
30
1
2
3
4
Serum PSA
5
6
7
ng/mL-1
Adapted from Roehrborn et al. Urology. 1999;53:581-9.
DRE: digital rectal exam; PSA: prostate-specific antigen.
1. Roehrborn et al. Urology. 1999;53:581-9.
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18. PSA CAN IDENTIFY PATIENTS WITH HIGHER RISK
OF RETENTION OR SURGICAL INTERVENTION
Four Year Incidence (%)
26
18
18
Need for BPH-related surgery
Acute urinary retention
24
20
18
14
10
6
2
>0
>1
>2
>3
>4
>5
Baseline PSA Thresholds
>6
>7
>8
PSA: prostate-specific antigen.
1. Roehrborn et al. Urology. 1999;53:473-80.
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19
CUA RECOMMENDATIONS
FOR PSA TESTING
• The CUA position on PSA as a screening test for prostate cancer
DIFFERS from the USPSTF1
• CUA recommends PSA testing be offered to all men ≥50 years of age with a life
expectancy of ≥10 years.
• Canadian guidelines for the management of BPH-LUTS suggest PSA
testing for:2
• Patients who have at least a 10 year life expectancy, and for whom the presence of
prostate cancer would change management
• Patients for whom PSA measurement may change the management of their voiding
symptoms (estimate for prostate volume)
CUA: Canadian Urological Association; PSA: prostate-specific antigen; USPSTF: United States Preventive Services Task Force.
1. CUA position statement on PSA testing. November 2011; 2. Nickel et al. CUAJ. 2010;4:310-6.
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SYMPTOM ASSESSMENT
• Assess the severity of symptoms and degree of bother1
• Evaluate response to treatment
• Validated symptom assessment tools are available:
• International Prostate Symptom Score (IPSS)
• American Urological Association (AUA) symptom score
Click here for more
info on IPSS
• Lower urinary tract symptoms classified as:2
• Storage symptoms
• Voiding symptoms
• Post-micturition symptoms
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Abrams et al. Urology. 2003;61:37-49.
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21
STORAGE (IRRITATIVE) SYMPTOMS
Q
•
•
•
•
•
•
What are the characteristic
storage symptoms?
Frequency
Nocturia
Urgency
Urinary incontinence
Stress incontinence
Urge incontinence
1. Abrams et al. Urology. 2003;61:37-49.
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22
VOIDING (OBSTRUCTIVE) SYMPTOMS
Q
•
•
•
•
•
•
What are the characteristic
voiding symptoms?
Slow stream
Splitting or spraying
Intermittent stream
Hesitancy
Straining
Terminal dribble
1. Abrams et al. Urology. 2003;61:37-49.
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23
POST-MICTURITION SYMPTOMS
Q
What are the characteristic
post-micturition symptoms?
• Feeling of incomplete emptying
• Post-micturition dribble
1. Abrams et al. Urology. 2003;61:37-49.
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24
SYMPTOM BOTHER
LUTS Presentation
Mild Symptoms
Moderate – Severe Symptoms
No Significant Bother
Moderate – Severe Bother
IPSS Quality of Life Assessment2
“If you were to spend the rest of your life with your urinary
condition as is, how would you feel about it?”
IPSS: International Prostate Symptom Score.
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Barry et al. J Urol. 1992;148:1549-57.
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25
OPTIONAL ASSESSMENTS
• Optional assessments for BPH-LUTS include:
•
•
•
•
•
•
Post-void residual
Sexual function questionnaire (i.e. SHIM)2
Serum creatinine
Urine cytology
Uroflow
Voiding diary
Click here for more
info on SHIM
SHIM: Sexual Health Inventory for Men.
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Rosen et al. Int J Imp Res. 1999;11:319-26.
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26
OTHER ASSESSMENTS
(NOT RECOMMENDED)
• Other assessments can be considered, however these are not
recommended for BPH-LUTS:
•
•
•
•
•
•
Cystoscopy
Cytology
Urodynamics
Radiological evaluation of upper urinary tract (CT/MRI)
Prostate ultrasound
Prostate biopsy
CT: computed tomography; MRI: magnetic resonance imaging.
1. Nickel et al. CUAJ. 2010;4:310-6.
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27
DISTINGUISHING BPH-LUTS FROM OAB
Q
How do you distinguish
between BPH-LUTS and OAB?
Typically distinguished by:
• Voiding symptoms
• Failure of standard BPH-LUTS therapy to
resolve symptoms
OAB: overactive bladder.
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28
BPH-LUTS VS. OAB
BPH-LUTS
• Prostate-mediated bladder
voiding obstruction symptoms
• Frequency, nocturia, urgency
• Intermittent stream, straining
• Weak urinary stream
• Sense of incomplete emptying
OAB
• BPH-LUTS medications fail to
resolve storage symptoms
• Urgency (+/- urge incontinence)
• Frequency, nocturia
OAB: overactive bladder.
1. Clemens et al. J Urol. 2007;178:1354-8.
BPH-LUTS HOME

29. PERSISTENT STORAGE SYMPTOMS MAY
BE A SIGN OF OTHER PROBLEMS
29
29
WARNING
Persistent storage symptoms
may be related to other conditions
• Higher risk in smokers and patients with microscopic hematuria
• Storage symptoms secondary to neurologic disease may be more
difficult to treat
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30
TAKE HOME MESSAGES
• Evaluation of BPH-LUTS includes:
• Medical history (including comorbid conditions)
• BPH-LUTS and ED are common comorbid conditions
• Physical exam (with DRE)
• Urinalysis
• PSA testing
• Sensitive marker for prostate volume
• Recommended in patients with BPH-LUTS and a life-expectancy >10 years
• Symptom bother assessment
• OAB is characterized by storage symptoms which persist upon
treatment of BPH-LUTS
DRE: digital rectal exam; ED: erectile dysfunction; OAB: overactive bladder; PSA: prostate-specific antigen.
1. Nickel et al. CUAJ. 2010;4:310-6.
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31
BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS
2
Is there evidence of a
relationship between
BPH-LUTS and ED?
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32
LEARNING OBJECTIVES
• After completing this question participants will be able to:
• Recognize the link between BPH-LUTS and ED and its implications for
treatment
• Assess recent data for PDE5 inhibitors in BPH-LUTS and integrate this new
indication into clinical practice
PDE: phosphodiesterase.
BPH-LUTS HOME

33. IS THERE EVIDENCE OF A RELATIONSHIP
BETWEEN BPH-LUTS AND ED?
33
33
• Epidemiological
• Pathophysiological
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34
EPIDEMIOLOGICAL LINK
BETWEEN BPH-LUTS & ED
% of Patients with
Erection Problems
• Erection problems strongly associated with LUTS (p<0.001)1
100
90
80
70
60
50
40
30
20
10
0
50-59 yrs (n=5,786)
60-69 yrs (n=4,191)
70-79 yrs (n=2,828)
No
symptoms
Mild
Moderate
Severe
Severity of LUTS
1. Rosen et al. Eur Urol. 2003;44:637-49.
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35
CAUSE OF BPH-LUTS
• Original thinking was that BPH-LUTS was the result of:
• Physical obstruction by the prostate
• Contraction of the bladder neck
Mechanisms now implicated in BPH-LUTS:1
• Altered smooth muscle relaxation or contractility
• Reduced blood flow
• Reduced function of nerves and endothelium
1. Gacci et al. Eur Urol. 2011;60:809-25.
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36
LOCALIZATION OF PDE5:
IMPLICATIONS FOR BPH-LUTS
• PDE5 enzyme blocks NO mediated smooth muscle relaxation
• The PDE5 enzyme is found in tissues of the:1
•
•
•
•
Penis
Bladder
Prostate
Urethra
PDE5
NO: nitric oxide; PDE5: phosphodiesterase 5.
1. Fibbi et al. J Sex Med. 2010;7:59-69.
BPH-LUTS HOME

37. SMOOTH MUSCLE CONTRACTION:
IMPLICATIONS FOR BPH-LUTS
37
• PDE5 inhibitor increases:1
• NO, causing smooth muscle
relaxation
• Blood flow to the pelvis and penis
GMP
Smooth
muscle
relaxation
Smooth
muscle
contraction
cGMP
cGMP: cyclic guanosine monophosphate: GMP: guanosine monophosphate; NO: nitric oxide; PDE5: phosphodiesterase 5;
PDE5i: phosphodiesterase 5 inhibitor.
1. Wang. Curr Opin Urol. 2010;20:49-54.
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38. ALL PDE5 INHIBITORS HAVE BEEN
SHOWN TO IMPROVE BPH-LUTS
Sildenafil1*
0
Vardenafil2*
Weeks
6
12
0
-1
8
0
-1
Mean Change
in Symptom Score
Mean Change
in Symptom Score
0
Weeks
4
38
-2
-3
-4
-5
-6
Placebo
Sildenafil
-7
Tadalafil3
0
Mean Change
in Symptom Score
0
-2
Weeks
6
-2
-3
-4
-5
Vardenafil
Placebo
-6
-7
12
Placebo
Tadalafil 5 mg
Tadalafil 20 mg
-4
-6
-8
-10
*Not indicated for the treatment of BPH-LUTS. PDE5: phosphodiesterase 5.
1. McVary et al. J Urol. 2007;177:1071-7; 2. Stief et al. Eur Urol. 2008;53:1236-44.; 3. McVary et al. J Urol. 2007;177:1401-7.
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PDE5 INHIBITORS FOR BPH-LUTS
Study
Description
Length
Effect on LUTS
McVary et al,
2007
• 369 men with LUTS and ED
• Daily sildenafil* vs. placebo
12 weeks
• Significant ↓ IPSS
• Significant ↑ QoL
• ↔ Qmax and Qav
Tuncel et al,
2010
• 60 men with BPH-LUTS
• Sildenafil* (4 days/week) or
tamsulosin or combination
8 weeks
• Improved urinary symptoms with
tamsulosin/combination
• ↑ erectile function with sildenafil/combination
McVary et al,
2007
• 281 men with BPH-LUTS
• Tadalafil once daily
12 weeks
• Significant ↓ IPSS at 6 and 12 weeks
• ↔ Qmax and Qav
Roehrborn et al,
2008
• 886 men with BPH-LUTS
• Daily tadalafil
12 weeks
• Significant improvement in urinary symptoms
Stief et al,
2008
• 222 men with BPH-LUTS
• Vardenafil* twice daily
8 weeks
• Significant improvement in irritative/obstructive
symptoms and general QoL
Gacci et al,
2011
• 60 men with persistent
irritative urinary symptoms
• Vardenafil* + tamsulosin vs.
tamsulosin
12 weeks
• Significant reduction of irritative symptoms with
combined therapy
No change in urinary flow rate with PDE5 inhibitors
*Not indicated for the treatment of BPH-LUTS.
IPSS: International Prostate Symptom Score; Qav: average flow rate; Qmax: maximum flow rate; QoL: quality of life; PDE5: phosphodiesterase 5.
1. Gacci et al. Eur Urol. 2011;60:809-25.
BPH-LUTS HOME

40. REASONS FOR LACK OF LUTS
IMPROVEMENT WITH PDE5I FOR ED
Q
40
In the past, why have patients not
reported improvements in LUTS when
they have used a PDE5 inhibitor for ED?
• Treatment of BPH-LUTS with PDE5 inhibitors requires daily dosing
•
Many patients use PDE5 inhibitors on-demand for ED
• Short-acting PDE5 inhibitors (sildenafil/vardenafil) require TID dosing to
reach appropriate plasma levels
• Only long-acting PDE5 inhibitors are clinically relevant for BPH-LUTS
PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor; TID: three-times daily.
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TADALAFIL 5 MG BUT NOT 2.5 MG IS
EFFECTIVE FOR THE TREATMENT OF BPH-LUTS
Mean Change in Total IPSS Score
from Baseline to Endpoint
PLA Run In
Week - 4
Baseline
Week 0
Placebo
Week 4
0
Week 8
Week 12
TAD 2.5 mg
TAD 5.0 mg
-1
TAD 10.0 mg
-2
TAD 20.0 mg
-3
Clinically meaningful
improvement
-4
-5
-6
-7
-8
-9
Tadalafil 2.5 mg p<0.05 at week 4
Tadalafil 5, 10, and 20 mg p<0.01 for weeks 4, 8, and 12 compared to placebo
IPSS: International Prostate Symptom Score; PLA: placebo; TAD: tadalafil.
1. Roehrborn et al. J Urol. 2008;180:1228-34.
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EFFICACY OF PDE5I’S FOR BPH-LUTS
LS Mean Change from Baseline
in IPSS Total Score
0
Placebo
Tadalafil
Tamsulosin
-1
-2
-3
-4
-5
-6
-7
0
2
4
6
8
10
12
Duration of Treatment (weeks)
IPSS: International Prostate Symptom Score; LS: least squares; PDE5I: phosphodiesterase 5 inhibitor.
1. Oelke et al. Eur Urol. 2012;61:917-25.
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43
TADALAFIL FOR BPH
• On June 28, 2012 Health Canada approved tadalafil for the
treatment of:1
• The signs and symptoms of benign prostatic hyperplasia (BPH)
• Erectile dysfunction (ED) and the signs and symptoms of BPH
1. Cialis Product Monograph. Eli Lilly Canada Inc.
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44
TAKE HOME MESSAGES
• BPH-LUTS and ED often occur together
• Pathophysiological link between BPH-LUTS and ED
•
Suggests a role for the NO/cGMP pathway (which regulates smooth muscle
relaxation)
• PDE5 inhibitors improve smooth muscle relaxation and are an
effective treatment for both ED and BPH-LUTS
• Once daily tadalafil is approved in Canada for the treatment of BPHLUTS
cGMP: cyclic guanosine monophosphate: NO: nitric oxide; PDE5: phosphodiesterase 5.
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45
BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS
3
How do I decide which agent
to prescribe for BPH-LUTS?
BPH-LUTS HOME

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46
LEARNING OBJECTIVES
• After completing this question participants will be able to:
• Evaluate factors that influence treatment decisions for BPH-LUTS
• Assess the pharmacological treatment options for BPH-LUTS, including a
recently approved PDE5 inhibitor
PDE5: phosphodiesterase 5.
BPH-LUTS HOME

47. HOW DO I DECIDE WHICH AGENT TO
PRESCRIBE FOR BPH-LUTS?
47
47
• Symptom severity
• Bother
• Prostate size
Other factors:
• Side effects
• Tolerability
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48
CUA TREATMENT ALGORITHM
LUTS Presentation
Mild Symptoms
Click on the
underlined “criteria”
for a specific focus on
that algorithm stage
Moderate – Severe Symptoms
No Significant Bother
Small Prostate
Large Prostate
Watchful Waiting
Watchful Waiting
or
5-ARI
Small Prostate
Watchful Waiting
Moderate – Severe Bother
Large Prostate
Small Prostate
Large Prostate
Watchful Waiting
or
5-ARI
Alpha-Blocker
or
Surgical Options
Alpha-Blocker
or
5-ARI
or
Combination Therapy
or
Surgical Options
Large prostate is considered to be >30 g
(correlates to a PSA of ≥1.5 ng/mL)2,3
5-ARI: 5-alpha reductase inhibitor; PSA: prostate-specific antigen.
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Barkin J. Can J Urol. 2011;18 Suppl:14-9; 3. Roehrborn et al. Urology. 1999;53:581-9.
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49
ALPHA-BLOCKERS
• Selective antagonist of α1-adrenoceptors located in:
•
•
•
•
•
Prostate
Prostatic capsule
Bladder base
Bladder neck
Prostatic urethra
• Help relax smooth muscle in the bladder neck and prostate; allow
urine to flow more freely
• Selective and non-selective alpha-blockers exist
• Non-selective alpha-blockers are not commonly used for BPH-LUTS
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS.
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50. 50
50
ALPHA-BLOCKER OPTIONS
• First-line options include:1,2
• Selective:
•
• Alfuzosin
• Tamsulosin
• Silodosin
Non-selective:
• Doxazosin
• Terazosin
• Equal clinical effectiveness for LUTS secondary to BPH
• Do not alter the natural progression of the disease
• Choice of agent should depend on comorbidities, side effect profile
and tolerance
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Rapaflo Product Monograph. Watson Laboratories Inc.
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5-ALPHA REDUCTASE INHIBITORS
• Indicated as first-line therapy for men with enlarged prostates: 1,2
• Finasteride  inhibits 5α-reductase Type 2 (prostate)
• Dutasteride  inhibits 5α-reductase Type 1 AND 2 (liver, skin and prostate)
• Blocks the conversion of testosterone to DHT (responsible for
prostate growth)
• Treatment with 5-ARIs reduce:1
•
•
•
•
Prostate size
PSA
Long-term risk of acute urinary retention
Need for surgery
5-ARIs: 5-alpha reductase inhibitors; DHT: dihydrotestosterone; PSA: prostate-specific antigen.
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; 2. Nickel et al. CUAJ. 2010;4:310-6.
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PCPT1
30
25
20
Finasteride
Placebo
15
10
5
0
Overall
mGs 5-6 mGs 7-10 mGs 8-10
Incidence of Prostate Cancer
(%)
Incidence of Prostate Cancer
(%)
5-ARIs AND PROSTATE CANCER
REDUCE2
30
25
20
Dutasteride
Placebo
15
10
5
0
Overall
mGs 5-6
mGs 7-10 mGs 8-10
• Proposed explanations for the increased incidence of high-grade
tumours in 5-ARI arm over placebo:3
• 5-ARIs shrink prostate volume: ↑ likelihood of detecting high-grade disease
• 5-ARIs reduce BPH: ↑ sensitivity of PSA and DRE in detecting disease
5-ARIs: 5-alpha reductase inhibitors; DRE: digital rectal exam; mGs: modified Gleason score; PCPT: Prostate Cancer Prevention Trial;
PSA: prostate-specific antigen; REDUCE: Reduction by dutasteride of prostate cancer.
1. Thompson et al. NEJM. 2003;349:215-24; 2. Andriole et al. NEJM. 2010;362:1192-202; 3. Hamilton et al. BMC Med. 2011;9:105.
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COMBINATION THERAPY
• Combined alpha-blocker and 5-ARI therapy is effective for LUTS
associated with prostatic enlargement
• Improves symptom score and peak urinary flow greater than either
monotherapy option
• Delays symptomatic disease progression
• Decreased risk of urinary retention and/or prostate surgery
5-ARI: 5-alpha reductase inhibitor.
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS; 2. Nickel et al. CUAJ. 2010;4:310-6.
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54. NEW THERAPEUTIC OPTION:
PDE5 INHIBITOR
54
54
• PDE5 inhibitors* promote
smooth muscle relaxation to:1
• Improve LUTS
• Improve quality of life
• Effective in men with or
without ED2
GMP
Smooth
muscle
relaxation
cGMP
Smooth
muscle
contraction
Click here for
data on PDE5i’s
*Tadalafil is the only PDE5 inhibitor approved for BPH-LUTS (approved in Canada June 2012).
cGMP: cyclic guanosine monophosphate; GMP: guanosine monophosphate; PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor.
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS;
BPH-LUTS HOME
2. Broderick et al. Urology. 2010;75:1452-8.

55. WHEN SHOULD PDE5 INHIBITORS
BE CONSIDERED?
55
55
Where would you place
PDE5 inhibitors in your
BPH-LUTS armamentarium?
PDE5: phosphodiesterase 5.
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56. PHYTOTHERAPEUTIC AGENTS
FOR BPH-LUTS
56
56
• Phytotherapies for BPH-LUTS:1
• Serenoa repens (saw palmetto berry extract)
• Pygeum africanum (African plum)
Do you recommend
phytotherapy to your patients
for BPH-LUTS treatment?
1. Nickel et al. CUAJ. 2010;4:310-6.
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57. NO SIGNIFICANT IMPROVEMENT OF
BPH-LUTS WITH SAW PALMETTO
57
57
CUA guidelines do not recommend phytotherapy
for standard care of BPH-LUTS1
• Treatment with saw palmetto resulted in no significant
improvement in symptoms or objective measures of BPH2
Click here for
data on Saw Palmetto
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Bent et al. NEJM. 2006; 354:557-66.
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BPH-LUTS MEDICATIONS SIDE EFFECTS
Q
What are the most common side effects
with BPH-LUTS medications?
Alpha-blockers:1
5α-reductase inhibitors:1
• Retrograde ejaculation
• Reduced libido
• Erectile dysfunction
• Erectile dysfunction
Click on drug class
• Asthenia
• Decreased ejaculate
for complete
listing
• Dizziness
volume
of side effects
• Orthostatic hypotension
• Breast tenderness
• Nasal congestion
PDE5 inhibitors:2
• Headache
How do you educate patients
• Facial flushing
to manage side effects?
• Dyspepsia
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS;
2. Cialis Product Monograph. Eli Lilly Canada Inc.
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CASE SCENARIOS
Which therapy would you prescribe to a patient
with moderate-severe BPH-LUTS?
Q
Case Description
Recommendation
Moderate-severe bother (PSA 1.3 ng/mL)
α-blocker
What if he also had...
Diabetes?
α-blocker
Hypertension?
α-blocker
ED?
α-blocker or PDE5i
Signs of prostatic enlargement (PSA >1.5 ng/mL)?
5-ARI
Signs of prostatic enlargement (PSA >1.5 ng/mL) and ED?
5-ARI and/or PDE5i
Bothersome sexual side effects with α-blocker or 5-ARI?
PDE5i
5-ARI: 5-alpha reductase inhibitor; PDE5i: phosphodiesterase 5 inhibitor; PSA: prostate-specific antigen.
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60. TAKE HOME MESSAGES:
TREATMENT OPTIONS FOR PATIENTS WITH LUTS
60
60
• Alpha-blockers are a first-line option for men with symptomatic bother who
desire treatment
• 5ARI’s are an effective option for symptomatic patients with demonstrable
prostatic enlargement
• Combination alpha-blocker and 5-ARI therapy improves symptom score and peak
urinary flow vs. monotherapy; appropriate for patients with LUTS associated with
prostatic enlargement
• A PDE5 inhibitor can be used once-daily in men with moderate to severe
symptoms and bother, to effectively reduce symptoms of BPH-LUTS while
maintaining sexual function
• Phytotherapy is not recommended by the CUA
5-ARI: 5-alpha reductase inhibitor; PDE5: phosphodiesterase 5.
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BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS
4
When should I refer a
patient to a urologist?
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LEARNING OBJECTIVES
• After completing this question participants will be able to:
• Recognize when referral to a specialist is appropriate for an efficient sharedcare approach
• Assess indications for surgery and be aware of surgical options for patients
with BPH-LUTS
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63. WHEN SHOULD I REFER A
PATIENT TO A UROLOGIST?
63
63
Considerations:
• To rule out prostate cancer (abnormal
PSA level and/or abnormal DRE)
• Hematuria
• Unresponsive to therapy
• Patient preference
• Surgical management
DRE: direct rectal exam; PSA: prostate-specific antigen.
1. Nickel JC. Can Urol Assoc J. 2010;4:127-8.
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WHAT IS CONSIDERED
AN ABNORMAL PSA VALUE?
• Rapid change in PSA over 1 year1
• 0.75 ng/mL/year when PSA is 4-10 ng/mL
• High PSA value for age1,2
• 4.0 ng/mL was originally used to differentiate normal PSA level from pathologic
elevation
• Age-specific references have been used to improve sensitivity
Age Group
Parameter3
40-49
50-59
60-69
70-79
Serum PSA
Concentration (ng/mL)
0-2.5
0-3.5
0-4.5
0-6.5
PSA: prostate-specific antigen.
1. Izawa et al. 2011. Can Urol Assoc J. 2011;5:235-40; 2. Oesterling et al. JAMA. 1993;270:860-4; 3. Moul et al. J Urol 2007;177:499-503.
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BPH-LUTS ON THE RISE
• Approximately 40% of Canadian men >50 years of age are thought
to have moderate-severe LUTS1
• Require an approach involving both the primary care practitioner
and a urologist for efficient management1,2
• Urologist confirms the diagnosis, rules out prostate cancer, initiates therapy (either
watchful waiting, medical or surgical); transfers patient back to primary care
practitioner
• Primary care practitioner follows LUTS; monitors for progression or complications,
monitor PSA (and DRE) if indicated; refer back to urologist, as necessary
DRE: direct rectal exam; PSA: prostate-specific antigen.
1. Rawson NS and Saad F. Can Urol Assoc J. 2010;4:123-7; 2. Nickel. Can Urol Assoc J. 2010;4:127-8.
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PROSTATE OBSTRUCTION
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PATIENT SELECTION
Q
•
•
•
•
•
When is surgery indicated
for BPH-LUTS?
Renal insufficiency
LUTS complications
Patient requests surgical treatment
Medication is ineffective
Medication side effects are intolerable
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Novara et al. European Urology Supplements. 2006;5:418-29.
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SURGICAL OPTIONS
Q
What are the surgical options for BPH-LUTS?
Prostate Size
Very Large
(Volume ≥ 80-100 g)1
Open prostatectomy
Laser prostatectomy
• Holmium
• Green light
Large
(Volume 30-80 g)1
TURP
Laser prostatectomy
• Holmium
• Green light
Smaller
(Volume <30 g)1
TURP
Minimally Invasive
• TUMT*
• TUNA*
*Not insured in Canada.
TUMT: transurethral microwave therapy; TUNA: transurethral needle ablation; TURP: transurethral resection of the prostate.
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.
Click on the
underlined
“procedures”
for more
specific
information
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RISKS OF SURGERY
• Excessive bleeding requiring blood transfusion
• TUR syndrome
• Permanent sexual side effects:
• Retrograde ejaculation
• Erectile dysfunction (less common)
• Urinary tract infections
• Urinary incontinence
• Need for retreatment:
• Prostate regrowth
• Bladder/urethral strictures
TUR: transurethral resection.
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.
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TAKE HOME MESSAGES:
REFERRAL AND SURGERY
• Consider referral to a specialist:
•
•
•
•
•
To rule out prostate cancer (abnormal PSA/DRE)
If presence of hematuria
If patient is unresponsive to therapy
For surgical management
If patient indicates a preference for referral
• Surgery should be considered in patients with LUTS complications
or where medication is ineffective/intolerable
• Patients can be managed in a shared-care approach
• Majority of patients with BPH-LUTS will never require a urologist
DRE: direct rectal exam; PSA: prostate-specific antigen.
1. Nickel JC. Can Urol Assoc J. 2010;4:127-8.
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71
BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS
5
How should I follow-up with
a BPH-LUTS patient?
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72
LEARNING OBJECTIVES
• After completing this question participants will be able to:
• Assess time-to-symptom improvement for each pharmacological option and
establish a follow-up strategy
• Evaluate options for non-responders
BPH-LUTS HOME

73. HOW SHOULD I FOLLOW-UP WITH
A BPH-LUTS PATIENT?
73
73
• Symptom assessment 4-12 weeks
following diagnosis
• Subsequent follow-up should occur at
6 months and then annually
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS.
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74
ASSESS TREATMENT RESPONSE
• The time required to observe improvement of symptoms varies
depending upon the class of medication
Drug Class
Time for Symptom Improvement
α-blockers
•
•
2-4 weeks to develop fully
Hours to days for statistically significant
difference over placebo*1,2
5α-reductase inhibitors
•
At least 6 months1,3
•
4 weeks to reach statistically significant
symptom improvement4
PDE5 inhibitors
*Silodosin shows statistically significant symptom improvement after 3-4 days.
PDE5: phosphodiesterase 5.
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS; 2. Rapaflo Product Monograph. Watson Laboratory Inc;
3. Proscar Product Monograph. Merck Canada Inc; 4. Porst et al. Eur Urol. 2011;60:1105-13.
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NON-RESPONSE TO TREATMENT
Q
What should be done if
symptoms have not improved?
Consider:
• Optimizing current treatment regimen:
• Increase dose
• Switch agent
• Add agent
• Re-evaluate diagnosis (consider OAB)
• Refer to urologist
OAB: overactive bladder.
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TAKE HOME MESSAGES
• Follow-up 4-12 weeks following diagnosis
• Follow-up should include symptom assessment
• Optimize treatment regimen or re-evaluate diagnosis if symptoms
have not improved:
•
•
•
Increase dose
Switch agent
Add agent
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-neurogenic LUTS.
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BENIGN PROSTATIC HYPERPLASIALOWER URINARY TRACT SYMPTOMS
Supplementary Slides
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SYMPTOM SEVERITY MEASURE
• International Prostate Symptom Score (IPSS)
• Assessed based on reported frequency of 7 symptoms and impact on quality of life
• Patients rate questions on a scale of 0-5
• 0 = not at all
• 5 = almost always
• Sum of answers determines the severity of symptoms
Mild: 1-7
Moderate: 8-19
Severe: 20-35
Next
1. Barry et al. J Urol. 1992;148:1549-57.
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IPSS ASSESSMENT
Symptom
Question
1. Incomplete emptying:
How often have you had the sensation of not emptying your bladder?
2. Frequency:
How often have you had to urinate less than every 2 hours?
3. Intermittency:
How often have you found you stopped and started again several times
when you urinate?
4. Urgency:
How often have you found it difficult to postpone urination?
5. Weak stream:
How often have you had a weak urinary stream?
6. Straining:
How often have you had to strain to start urinating?
7. Nocturia:
How many times did you typically get up at night to urinate?
8. Quality of life:*
If you were to spend the rest of your life with your urinary condition as
is, how would you feel about it?
Return to
Slide 18
*Rated on a scale of 0-6, with 0 being delighted and 6 being terrible.
IPSS: International Prostate Symptom Score.
1. Barry et al. J Urol. 1992;148:1549-57.
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SEXUAL HEALTH INVENTORY FOR MEN
• Used to assess the severity of ED in sexually active men
• Shortened validated version of the IIEF
Over the Past 6 months:
1.
How do you rate your confidence that you could get and keep an erection?
2.
When you had erections with sexual stimulation, how often were your erections
hard enough for penetration?
3.
During sexual intercourse, how often were you able to maintain your erection after
you had penetrated (entered) your partner?
4.
During sexual intercourse, how difficult was it to maintain your erection to
completion of intercourse?
5.
When you attempted sexual intercourse, how often was it satisfactory to you?
Return to
Slide 23
IIEF: International Index of Erectile Function.
1. Rosen et al. Int J Imp Res. 1999;11:319-26.
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MILD SYMPTOMS
LUTS Presentation
Mild Symptoms
Small Prostate
Large Prostate
Watchful Waiting
Watchful Waiting
or
5-ARI
Return to
Slide 48
5-ARI: 5-alpha reductase inhibitor.
1. Nickel et al. CUAJ. 2010;4:310-6.
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82. MODERATE-SEVERE SYMPTOMS:
NO BOTHER
82
82
LUTS Presentation
Moderate – Severe Symptoms
No Significant Bother
Small Prostate
Watchful Waiting
Large Prostate
Watchful Waiting
or
5-ARI
Return to
Slide 48
5-ARI: 5-alpha reductase inhibitor.
1. Nickel et al. CUAJ. 2010;4:310-6.
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83. MODERATE-SEVERE SYMPTOMS:
MODERATE-SEVERE BOTHER
83
83
LUTS Presentation
Moderate – Severe Symptoms
Moderate – Severe Bother
Small Prostate
Large Prostate
Alpha-Blocker
or
Surgical Options
Alpha-Blocker
or
5-ARI
or
Combination Therapy
or
Surgical Options
Return to
Slide 48
5-ARI: 5-alpha reductase inhibitor.
1. Nickel et al. CUAJ. 2010;4:310-6.
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ALL PDE5 INHIBITORS HAVE BEEN
SHOWN TO IMPROVE BPH-LUTS
Sildenafil1*
0
Vardenafil2*
Weeks
6
12
0
-1
8
0
-1
Mean Change
in Symptom Score
Mean Change
in Symptom Score
0
Weeks
4
-2
-3
-4
-5
-6
Placebo
Sildenafil
-7
Tadalafil3
0
Mean Change
in Symptom Score
0
-2
Weeks
6
-2
-3
-4
-5
Vardenafil
Placebo
-6
-7
12
Placebo
Tadalafil 5 mg
Tadalafil 20 mg
-4
-6
-8
Next
-10
*Not indicated for the treatment of BPH-LUTS. PDE5: phosphodiesterase 5.
1. McVary et al. J Urol. 2007;177:1071-7; 2. Stief et al. Eur Urol. 2008;53:1236-44.; 3. McVary et al. J Urol. 2007;177:1401-7.
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PDE5 INHIBITORS FOR BPH-LUTS
Study
Description
Length
Effect on LUTS
McVary et al,
2007
• 369 men with LUTS and ED
• Daily sildenafil* vs. placebo
12 weeks
• Significant ↓ IPSS
• Significant ↑ QoL
• ↔ Qmax and Qav
Tuncel et al,
2010
• 60 men with BPH-LUTS
• Sildenafil* (4 days/week) or
tamsulosin or combination
8 weeks
• Improved urinary symptoms with
tamsulosin/combination
• ↑ erectile function with sildenafil/combination
McVary et al,
2007
• 281 men with BPH-LUTS
• Tadalafil once daily
12 weeks
• Significant ↓ IPSS at 6 and 12 weeks
• ↔ Qmax and Qav
Roehrborn et al,
2008
• 886 men with BPH-LUTS
• Daily tadalafil
12 weeks
• Significant improvement in urinary symptoms
Stief et al,
2008
• 222 men with BPH-LUTS
• Vardenafil* twice daily
8 weeks
• Significant improvement in irritative/obstructive
symptoms and general QoL
Gacci et al,
2011
• 60 men with persistent
irritative urinary symptoms
• Vardenafil* + tamsulosin vs.
tamsulosin
12 weeks
• Significant reduction of irritative symptoms with
combined therapy
No change in urinary flow rate with PDE5 inhibitors
Next
*Not indicated for the treatment of BPH-LUTS.
IPSS: International Prostate Symptom Score; Qav: average flow rate; Qmax: maximum flow rate; QoL: quality of life; PDE5: phosphodiesterase 5.
1. Gacci et al. Eur Urol. 2011;60:809-25.
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86. REASONS FOR LACK OF LUTS
IMPROVEMENT WITH PDE5I FOR ED
86
In the past, why have patients not
reported improvements in LUTS when they have
used a PDE5 inhibitor for ED?
Q
• Treatment of BPH-LUTS with PDE5 inhibitors requires daily dosing
•
Many patients use PDE5 inhibitors on-demand for ED
• Short-acting PDE5 inhibitors (sildenafil/vardenafil) require TID dosing to
reach appropriate plasma levels
• Only long-acting PDE5 inhibitors are clinically relevant for BPH-LUTS
Next
PDE5: phosphodiesterase 5; PDE5i: phosphodiesterase 5 inhibitor; TID: three-times daily.
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TADALAFIL 5 MG BUT NOT 2.5 MG IS
EFFECTIVE FOR THE TREATMENT OF BPH-LUTS
Mean Change in Total IPSS Score
from Baseline to Endpoint
PLA Run In
Week - 4
Baseline
Week 0
Placebo
Week 4
Week 8
Week 12
0
TAD 2.5 mg
TAD 5.0 mg
-1
TAD 10.0 mg
-2
TAD 20.0 mg
-3
Clinically meaningful
improvement
-4
-5
-6
-7
-8
-9
Tadalafil 2.5 mg p<0.05 at week 4
Tadalafil 5, 10, and 20 mg p<0.01 for weeks 4, 8, and 12
compared to placebo
Next
IPSS: International Prostate Symptom Score; PLA: placebo; TAD: tadalafil.
1. Roehrborn et al. J Urol. 2008;180:1228-34.
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EFFICACY OF PDE5I’S FOR BPH-LUTS
LS Mean Change from Baseline
in IPSS Total Score
0
Placebo
Tadalafil
Tamsulosin
-1
-2
-3
-4
-5
-6
-7
0
2
4
6
8
Duration of Treatment (weeks)
10
12
Return to
Slide 52
IPSS: International Prostate Symptom Score; LS: least squares; PDE5I: phosphodiesterase 5 inhibitor.
1. Oelke et al. Eur Urol. 2012;61:917-25.
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SAW PALMETTO DOES NOT
IMPROVE BPH-LUTS
Changes in Primary and Secondary Outcome Measures
Measure
Saw Palmetto
(n=112)
Placebo
(n=113)
Difference between
Groups (95% CI)
mean (±SE) change
Primary outcomes
AUASI score
-0.68±0.35
-0.72±0.35
0.04 (-0.93 to 1.01)
Peak urinary flow rate (ml/sec)
0.42±0.34
-0.01±0.34
0.43 (-0.52 to 1.38)
• No significant differences were observed in symptom improvement
between saw palmetto and placebo
Return to
Slide 55
AUASI: American Urological Association Symptom Index; CI: confidence interval.
1. Bent et al. NEJM. 2006;354:557-66.
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ALPHA-BLOCKER SIDE EFFECTS
α-Blocker
Side-effect Profile
Alfuzosin1
Dizziness and headache, low incidence of postural symptoms, potential for syncope,
priaprism and atrial fibrillation
Doxazosin2
Dizziness/light-headedness, hypotension/syncope, drowsiness, fatigue (tiredness),
swelling of the feet, shortness of breath, painful erection, ejaculation disorders (e.g.
retrograde ejaculation)
Tamsulosin3
Dizziness, headache, palpitations, hypotension, rhinitis, diarrhea, nausea and vomiting,
constipation, asthenia, itching and hives (urticaria), abnormal/retrograde ejaculation,
fainting, priaprism
Terazosin4
Dizziness/faintness (as a result of blood pressure drop), back pain, constipation,
diarrhea, drowsiness or sleepiness, dry mouth, flatulence, headache, impotence,
indigestion, decreased libido, nasal congestion, nausea, urinary frequency, weakness or
weight gain
Silodosin5
Retrograde ejaculation, dizziness, diarrhea, light-headedness upon standing or sitting up
abruptly, headache, nasopharyngitis and nasal congestion
Return to
5-ARIs
Slide 56
5-ARIs: 5-alpha reductase inhibitors.
1. Xatral Product Monograph. Sanofi-Aventis Canada Inc; 2. Cardura Product Monograph. Pfizer Canada Inc;
3. Flomax Product Monograph. Boehringer Ingelheim (Canada) Ltd; 4. Hytrin Product Monograph. Abbott Laboratories;
5. Rapaflo Product Monograph. Watson Laboratories Inc.
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91
5-ARI SIDE EFFECTS
5-ARI
Side-effect Profile
•
•
•
Finasteride1
•
•
•
•
Dutasteride2
•
•
•
•
•
•
•
Impotence/inability to have an erection that continues after stopping the
medication
Decreased libido
Problems with ejaculation, such as a decrease in the amount of semen released
during sex
Male infertility and/or poor quality of semen
Breast tenderness or swelling
Testicular pain
Depression
Impotence
Decreased libido
Breast disorders (including breast enlargement and tenderness)
Ejaculation disorders
Dizziness
Hair loss
Abnormal hair growth
PDE5i’s
Return to
Slide 56
5-ARI: 5-alpha reductase inhibitor; PDE5i: phosphodiesterase 5 inhibitor.
1. Proscar Product Monograph. Merck Canada Inc; 2. Avodart Product Monograph. GlaxoSmithKline Inc.
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PDE5 INHIBITOR SIDE EFFECTS
PDE5i
Side-effect Profile
Sildenafil1
•
•
•
•
•
Headache
Facial flushing
Dyspepsia
Nasal congestion
Abnormal vision colour tinge
Tadalafil2
•
•
•
•
•
Headache
Dyspepsia
Back pain
Myalgia
Nasal congestion
Vardenafil3
•
•
•
•
•
Headache
Flushing
Rhinitis
Dyspepsia
Sinusitis
Return to
Slide 56
PDE5i: phosphodiesterase 5 inhibitor.
1. Viagra Product Monograph. Pfizer Canada Inc; 2. Cialis Product Monograph. Eli Lilly Canada Inc; 3. Staxyn Product Monograph. Bayer Inc.
BPH-LUTS HOME

93. 93
93
TRANSURETHRAL RESECTION
OF THE PROSTATE
Uses electric current to remove tissue
from the transition zone of the prostate
• Electric current can be monopolar or bipolar
•
Similar safety and efficacy profiles1
•
Bipolar TURP thought to be advantageous2
•
Use of isotonic irrigating fluid eliminates need for grounding pads and risk of
TUR syndrome
Next
TUR: transurethral resection; TURP: transurethral resection of the prostate.
1. Méndez-Probst et al. CUAJ. 2011;5:385-9; 2. Hueber et al. Can Urol Assoc J. 2011;5:390-1.
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DISADVANTAGES OF TURP
Disadvantages:1,2,3
• Risk of blood transfusion
• TUR syndrome
• Need for retreatment (14.7% in 8 year follow-up)
• Retrograde ejaculation
• Risk of impotency
• Contraindicated in patients on anticoagulants
Return to
Slide 66
TUR: transurethral resection. TURP: transurethral resection of the prostate.
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS;
3. Yang et al. J Urol. 2001;165:1526-32.
BPH-LUTS HOME

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LASER PROSTATECTOMY
Uses laser energy to remove obstructing tissue from the
prostate through tissue coagulation or
vaporization/ablation1
1. Holmium laser:1
•
•
•
Operational wavelength 2140 nm in pulsed mode
Performed at 60-80 W
HoLRP on glands <60 g, HoLEP on glands >60 g
2. Green light laser (PVP):2
•
•
Wavelength of 532 nm
Available in 80-W, 120-W and 180-W models3
Return to
Slide 66
HoLRP: holmium laser resection; HoLEP: holmium laser enucleation; PVP: photoselective vaporization prostatectomy.
1. Tooher et al. J Urol. 2004;171:1773-81; 2. Hai. Urology. 2009;73:807-10.
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HOLMIUM LASER
• 10 year follow-up study has found HoLEP to be equivalent to TURP
• Reduced requirement for re-operation1
• May safely be considered a new, size independent, gold standard for symptomatic
BPH1
• In prostates >100 g, HoLEP was as effective as open prostatectomy
in reducing micturition and the need for re-operation2
• Suitable for patients on
anticoagulants3
Disadvantages:4
• Retrograde ejaculation (75-80%)
• Dysuria is common
• Longer operation time than TURP
HoLEP: holmium laser enucleation; TURP: transurethral resection of the prostate.
1. Elmansy et al. J Urol. 2011;186:1972-6; 2. Kuntz et al. Eur Urol. 2008;53:160-6; 3. Elzayat et al. J Urol. 2006;175:1428-32;
4. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.
Return to
Slide 66
BPH-LUTS HOME

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GREEN LIGHT LASER
• Ideal for large prostates (30-80 g)
• Improvement in symptoms and re-operation rate comparable to
TURP1
• Safe and effective in patients on anticoagulants2
Disadvantages:3
• Limited long-term data, particularly with
120-W and 180-W
• Longer operation time than TURP
• Dysuria is common
TURP: transurethral resection of the prostate.
1. Ruszat et al. Eur Urol. 2008;54:893-901; 2. Ruszat et al. Eur Urol. 2007;1031-41;
3. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.
Return to
Slide 66
BPH-LUTS HOME

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OPEN PROSTATECTOMY
Obstructive prostatic adenomas are
surgically removed through incisions from the inside of the
bladder or through the anterior prostatic capsule1
• Oldest surgical treatment for BPH
• Considered when prostate is too large (80-100 g) for TURP
for fear of:2
• Incomplete resection
• Significant bleeding
• Risk of TUR syndrome (dilutional hyponatremia)
Next
TUR: transurethral resection; TURP: transurethral resection of the prostate.
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS;
2. Nickel et al. CUAJ. 2010;4:310-6.
BPH-LUTS HOME

99. DISADVANTAGES OF OPEN
PROSTATECTOMY
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•
99
99
Most invasive of the surgical procedures
Risk of bladder stone development
Risk of bladder diverticula
Risk of incontinence
Risk of bladder neck contracture and urethral stricture
Return to
Slide 66
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.
BPH-LUTS HOME

100. TRANSURETHRAL INCISION
OF THE PROSTATE
10
100
0
Incisions are made in the bladder outlet to improve symptoms
• No tissue is removed1
• Ideal for prostate volumes <30 g
Advantages over TURP1
Disadvantages1
•
•
•
•
•
•
•
•
•
Reduced bleeding incidents
Shorter operation time
Avoidance of TUR syndrome
Minimal and shorter post-operative
bladder irrigation
Low risk of retrograde ejaculation
Shorter times for catheterization
Shorter hospitalization
Higher rate of symptom recurrence
Need for additional surgery
Return to
Slide 66
TUR: transurethral resection; TURP: transurethral resection of the prostate.
1. Oelke et al. 2011 European Urology Association. Treatment Guidelines for Non-Neurogenic LUTS.
BPH-LUTS HOME

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101
1
MINIMALLY INVASIVE: TUMT
Transurethral microwave therapy (TUMT)1
Microwave heating destroys excess prostate tissue2
• Considered in patients with:
• Moderate symptoms
• Small to moderate sized prostate gland
• Desire to avoid more invasive therapy
• Associated with a higher 5 year re-treatment rate than TURP
Return to
Slide 66
TURP: transurethral resection of the prostate.
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Illing. Eur Urol Suppl. 2007;6:701-9.
BPH-LUTS HOME

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2
MINIMALLY INVASIVE: TUNA
Transurethral needle ablation (TUNA)1
Generates necrosis by heat application using two needles2
• Considered for younger, active individuals where sexual function is
an important quality of life issue
• Limited data on long term outcomes
• Higher re-treatment rate than TURP2
Return to
Slide 66
TURP: transurethral resection of the prostate.
1. Nickel et al. CUAJ. 2010;4:310-6; 2. Illing. Eur Urol Suppl. 2007;6:701-9.
BPH-LUTS HOME