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CURRICULUM VITAE

Name : Paksi Satyagraha, MD., MSc., Urologist


Home Address : Jl. Terusan Danau Kerinci IA No 18, Sawojajar,
Malang, East Java. Indonesia.65154.
Office : Urology Department SaifulAnwar General Hospital Malang.
Jl. Jaksa Agung Suprapto No.2, Malang, East Java.
Indonesia – 65111
Mobile : +62 81335094897
Home phone : +62 341 302148
E-mail : paksisatyagraha@yahoo.com
paksisatyagraha@gmail.com
uropas.fk@ub.ac.id

Curret Position : Medical Staff in Urology Department


Genitourinary Reconstruction Division
Saiful Anwar General Hospital, Malang, East Java Indonesia
Dr. Paksi Satyagraha, MKes, SpU(K)
Urology Department, Faculty of Medicine-University of
Brawijaya, Saiful Anwar General Hospital, Malang, East
Java, Indonesia

paksisatyagraha@gmail.com
@paksi_PAS
uropas.fk@ub.ac.id
Definitions of terms used in the context of BPH1-3

• LUTS – lower urinary tract symptoms that can be divided into


storage, voiding and post micturition symptoms

• BPH – benign prostatic hyperplasia is reserved for the histological


pattern it describes

• BPE – benign prostatic enlargement is used when there is a gland


enlargement

• BPO – benign prostatic obstruction is used when obstruction has


been proven by pressure flow studies, or is highly suspected from
flow rates and if the gland is enlarged

1. Abrams P et al. J Urol 2013;189: S93-S101; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/education/clinical-
guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology
Guidelines 2016; accessed on 28-04-16 through http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#3
For Healthcare Professional Use only
What do we call BPH?

Bladder

Central and
Prostate peripheral zones

Transition zone

Urethra

Normal prostate Enlarged prostate

When mentioned in this presentation, “BPH” refers to


bothersome LUTS in men with BPE probably causing BPO
LUTS: Lower urinary tract symptoms; BPE: Benign prostatic enlargement; BPO: Benign prostatic obstruction

Abrams P et al. J Urol 2013;189: S93-S101; Wilson JD. Am J Med 1980;68:745–756

For Healthcare Professional Use only


Increasingly aging population
Men over 50 years old: population projections in Asia Pacific from 2001 to 2030
2015 Data (men over 50 years old)
Number of men over 50 years old

1,600,000 Hong Kong Hong Kong SAR, China 1,350,000


SAR, China
1,400,000 Singapore Singapore 909,000
1,200,000 Indonesia 22,482,000
1,000,000 Vietnam 8,537,000
Thailand 9,649,000
800,000
Philippines 7,298,000
600,000
Australia 3,825,000
400,000
2001 2006 2011 2016 2021 2026
Malaysia 2,792,000
years
Vietnam
14,000,000
Number of men over 50 years old

Thailand

Number of men over 50 years old


33,000,000 12,000,000
Philippine
Indon…
10,000,000 s
28,000,000
8,000,000
23,000,000
6,000,000
18,000,000
4,000,000

13,000,000 2,000,000
2001 2006 2011 2016 2021 2026 2001 2006 2011 2016 2021 2026

years years

Data from database: Health Nutrition and Population Statistics: Population estimates and projections. Last accessed April 2016;
http://databank.worldbank.org/data/reports.aspx?source=Health%20Nutrition%20and%20Population%20Statistics:%20Population%20estimates%20and
%20projections
The prevalence of BPH, BPE and LUTS
increases with age1-3
100 Sixth decade of life
BPH*3 70%
80
Prevalence %

60
BPE§1 50%
LUTS1 50%
40 (moderate to severe)

20 LUTS+BPE
34%
0
31‒40 41‒50 51‒60 61‒70 71‒80 81‒90
Data from different studies
Age (years)
*Prevalence of BPH in 1075 human prostate collected at autopsy; § Determined by digital rectal examination with a result of enlarged or not enlarged (n=448 )

Adapted from 1. Naslund MJ et al. Int J Clin Pract 2007;61:1437-45; 2. Verhamme KM et al. Eur Urol 2002;42:323-8; 3. Berry SJ et al. J Urol 1984;132:474-79.
STATISTIC IN SAIFUL ANWAR GENERAL HOSPITAL

NO DIAGNOSE TOTAL DIAGNOSE 2014 2015 2016 2017 TOTAL

1 Stone 1419 STONE 41 400 648 196 1285

2 BPH 1374 CARCINOMA 16 176 441 182 815

3 CA 860 BPH 18 84 218 118 448

4 Urethral Stricture 550 CHRONIC RENAL


2 81 156 73 312
FAILURE
5 Renal Colic 222
TBC UG 0 67 168 61 296
6 Hypospadia 110
DJ STENT 13 50 182 50 295
7 Flank Pain 83 ACUTE RENAL
1 26 100 46 173
8 FAILURE
UPJ Stenosis 45
SEPSIS 0 38 63 39 140
9 Neurogenic Bladder 23
Inpatients data from 2014 – May 2017
10 UDT 13

Outpatients data from October 2016 – May


2017

For Healthcare Professional Use only


Male LUTS have a multifactorial aetiology but
BPH is the most common reason1,2
Prospective, epidemiological, international
(France, Italy, Spain) study Cross-sectional US study
Men with LUTS ≥ 50 years (N=666)3 Men with LUTS >50 years (N=448)4

66% 48%
of men spontaneously of men reporting routinely
presenting to GP clinics to GP clinics have an
with LUTS have BPH enlarged prostate (DRE)

DRE: Digital rectal examination

1. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#3 2. Parsons JK. Curr Bladder Dysfunct Rep 2010;5:212–8; 3. Carballido J et al. Int J
Clin Pract 2011;65:989-96; 4. Naslund MJ et al. Int J Clin Pract 2007;61:1437-45.
BPH is a progressive condition and will get
worse if suboptimally treated1-3

• Over time, men with BPH may experience

 Worsening of symptoms and disease-specific quality of life


 Deterioration in peak urinary flow rate (Qmax)
 An increase in prostate volume

• BPH progression may lead to long-term complications

 Acute urinary retention (AUR)


 BPH-related surgery

1. Emberton M et al. Urology 2003;61:267-73; 2. Emberton M et al. Int J Clin Pract 2008:62:1076-86; 3. Fitzpatrick JM. BJU Int 2006;97(Suppl. 2):3-6.
For Healthcare Professional Use only
BPH significantly impacts daily living activities
Cross-sectional survey of 1610 men aged 40‒79 years in central Scotland

Percentage of men reporting that urinary symptoms interfered with


activities of daily living at least some of the time during the past month
60
BPH absent
50 BPH present

40
Patients (%)

34.7
32.4
29.9
30 27.1
21.0
20 18.4
15.1
13.2 13.4 12.8
10.3
10 8.0 6.7 6.2

0
Limits fluids Limits going to Limits fluids Not getting Cannot drive Limits going to Limits playing
before places without before travel enough sleep for two hours cinema, outdoor sports
bedtime toilets at night theatre,
church etc.

Adapted from Garraway WM et al. Br J Gen Pract 1993;43:318-21.


Most patients with BPH have existing co-morbidities

Patients (N=4979) presenting with LUTS in six European countries were evaluated for co-morbidities

Most commonly reported Incidence


comorbidities (%)
Hypertension 36.5
Coronary heart disease 12.5
Diabetes mellitus 10.3
Chronic respiratory failure 7.7
Chronic GI disease 7.4
Multiple co-morbidities 26.6

62% of patients presenting with LUTS have existing co-morbidities

Hutchison A et al. Eur Urol 2006;50:555-561.


Many men do not seek help despite having bothersome symptoms

Delay consultation for years


due to uncertainty, incomplete
knowledge, neglect1,2,3

Often seen as
Develop coping strategies
part of aging1,2,3
including self-medication
and structuring of daily
activities1
Men´s views
of LUTS

Embarrassment is a key reason men do not discuss LUTS with their physician 2,3

1. Gannon K et al. J Health Psychol 2004;9:411-420; 2. Carballido J et al. Int J Clin Pract 2009;63:1192-1197;
3. Kuritzky L. Rev Urol 2003;5(suppl 5):S42-S48.
Accurate assessment of male LUTS is crucial
because…

LUTS represent one of the most common clinical


complaints that increase with age in males

LUTS have multifactorial aetiology: many


conditions both urological and non-urological, may
contribute to male LUTS

Gratzke C et al. Eur Urol 2015;67:1099-109.

For Healthcare Professional Use only


Objectives of clinical assessment of
men with LUTS1,2
Establish
a differential diagnosis
Identify
men at risk of
progression
Define
Assess the clinical profile
patients’ values
Conservative
and preferences
treatment
Provide
Minimise the best evidence-based care Medical treatment
disease progression
and complications
Surgical treatment

1. Gratzke C et al. Eur Urol 2015;67:1099-109; 2. McVary T et al. AUA Guideline. Revised 2010. Available at:
http://www.auanet.org/common/pdf/education/clinical-guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016)
Initial assessment
1,2,3
on presentation with LUTS
Clinical assessment tests

Recommended by both EAU and AUA

Physical
Relevant medical Symptom score
Urinalysis examination
history questionnaires
including DRE

Recommended by EAU and AUA in selected patients


Frequency
Imaging of the
volume charts
Serum PSA upper urinary
and bladder
tract
diaries

Recommended by EAU and optional by AUA

Imaging of the Post-void


Uroflowmetry
prostate residual urine

PSA: Prostate specific antigen; EAU: European Association of Urology; AUA: American Urological Association
1. Gratzke C et al. Eur Urol 2015;67:1099-1109; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/education/clinical-
guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology
Guidelines 2016; accessed on 28-04-16 through http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#
Initial assessment
1,2,3
on presentation with LUTS
Clinical assessment tests

Recommended by both EAU and AUA

Physical
Relevant medical Symptom score
Urinalysis examination
history questionnaires
including DRE

Recommended by EAU and AUA in selected patients


Frequency
Imaging of the
volume charts
Serum PSA upper urinary Assessment tests
and bladder
tract
diaries most likely to be
feasible at GP office
Recommended by EAU and optional by AUA

Imaging of the Post-void


Uroflowmetry
prostate residual urine

1. Gratzke C et al. Eur Urol 2015;67:1099-1109; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/education/clinical-
guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology
Guidelines 2016; accessed on 28-04-16 through http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#
Initial assessment
1,2,3
on presentation with LUTS
Clinical assessment tests

Recommended by both EAU and AUA

Physical
Relevant medical Symptom score
Urinalysis examination
history questionnaires
including DRE

Recommended by EAU and AUA in selected patients


Frequency
Imaging of the
volume charts
Serum PSA upper urinary Assessment tests
and bladder
tract
diaries most likely to be
feasible at GP office
Recommended by EAU and optional by AUA

Imaging of the Post-void


Uroflowmetry
prostate residual urine

1. Gratzke C et al. Eur Urol 2015;67:1099-1109; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/education/clinical-
guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology
Guidelines 2016; accessed on 28-04-16 through http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#
Relevant medical history needed to assess the potential cause of LUTS

Medications that may


Differential diagnosis* Other risk factors*
cause or exacerbate LUTS*
• Bladder cancer • Anticholinergic agents • Cigarette smoking
• Bladder stones • Decongestants • Elevated blood
• Congestive heart failure • Diuretics pressure
• Diabetes mellitus • First-generation • Obesity
• Interstitial cystitis antihistamines • Regular alcohol
• Lumbosacral disc • Narcotics consumption
disease • Tricyclic antidepressants
• Multiple sclerosis
• Nocturnal polyuria
• Parkinson’s disease
• Primary bladder neck
hypertrophy
• Prostate cancer
• Prostatitis
• Radiation cystitis
• Urinary tract infection

*In alphabetical order.


Rosenberg MT 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;61:1535-46. Copyright 2007 The Authors.
Initial assessment
1,2,3
on presentation with LUTS
Clinical assessment tests

Recommended by both EAU and AUA

Physical
Relevant medical Symptom score
Urinalysis examination
history questionnaires
including DRE

Recommended by EAU and AUA in selected patients


Frequency
Imaging of the
volume charts
Serum PSA upper urinary Assessment tests
and bladder
tract
diaries most likely to be
feasible at GP office
Recommended by EAU and optional by AUA

Imaging of the Post-void


Uroflowmetry
prostate residual urine

1. Gratzke C et al. Eur Urol 2015;67:1099-1109; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/education/clinical-
guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology
Guidelines 2016; accessed on 28-04-16 through http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#
Urinalysis is used to determine other conditions1,2
A recommended primary evaluation in the presence of LUTS

Urinalysis (dipstick or microscopic/urinary sediment)

Urinalysis2 To determine other


conditions1,2

•Haematuria • For example


•Proteinuria • UTI
•Pyuria • Diabetes
•Glucosuria mellitus
•Ketonuria
•Positive nitrite test

UTI: Urinary tract infection


1. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#; 2. Gratzke C et al. Eur Urol 2015;67:1099-1109. Images reproduced with
permission from iStock
Initial assessment
1,2,3
on presentation with LUTS
Clinical assessment tests

Recommended by both EAU and AUA

Physical
Relevant medical Symptom score
Urinalysis examination
history questionnaires
including DRE

Recommended by EAU and AUA in selected patients


Frequency
Imaging of the
volume charts
Serum PSA upper urinary Assessment tests
and bladder
tract
diaries most likely to be
feasible at GP office
Recommended by EAU and optional by AUA

Imaging of the Post-void


Uroflowmetry
prostate residual urine

1. Gratzke C et al. Eur Urol 2015;67:1099-1109; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/education/clinical-
guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology
Guidelines 2016; accessed on 28-04-16 through http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#
Classification of LUTS

Symptom type Symptom

Storage symptoms Increased daytime frequency


(previously called irritative) Nocturia
Urgency
Urinary incontinence

Voiding symptoms Slow stream


(previously called obstructive) Splitting or spraying
Intermittent stream
Hesitancy
Straining
Terminal dribble

Post micturition symptoms Feeling of incomplete emptying


Post micturition dribble

Abrams P et al. Neurourol Urodyn 2002;21:167-78.

For Healthcare Professional Use only


International prostate symptom score (IPSS)
Assessment of severity and bother of LUTS in men (1/2)

• The IPSS has become the validated


international standard to assess LUTS
severity1
• It is an 8-item self-administered
questionnaire for patients2
• The first 7 items quantitatively measure the
level of symptoms, reported as a total IPSS
score
• Total IPSS score can range from 0–35;
three categories of symptom severity are
recognised based on this:
- Mild (0–7 points)
- Moderate (8–19 points)
- Severe (20–35 points)

 IPSS questionnaire may not be practical in the busy primary care setting3,4
 IPSS cannot be used as a diagnostic tool since other conditions can cause similar symptoms 3

1. Madersbacher S et al. Eur Urol 2004;46:547-554; 2. McVary T et al. AUA Guideline. Appendix 1A. Revised 2010. Available at:
http://www.auanet.org/common/pdf/education/clinical-guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Rosenberg MT et al.
Int J Clin Pract 2007;61:1535-46; 4. Carballido J et al. Int J Clin Pract 2011;65:989-96.
International prostate symptom score IPSS
Assessment of severity and bother of LUTS in men (2/2)

The last item of the IPSS questionnaire is a separate assessment of quality of life
based on a score range from 0-61,2

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?

1. Madersbacher S et al. Eur Urol 2004;46:547-554; 2. McVary T et al. AUA Guideline. Appendix 1A. Revised 2010. Available at:
http://www.auanet.org/common/pdf/education/clinical-guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016)
Initial assessment
1,2,3
on presentation with LUTS
Clinical assessment tests

Recommended by both EAU and AUA

Physical
Relevant medical Symptom score
Urinalysis examination
history questionnaires
including DRE

Recommended by EAU and AUA in selected patients


Frequency
Imaging of the
volume charts
Serum PSA upper urinary Assessment tests
and bladder
tract
diaries most likely to be
feasible at GP office
Recommended by EAU and optional by AUA

Imaging of the Post-void


Uroflowmetry
prostate residual urine

1. Gratzke C et al. Eur Urol 2015;67:1099-1109; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/education/clinical-
guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology
Guidelines 2016; accessed on 28-04-16 through http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#
Performing a digital rectal exam (DRE)
A recommended assessment in presence of LUTS to evaluate:

• Prostate size/volume
• Prostate shape
• Prostate consistency and
abnormalities suggestive of
prostate cancer
• Anal sphincter tone

Gratzke C et al. Eur Urol 2015;67:1099-1109. McVary T et al. AUA Guideline. Revised 2010. Available at:
http://www.auanet.org/common/pdf/education/clinical-guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016).
Furlan A et al. Int Braz J Urol 2008;34:572-76.
Initial assessment
1,2,3
on presentation with LUTS
Clinical assessment tests

Recommended by both EAU and AUA

Physical
Relevant medical Symptom score
Urinalysis examination
history questionnaires
including DRE

Recommended by EAU and AUA in selected patients


Frequency
Imaging of the
volume charts
Serum PSA upper urinary Assessment tests
and bladder
tract
diaries most likely to be
feasible at GP office
Recommended by EAU and optional by AUA

Imaging of the Post-void


Uroflowmetry
prostate residual urine

1. Gratzke C et al. Eur Urol 2015;67:1099-1109; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/education/clinical-
guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology
Guidelines 2016; accessed on 28-04-16 through http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#
Prostate serum antigen (PSA) testing1,2
• PSA is used in the diagnosis of prostate
cancer
• PSA levels vary with age
• Along with prostate size, serum PSA
provides prognostic information about:
– Prostate growth
– Symptoms and bother deterioration
– Flow rate worsening
– Risk for AUR and surgery

PSA testing is recommended in presence of LUTS only if a diagnosis of


prostate cancer will change the management or if PSA can assist in
decision-making in patients at risk of progression of BPH1

1. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/
education/clinical-guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); Image reproduced with permission from iStock
PSA and total prostate volume have a
strong age-dependent relationship
The close correlation between prostate volume and PSA enables
PSA to be used as a surrogate to estimate prostate volume

70 75
70
65
65
60
60
55 55
50
50
45
45 40

40 Age
(years)
35
30
1 2 3 4 5 6 7 8
Serum PSA (ng/mL)
Reprinted from Urology, vol 53, Roehrborn CG, et al, Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia, pp 581-9, Copyright 1999 with permission from Elsevier.

.
Initial assessment
1,2,3
on presentation with LUTS
Clinical assessment tests

Recommended by both EAU and AUA

Physical
Relevant medical Symptom score
Urinalysis examination
history questionnaires
including DRE

Recommended by EAU and AUA in selected patients


Frequency
Imaging of the
volume charts
Serum PSA upper urinary Assessment tests
and bladder
tract
diaries most likely to be
feasible at GP office
Recommended by EAU and optional by AUA

Imaging of the Post-void


Uroflowmetry
prostate residual urine

1. Gratzke C et al. Eur Urol 2015;67:1099-1109; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/education/clinical-
guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology
Guidelines 2016; accessed on 28-04-16 through http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#
Frequency volume chart (FVC) and bladder diary
Assessment of LUTS with a prominent storage component or nocturia

Total voided volume


FVC • Nocturnal polyuria index
Bladder diary • Volume of individual
Volume and time voids (mean and range)
of each void Additional information
Fluid intake
Use of pads
Activities
Symptom scores

Voiding diary
Time Intake Urge Voided Leak Activity

FVCs should be Type Amount


performed for the
duration of at least 8 am coffee 1 cup

9.10 x x
3 days
10.15 water 1 cup

10.30 x standing

Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#
GPs can use assessment data to build BPH
patient risk profile1
Risk factors for disease progression include:

• Advancing age (>60 years)2

• Moderate to severe LUTS (IPSS ≥8)3

• Increased prostate volume (≥ 30mL)2

• Elevated PSA level (≥1.5 ng/mL)2

1. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#; 2. Emberton M et al. Int J Clin Pract 2008; 62:1076-86; 3. Tanguay S et al. Can Urol
Assoc J 2009;3(Suppl2):S92-100.
When to refer to the urologist?
Based on patient assessment1-3

Complicated LUTS
• History of recurrent urinary tract Suspicion of prostate cancer
infections or other infection
• Microscopic or gross hematuria • Elevated PSA Other
• Prior genitourinary surgery • Abnormal prostate
exam (nodules) • Elevated prostate
• Suspicion of neurologic cause symptoms
of symptoms • Uncertain diagnosis
• Findings or suspicion of urinary • Unsuccessful initial
retention medical management
• Meatal stenosis
• History of genitourinary trauma
• Pelvic pain

1. Rosenberg MT et al. Int J Clin Pract 2007;61:1535-46; 2. Kuritzky L. Rev Urol 2003;5(Suppl 5):S42-8; 3. Kapoor A. Can J Urol 2012;19(Suppl 1):10-7.
Objectives of clinical assessment of
men with LUTS1,2,3
Establish
a differential diagnosis
Identify
men at risk of
progression
Define
Assess the clinical profile
patients’ values
Conservative
and preferences
treatment
Provide
Minimise the best evidence-based care Medical treatment
disease progression
and complications
Surgical treatment

1. Gratzke C et al. Eur Urol 2015;67:1099-109; 2. McVary T et al. AUA Guideline. Revised 2010. Available at: http://www.auanet.org/common/pdf/education/clinical-
guidance/Benign-Prostatic-Hyperplasia.pdf (Accessed: May 2016); 3. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology
Guidelines 2016; accessed on 28-04-16 through http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#;
Treatment options of LUTS

Conservative • Watchful waiting


treatment • Behavioural and dietary modifications

• Alpha-blockers (AB)
Medical treatment • 5-alpha reductase inhibitors (5-ARI)
• Phosphodiesterase-5 (PDE-5) inhibitors
• Muscarinic receptor antagonists
• Beta-3 agonist
• Combination therapy
- AB + 5-ARI
- AB + muscarinic receptor antagonist

• Transurethral resection/incision of the prostate


• Open prostatectomy
Surgical treatment • Transurethral microwave therapy
• Transurethral needle ablation of the prostate
• Lasers
Not all treatment options may be available in all countries • Stents
Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#;
Medical Treatment of BPH

Alpha blocker 5-ARI


• Rapid improvement • Late improvement
• Can not prevent progression • Can prevent progression

Antimuscarinic Betha-3 Agonist


• Superior for storage LUTS • Superior for storage LUTS
• Affect parasympathetic • Doesnt affect parasympathetic

PDE-5i
• Indicated for BPH with ED

Nunes et al. Rev Assoc Med Bras 2017; 63(2):95-99

For Healthcare Professional Use only


Recommendations for other BPH treatments

Conservative medical treatment


Self-management programmes combined with standard care (watchful waiting
followed by medical treatment and surgery) shown to significantly improve patient
outcomes compared with standard care alone

Phosphodiesterase-5 (PDE-5) inhibitors


May be used in men with moderate-to-severe LUTS with or without erectile
dysfunction

Muscarinic receptor antagonists


May be used in men with moderate-to-severe LUTS who mainly have bladder
storage symptoms

Alpha-blockers + muscarinic receptor antagonist combination therapy


In patients with moderate-to-severe LUTS if relief of storage symptoms has been
insufficient with monotherapy with either drug

Limited evidence to support their use in patients at increased risk of progression

Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#.
SMOOTH
BPH MUSCLE
TONUS:
Dynamic
PROSTATIC
Static Dynamic MASS:
component component Static

Voiding
problems
Alpha
adrenergik
receptor
Bladder
Storage distribution in
aging problems the lower
Neuropathic urinary tract

For Healthcare Professional Use only


MECHANISM OF ACTION ALPHA BLOCKER AND 5 ARI

5 – ARI Alpha blocker


Reduces Relaxes the
prostate volume smooth muscle

For Healthcare Professional Use only


Alpha-blockers

• Relax the smooth muscle of the prostate and bladder neck

Bladder
Enlarged
prostate Urethra Relaxed
gland smooth
Open
lumen muscle

Emberton M et al. Int J Clin Pract 2008;62:1076-86.


Alpha-blockers

Appropriate for men with moderate-to-severe LUTS

• Common molecules: tamsulosin, doxazosin, alfuzosin, silodosin, terazosin

• Provide rapid (hours to days) relief of symptoms and improved urinary flow

• Alpha-blockers can reduce both storage and voiding LUTS

• Seem to be more efficacious in patients with smaller prostates (<40 mL) in


longer-term studies

• All alpha-blockers have a similar efficacy in appropriate doses

• No demonstrable effect on:


- Prostate volume
- Reducing long term risk of AUR
- Reducing long term risk of BPH-related surgery
Not all treatment options may be available in all countries
Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#.
Alpha-blockers tolerability

• Observed side effects are mostly related to vasodilating


effects:
– Asthenia
– Dizziness
– Orthostatic hypotension

• Intra-operative floppy iris syndrome occurring in cataract


surgery only recently recognised as related adverse effect

• No apparent negative impact on libido

• Small beneficial effect on erectile function

• Occasional incidence of abnormal ejaculation

Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#.
5-alpha reductase inhibitors (5-ARI)
• Molecules: dutasteride and finasteride
• Inhibit the conversion of testosterone to dihydrotestosterone which is the
androgen predominantly responsible for prostate growth

Dutasteride inhibits type 1 5AR

Bladder
Enlarged
prostate gland Urethra
Type1
5AR

–Testosterone
Testosterone Dihydrotestosterone

Type2
5AR Shrunken
Open
prostate gland
lumen

Both dutasteride and finasteride


inhibit type 2 5AR

– Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#.
5-alpha reductase inhibitors (5-ARI)

Appropriate for men with moderate-to-severe LUTS and an enlarged


prostate and/or elevated PSA concentration considering long-term treatment

• Symptoms and urinary flow improved after a minimum treatment


duration of at least 6-12 months
• After 2-4 years of treatment:
- IPSS improved by 15-30%
- Prostate volume decreased by 18-28%
- Qmax increased by 1.5-2.0 mL/sec
• Symptom improvement depends on initial prostate size

• Reduce the risk of AUR and BPH-related surgery

• About 50% decrease in circulating PSA levels


Qmax: peak urinary flow

Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#.
5-alpha reductase inhibitors (5-ARI) tolerability

• Most commonly reported side effects relate to sexual function


– Erectile dysfunction
– Decrease libido
– Ejaculation disorders
• The incidence of sexual dysfunction and other adverse events
is low and decreases with treatment duration
• Gynaecomastia is observed in 1-2% of patients
• No causal relationship of 5-ARIs with high-grade prostate
cancer has been proven
• No identified association between 5-ARIs and increased
cardiovascular side effects

Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#.
Combination therapy
Alpha-blocker + 5-ARI

• The most thoroughly studied combination1-3

Alpha-
5-ARI
blocker

 Improve symptoms/flow 
 Onset of symptom relief in 1–2 weeks 
 Prevent symptomatic progression (short term) 
 Sustained symptomatic benefit 
 Reduce PV 
 Maintain reductions in PV 
 Reduce long-term risk of AUR and surgery 

1. Madersbacher S et al. Eur Urol 2004;46:547-54; 2. Madersbacher S et al. Eur Urol 2007;51:1522-33; 3. Roehrborn C, Heaton J. Eur Urol
2006;5(Suppl);716-21.
Alpha-blocker + 5-ARI combination therapy

Combination treatment with an alpha-blocker and a 5-ARI could be offered


to men with moderate-to-severe LUTS and risk of disease progression1

• Synergistic efficacy to improve symptoms and prevent disease


progression
• Dutasteride + tamsulosin The only combinations assessed for
finasteride + doxazosin efficacy and safety in long-term RCTs2

• Dutasteride + tamsulosin The only combination with evidence in


BPH patients at risk of progression3*

• The adverse events observed during combination treatment were


typical of alpha-blockers and 5-ARIs and of higher frequency with
combination therapy
RCT: Randomised controlled trials *Moderate to severe symptoms PV≥30 mL and PSA ≥1.5 ng/mL
1. Gravas S et al. Treatment of Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#.; 2. Füllhase C et al. Eur Urol 2013;64:228-43; 3. Siami P et al. Contemp Clin Trials
2007; 28:770-9.
MTOPS and CombAT studies demonstrated the
benefit of 5-ARI and α1-blocker combination therapy

Primary endpoint
AUA-SS/IPSS and Qmax

VA-COOP1 PREDICT1 CombAT2,3


1 year 1 year 2-4 year
1229 patients 1095 patients 4844 patients
Terazosin 10 mg/ Doxazosin 4-8 mg/ Tamsulosin 0.4 mg/
Finasteride 5 mg Finasteride 5 mg Dutasteride 0.5 mg

1995 1996 2001 2003 2010 2015

ALFIN1 MTOPS1 CONDUCT4


0.5 year 6 year 2 year
1051 patients 3047 patients 742 patients
Alfuzosin 2x5 mg/ Doxazosin 4-8 mg/ (Fixed dose combination of dutasteride 0.5 mg and tamsulosin 0.4
Finasteride 5 mg Finasteride 5 mg mg)/
Watchful Waiting with initiation of tamsulosin 0.4 mg if symptoms
did not improve

Primary endpoint Primary endpoint


Clinical progression Change in IPSS from baseline

Dutasteride + Tamsulosin The only [5ARI + α1-blocker] combinations assessed for efficacy and safety in
Finasteride + Doxazosin long-term RCTs

1. Füllhase C, et al. Eur Urol 2013 Aug;64(2):228-43; 2. Roehrborn CG, et al. Eur Urol 2010 Jan;57(1):123-31; 3. Roehrborn CG, et al. J Urol 2008 Feb;179(2):616-21. 4. Roehrborn CG et al. BJU Int 2015;116:450–459

For Healthcare Professional Use only


Guidelines vs Clinical Practice: overall evolution of
5ARI recommendation and use in main EU countries

EAU guidelines recommend...

• 5ARI (finasteride) • 5ARIs (fin and dut) • 5ARI (fin and dut) 5ARI and 5ARI+AB
• 5ARI+AB was not • 5ARI+AB (MTOPS) • 5ARI+AB (MTOPS with specific thresholds
recommended and CombAT ) for PV and PSA

20014 20045 2010 20126

Italy Spai UK France Germany


n
Prescription Index (PI) %

5ARI treatment in appropriate patients remains variable and low


despite extensive evidence supporting individualised treatment

Year

1. IMS MIDAS database 2001-2014; 2 Eurostat accessed on 20/01/16 through http://ec.europa.eu/eurostat/data/database; 3. Cornu JN, et al. Eur Urol 2010; 4. De la Rosette et al. EAU Guidelines on Benign Prostatic
Hyperplasia (2001); 5 Madersbacher S et al. Eur Urol 2004;46:547–554; 6. Oelke M et al Management of Male Lower Urinary Tract Symptoms (LUTS), incl. Benign Prostatic Obstruction (BPO) (2012)

For Healthcare Professional Use only


Personalised management of BPH
Take home messages

BPH is important due to its high prevalence, progressive


nature and impact on patients quality of life1,2

Not all BPH patients are the same.


Guidelines for the assessment of men with LUTS/BPH can
help GPs to define the clinical profile of patients and identify
those at risk of disease progression3

Many options are nowadays available to treat BPH patients.


Current evidence supports a personalised treatment
approach to BPH based on risk of disease progression3

1. Rosenberg MT et al. Int J Clin Pract 2007;61:1535-46; 2. Carballido J et al. Int J Clin Pract 2011;65:989-96; 3. Gravas S et al. Treatment of
Non-neurogenic Male LUTS European Association of Urology Guidelines 2016; accessed on 28-04-16 through
http://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#.
Combination Therapy

Selected
Combination therapy of Cases: higher prostate volume
BPH maybe superior in
IPSS outcome,
especially in chronic higher PSA
use. But it also poses concentration
more risks.
advanced age

higher PVR
Combination therapy of
BPH can have benefits
on selected cases. lower urinary flow

For Healthcare Professional Use only