1. Current Strategic on BPH Management – Combination Therapy
Dr. Boyke Subali, SpU
RSU. A. Wahab Sjahranie - Samarinda

2. Current Treatment of BPH
Sub Tittle
Prevalence
When should BPH be considered
as a disease?
Current Treatment of BPH

3. Prevalence of Histologic BPH Increases with Age
Prevalence of histological benign prostatic hyperplasia (BPH) by age group in nine autopsy series from around the world.
This slide shows age-stratified prevalence of BPH from 9 autopsy studies in the United States, England, Austria, Norway, Denmark, China, Japan, and India, with the smoothed line showing the average
Prevalence increases rapidly in the 4th decade of life, reaching nearly 100% in the 9th decade
Age-specific autopsy prevalence is strikingly similar in all populations studied, regardless of ethnic and geographic origin
Roehrborn CG, et al.International Journal of Impotence Research.2008; 20: S11–S18

4. BPH influenced Daily activities
Garraway WM, et al. Br J Gen Pract. 1993;43(373):

5. When should BPH be considered as a disease?
Yes!
Bothersome symptoms?
Prostatic parc

6. Benign Prostate Hyperplasia (BPH)
Benign prostatic hyperplasia (BPH) is a pathologic process that contributes to, but is not the sole cause of, lower urinary tract symptoms (LUTS) in aging men
Benign prostatic hyperplasia is defined histologically as a disease process characterized by stromal and epithelial cell hyperplasia.
Originates from transition zone
AUA Guideline. J Urol.2003;170:
Roehrborn CG. International Journal of Impotence Research.2008;20:S11–S18
Lee KL et al. J Urol 2004;172:1784–1791

7. BPH is characterised by non-malignant enlargement of the prostate
Normal
BPH
Hypertrophied detrusor muscle
Bladder
BPH involves a gradual enlargement of the prostate, such that bladder outflow becomes increasingly obstructed.1,2
This enlargement firstly develops in the peri-urethral transition zone of the prostate.2,3
The detrusor muscle of the bladder responds to this obstruction by hypertrophy, trabeculation, replacement of muscle with collagen and ultimately loss of efficiency.4
References
Anderson JB et al. Eur Urol 2001;39:390–399.
Wilson JD. Am J Med 1980;68:745–756.
Bartsch G et al. Eur Urol 2000;37:367–380.
Haas CA et al. Lepor H (ed). Prostatic Diseases. WB Saunders 2000:75–79.
Enlargement of the prostate
Prostate
Obstructed urinary flow
Urethra
Adapted from Kirby RS et al. Benign Prostatic Hyperplasia. Health Press, Oxford, 1999 available at:

8. BPH is caused by an imbalance of cell proliferation (growth) and apoptotic (death) signals – leads to increase in number of prostate cells and prostate size
Serum testosterone (T)
Serum DHT T
Prostate
cell
5α-reductase types 1 and 2
DHT
Growth
factors
DHT-androgen receptor complex
Although the precise role played by DHT in BPH is not yet elucidated, it appears that, via the mediation of androgen receptors, DHT has a dual function in cell proliferation and differentiation.1
Current evidence indicates that DHT acts indirectly via the modulation of transcription of growth factors to influence the expression of genes involved in cell proliferation and apoptosis, and directly to induce cell differentiation.1
The development and progression of BPH is thought to result from an imbalance of these proliferative, differentiating and apoptotic signals, which are regulated, in part, by DHT.1
Reference
1. Anderson JB et al. Eur Urol 2001;39:390–399.
Cell death
Increased
cell growth
Unbalanced
Adapted from Kirby RS, McConnell. Benign Prostatic Hyperplasia. Health Press Ltd, 1999

9. BPH, LUTS, BPE and BOO Clinical, anatomical, and pathophysiological changes
BPH = Benign Prostatic Hyperplasia
Histological: stromoglandular hyperplasia
May be associated with
Clinical: presence of bothersome LUTS2
Anatomical: enlargement of the gland (BPE = Benign Prostatic Enlargement)2
Pathophysiological: compression of urethra and compromise of urinary flow (BOO = Bladder Outlet Obstruction)2
All Men
>40 y
Histological BPH
BPE
Enlargement
LUTS/
Bother `
BOO
Obstruction
[Dr. Roehrborn transcript page 7]
[Changed “Anatomical” to “Anatomic” and “Pathophysiological” to “Pathophysiologic” for consistency throughout – “al” not used]
The definition of BPH is based on prostate size, symptoms, and obstruction.1
BPH may be associated with clinical signs, anatomic findings, and physiologic or pathophysiologic outcomes.1
Histologically, BPH is characterized by stromoglandular hyperplasia.2
Clinically, the patient has bothersome LUTS or evidence of lower urinary tract deterioration or upper urinary tract damage.1
Anatomically, enlargement of the prostate gland or an enlarged transition zone can be demonstrated objectively.1
Pathophysiologically, compression of the urethra leads to obstruction, with compromised urinary flow.1
Nordling C, Artibani W, Hald T, et al. Pathophysiology of the urinary bladder in obstruction and ageing. In: Chatelain C, Denis L, Foo KT, et al, eds. Benign Prostatic Hyperplasia. Plymouth, UK: Health Publications Ltd; 2001:
Roehrborn C (reviewer). Focus on lower urinary tract symptoms: nomenclature, diagnosis, and treatment options. Rev Urol. 2001;3:
Nordling J et al. In: Chatelain C et al, eds. Benign Prostatic Hyperplasia. Plymouth, UK: Health Publication Ltd; 2001: 9

10. BPH can cause lower urinary tract symptoms (LUTS)
BPH symptoms may include:
Voiding symptoms, caused by an enlarged prostate
Weak urinary stream
Prolonged voiding
Abdominal straining
Hesitancy
Intermittency
Incomplete bladder emptying
Terminal and post-void dribbling
Storage symptoms, which can result from enlarged prostate or overactive bladder (OAB)
Frequency
Nocturia
Urgency
Incontinence
Associated symptoms of BPH include:
Dysuria
Haematuria
Haematospermia
LUTS are not specific to BPH – not all men with LUTS have BPH and not all men with BPH have LUTS

11. Diagnostic tests recommended by the EAU BPH guidelines
Medical history
Symptom score
Physical examination (incl. DRE)
PSA
Creatinine measurement*
Urinalysis
Flow rate**
Post-void residual volume**
*Not recommended by the AUA guidelines
** Considered optional in the AUA guidelines
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554
AUA Practice Guidelines Committee. J Urol 2003; 170: 530–547

12. Symptoms score Evaluating symptom severity is an important part of the
initial assessment
Symptom severity is probably best assessed through the use of a validated symptom score
The internationale standard instrument is the International Prostate Symptom Score (IPSS)
The IPSS comprises of 8 questions:
7 questions about the severity of symptoms
These are identical to the 7 questions of the AUA Symptom Index*
1 question on global quality of life
Evaluation of symptom severity is an important part of the initial assessment and helpful in allocating treatment and in predicting and monitoring the response to therapy.1
Probably the best way to assess symptom severity is with a validated symptom score; the International Prostate Symptom Score (IPSS) has become the international standard.1
Reference
1. EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554.
*The AUA guidelines recommend use of the AUA-SI (7 questions)
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554
AUA Practice Guidelines Committee. J Urol 2003; 170: 530–547

13. Mixed – about equally satisfied & dissatisfied
IPSS questionnaire
Over the past month, how often have you…
Not at all
Less than 1 time in 5
Less than half the time
About half the time
More than half the time
Almost always
YOUR SCORE
1. …had a sensation of not emptying your bladder completely after you finish urinating? 1 2 3 4 5
2. …had to urinate again less than two hours after you finished urinating?
3. …stopped and started again several times when you urinated?
4. …found it difficult to postpone urination?
5. …had a weak urinary stream?
6. …had to push or strain to begin urination?
7. Over the past month, how many times did you most typically get up to urinate from the time you went to bed at night until the time you got up in the morning?
None
Once
Twice
3 times
4 times
5 times or more
TOTAL
8. QUALITY OF LIFE DUE TO URINARY SYMPTOMS
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
Mostly satisfied
Mixed – about equally satisfied & dissatisfied
Mostly dissatisfied
Unhappy
Terrible 6
There are 7 questions in the IPSS questionnaire with each question answered on a scale of 0 to 5.1
There is also an eighth stand alone question to determine the impact on quality of life for the patient.1
Reference
1. EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554.

14. Total IPSS indicates symptom severity
0–7
Mild
8–19
Moderate
20
Severe
There are 7 questions in the IPSS questionnaire with each question answered on a scale of 0 to 5, therefore the total score ranges from 0−35.1
Three categories of symptom severity are described: mild 0−7, moderate 8−19 and severe 20−35.1
There is also an eighth stand alone question to determine the impact on quality of life for the patient.1
Reference
1. EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554.
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554

15. Physical examination Physical examination during the initial
assessment of a man with LUTS suggestive of
BPH should include:
Focused neurological examination
Digital rectal examination (DRE)
To help evaluate prostate size
To help exclude the presence of prostate cancer, as well as prostatitis and other pelvic pathologies
The physical examination is carried out to detect prostate or rectal malignancy, to evaluate anal sphincter tone, and to rule out any neurologic problems that may cause the presenting symptoms.1
DRE routinely underestimates the size of the prostate measured by either transrectal ultrasonography (TRUS) or magnetic resonance imaging (MRI). The degree of underestimation increases with increasing prostate size.1
However, DRE may serve a useful role in threshold assessment, that is, in determining whether or not a patient has a prostate size of greater than 30 or 40 mL.1
Reference
Roehrborn CG. In Lepor H (ed). Prostatic Diseases. WB Saunders, 2000: 143–159.
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554

16. The clinical utility of PSA in assessing men with LUTS suggestive of BPH
Strong relationship between serum PSA and prostate volume enables
clinicians to estimate prostate size in BPH patients
Serum PSA thresholds can be used to predict the presence of a prostate >30ml or >40ml with sensitivity between 60-70% and specificity 70%.
Along with current prostate size, serum PSA provides prognostic
information about:
Prostate growth
Symptoms and bother deterioration
Sexual dysfunction
Flow rate worsening
Risk for AUR and surgery
In general higher levels of serum PSA indicate faster and greater risk for
progression
Roehrborn CG. Int J Impot Res 2008; 20: s19–26

17. Urinalysis Although benign prostatic obstruction is the most
frequent cause of LUTS in men, LUTS can also be
caused by urinary tract infection or bladder cancer
The absence of haematuria or pyruria on urinalysis helps to rule out these conditions
Guidelines recommend urinalysis to aid differential
diagnosis
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554
AUA Practice Guidelines Committee. J Urol 2003; 170: 530–547

18. Flow rate determined by uroflowmetry
Uroflowmetry is a simple non-invasive test that can reveal abnormal
voiding.
Serial flows (two or more) with a voided volume exceeding 150 ml are
recommended to obtain a representative flow test.
LUTS in the presence of a normal peak flow rate (Qmax= 15ml/s) are more likely to have a non-BPH-related cause, and men with Qmax <10 ml/sec are more likely to have urodynamic obstruction
Uroflowmetry is recommended by the EAU as part of the initial assessment of a man with LUTS, as well as being required prior to prostatectomy
Uroflowmetry is considered by the AUA to be an option following the initial patient evaluation
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554
AUA Practice Guidelines Committee. J Urol 2003; 170: 530–547

19. Measurement of post-void residual (PVR) volume
Measurement of PVR urine is recommended by the EAU guidelines and considered optional by the AUA
PVR volume is calculated by measurement of bladder height, width and length obtained by transabdominal ultrasonography
This is a simple, accurate and non-invasive method
Large PVR volumes (>200 mL) may indicate bladder dysfunction and predict a less favourable response to BPH treatment
Post-void residual volume (PVR) is defined as the volume of fluid remaining in the bladder immediately following a complete micturition.
In normal men this value is less than 12 mL.1
The reason for increased PVR in men with LUTS is not well understood.
Grossly increased PVR is strongly associated with a dilated paralysed bladder, and a decompensated detrusor muscle is thought to be the major aetiologic component of increased PVR in bladder outlet obstruction.1
Reference
Jepsen JV, Bruskewitz RC. In: Lepor H (ed). Prostatic Diseases. WB Saunders, 2000: 127–142.
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554

20. Current Treatment of BPH

21. Aims of treatment: EAU and AUA guidelines
The aim of therapy is to improve lower urinary tract symptoms (LUTS) and quality of life, and to prevent BPE/BPO-related complications such as urinary retention or upper urinary tract dilatation (EAU)
The patient's perception of the severity of the condition, as well as the degree to which it interferes with his lifestyle or causes embarrassment, should be the primary consideration in choosing therapy (AUA)
The EAU 2004 guidelines state that the aim of therapy is to improve lower urinary tract symptoms (LUTS) and quality of life, and to prevent benign prostatic enlargement (BPE)/benign prostatic obstruction (BPO)-related complications, such as urinary retention or upper urinary tract dilatation.1
Reference
1. EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554.
BPE = Benign prostatic enlargement
BPO = Benign prostatic obstruction
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554
AUA Practice Guidelines Committee. J Urol 2003; 170: 530–547

22. Treatment – initial management
Initial management of men with LUTS suggestive of BPH can be categorized into:
Watchful waiting
Medical therapy
Surgical management
Non-surgical intervention / Minimally invasive therapy
The following currently used treatments will be covered in this section: watchful waiting (including lifestyle modifications), medical therapy with 5-alpha-reductase inhibitors (5ARIs), alpha-blockers and combination therapy, surgical management, and non-surgical intervention (i.e. minimally invasive techniques.) The advantages and disadvantages of each therapy will be discussed.
Reference
1. EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554.
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554
AUA Practice Guidelines Committee. J Urol 2003; 170: 530–547

23. Management The following are important components of WW: Education
Reassurance
Periodic monitoring
Lifestyle modifications
It is customary for watchful waiting to include the following management components: education, reassurance, periodic monitoring and lifestyle advice.1
Education and reassurance can be accomplished by providing information about BPH to patients. Information aids for men with BPH have been shown to increase patients’ participation in decision-making, and reduce anxiety and decisional conflict.2
Patients should be monitored periodically by reassessment of symptom level, physical findings, routine laboratory testing, and optional urologic diagnostic procedures. If the patient’s symptoms progress to moderate or severe levels, alternative treatment options should be discussed with the patient.3
Patients following a watchful waiting strategy should also be instructed in lifestyle modifications such as behavioural techniques to reduce symptoms, e.g. limiting fluid intake after dinner and avoiding decongestants.3
References
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554.
Brown CT, Emberton M. Curr Opin Urol 2004; 14: 7–12.
Roehrborn CG. In: Lepor H (ed). Prostatic Diseases. WB Saunders, 2000: 143–159.
Brown C et al. Curr Opin Urol 2004; 14: 7–12

24. Medical therapy
The following medical treatments are recommended for BPH treatment :
Alpha blockers (as monotherapy)
5 alpha-reductase inhibitors - 5ARIs (as monotherapy)
Combination therapy
EAU BPH guidelines. Madersbacher S et al. Eur Urol 2004; 46: 547–554
AUA Practice Guidelines Committee. J Urol 2003; 170: 530–547

25. Need for a new approach
Dependence on alpha-blocker monotherapy is failing a proportion of men with BPH
Need to move away from ‘one-size-fits-all’ medicine to a more personalised approach
Need for tailored solutions consistent with treatment guidelines
Appropriate treatment needed for men with moderate symptoms onwards, prostate volume ≥30 ml and PSA ≥1.5 ng/ml
Emberton M et al. BJU Int Jan 25. doi: /j X x

26. What is the optimal treatment for men with moderate symptoms onwards, prostate volume ≥30 ml and PSA ≥1.5 ng/ml?
CombAT study provides insights into treatment of men with moderate symptoms onwards, prostate volume ≥30 ml and PSA ≥1.5 ng/ml
Entry criteria for CombAT:
Male aged ≥50 years
Diagnosis of BPH by history and DRE
IPSS ≥12 (moderate-to-severe symptoms)
Prostate volume ≥30 cc by TRUS
Serum PSA 1.5–10.0 ng/ml
Two voids at screening with Qmax >5 and ≤15 ml/sec (moderate-to-severe impairment) and minimum voided volume of ≥125 ml
Siami P et al. Contemp Clin Trials 2007;28:770–779

27. What can we learn from the CombAT data?
What benefit does combination therapy with dutasteride and tamsulosin have on:
Symptoms?
Quality of life?
Risk of long-term complications such as AUR and BPH-related surgery?

28. Adjusted mean change from baseline in IPSS
Superior symptom relief with combination therapy with dutasteride and tamsulosin versus either monotherapy
0.0
-1.0
-2.0
-3.0
-4.0
-5.0
-6.0
-7.0
-8.0
p <0.001 combination versus tamsulosin
p <0.001 combination versus dutasteride
Symptom improvement with combination therapy starts as rapidly as tamsulosin monotherapy
-2.8
-3.4
Symptom improvement of at least 3 units is generally considered to be perceptible for the patient and accepted as the minimum threshold of clinical relevance
12/6/A
-3.8
-3.8
-3.8
-4.0
-4.1
-4.0
-4.0
Adjusted mean change from baseline in IPSS
-4.2
-4.2
-4.4
-4.3
-4.5
-4.5
-4.4
-4.4
-4.7
-4.8
-4.5
-4.8
-4.8
-4.8
-4.9
-5.0
-4.9
-5.1
-5.2
-5.2
-5.2
-5.4
-5.3
-5.3
-5.4
-5.3
-5.6
-6.0
-6.0
-6.2
-6.2
-6.2
-6.4
-6.3
-6.3
-6.3
-6.5
-6.4
-6.3
12/6/B
Baseline 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48
Study month
Combination (n = 1575)
Dutasteride (n = 1592)
Tamsulosin (n = 1582)
Roehrborn CG et al. Eur Urol 2010;57:123–131; Barry MJ et al. J Urol 1995;154:1770–74 28

29. Patients with LUTS consider storage symptoms to be most bothersome symptoms
Bother index
n=1803 to 2046, depending on the symptom
Häkkinen JT et al. Eur Urol 2007;51:473–478

30. Combination therapy with dutasteride and tamsulosin superior to both monotherapies at 4 years: Storage symptoms
Adjusted mean change from baseline in IPSS storage score * *
*p<0.001 versus combination
Montorsi F et al. BJU Int 2011 Feb 23; DOI:  /j X x
CombAT Year 4 Long Presentation 15-Apr-2009 30

31. Many men with moderate-to-severe symptoms (IPSS ≥8) have both storage and voiding symptoms: findings from a population-based survey
Prevalence of LUTS subtypes (%)
Age (years)
Storage symptoms: sum of scores on IPSS items 2, 4 and 7 was ≥4 and score on item 4 (i.e. urgency) was ≥1
Voiding symptoms: sum of scores on IPSS items 1, 3, 5 and 6 was ≥5
Mixed symptoms: criteria met for both storage and voiding symptoms
Glasser DB et al. Int J Clin Pract 2007;61:1294–1300

32. Combination therapy with dutasteride and tamsulosin superior to both monotherapies at 4 years: Voiding symptoms
Adjusted mean change from baseline in IPSS voiding score * *
*p<0.001 versus combination
Montorsi F et al. BJU Int 2011 Feb 23; DOI:  /j X x
CombAT Year 4 Long Presentation 15-Apr-2009 32

33. Symptoms: What can we conclude?
Over 4 years, combination therapy with dutasteride and tamsulosin provided significantly superior symptom improvement compared with either monotherapy for:
Total symptoms
Storage symptoms
Voiding symptoms
Symptom improvement starts as rapidly as tamsulosin monotherapy

34. The BII
A disease-specific 4-item instrument that measures the impact of LUTS on
Physical discomfort
Worry about health
Degree of bother
Limitations of daily activities
Total scores range from 0 (no impact) to 13 (highest negative impact)
Montorsi F et al. Int J Clin Pract 2010;64:1042–1051

35. BII: combination therapy with dutasteride and tamsulosin superior to both monotherapies at 4 years
Adjusted mean change from baseline in BII
Mean baseline BII = 5.3
p≤0.008 combination versus tamsulosin
p≤0.003 combination versus dutasteride
-1.2
-1.8
-2.2
Month
Tamsulosin
Dutasteride
Combination
Montorsi F et al. Int J Clin Pract 2010;64:1042–1051

36. 12 questions covering six areas
The PPSM questionnaire was developed by GSK to assess patient satisfaction with treatment in the CombAT study
12 questions covering six areas
Control of urinary symptoms
Strength of urinary stream
Two aspects of pain of urination
Effect on usual activities
Overall satisfaction
Whether the respondent would ask their doctor for this medication
PPSM total score ranges from 7 (best) to 49 (worst)
Question 12: possible responses are yes, no and not sure
Montorsi F et al. Int J Clin Pract 2010;64:1042–1051; Black L et al. Health Qual Life Outcomes 2009;7:55

37. PPSM total score: combination therapy with dutasteride and tamsulosin superior to both monotherapies at 4 years
Adjusted mean change from baseline in PPSM total score
Mean baseline PPSM total score = 25
p<0.001 combination versus tamsulosin
p<0.001 combination versus dutasteride
-4.1
-5.5
-7.0
Month
Tamsulosin
Dutasteride
Combination
Montorsi F et al. Int J Clin Pract 2010;64:1042–1051

38. Satisfaction with treatment (PPSM Q11): combination therapy with dutasteride and tamsulosin superior to both monotherapies at 4 years
Percentage of patients satisfied with treatment
80%
74%
69%
p<0.001 combination versus tamsulosin
p≤0.002 combination versus dutasteride 0%
Month
Tamsulosin
Dutasteride
Combination
Montorsi F et al. Int J Clin Pract 2010;64:1042–1051

39. PPSM Q12: Would you ask your doctor for the medication you received in the study?
Percentage of patients responding ‘Yes’ * *
*p<0.01 versus combination
Montorsi F et al. Int J Clin Pract 2010;64:1042–1051

40. QoL: What can we conclude?
Combination therapy with dutasteride and tamsulosin provides significantly superior improvements in patient-reported QoL and treatment satisfaction than either monotherapy
Improved overall QoL (IPSS Q8)
Reduced impact of BPH (BII)
Improved treatment satisfaction (PPSM)
Superiority of combination therapy versus both monotherapies was sustained out to 4 years

41. CombAT 4-year primary endpoint: Time to first AUR or BPH-related surgery16 14 12 10 8 6 4 2
Combination
Dutasteride
Tamsulosin
Percent of patients
8 months 12 24 36 48
Time (months)
Combination Cumulative no. of events No. at risk
Dutasteride Cumulative no. of events No. at risk
Tamsulosin Cumulative no. of events No. at risk
Roehrborn CG et al. Eur Urol 2010;57:123–131

42. Conclusions
In men with moderate symptoms onwards with prostate volume ≥30 ml and PSA ≥1.5 ng/ml, CombAT shows that over 4 years, combination therapy with dutasteride and tamsulosin
Significantly improves symptoms and QoL versus either monotherapy
Significantly reduces the risk of AUR or BPH-related surgery versus tamsulosin monotherapy

43. Implications of CombAT study: What do these results mean for patients?
Men with BPH/LUTS may experience a substantial reduction in their quality of life
In many men, the progressive course of BPH raises the prospect of worsening symptoms, AUR and the need for surgery4
Major goals of BPH treatment include improvement of symptom scores, lowering risk of disease progression, improving patient-reported quality of life and treatment satisfaction1
In the CombAT study, combination therapy was associated with:
Improvement of symptoms2
Reduced risk of BPH clinical progression2
Reduced risk of AUR or BPH-related surgery2
Improved patient-reported health outcomes3
1Madersbacher S et al. Eur Urol 2004;46:547–554; 2Roehrborn CG et al. Eur Urol
2010;57:123–131; 3Montorsi F et al. Int J Clin Pract 2010; 4Emberton M et al. Int J Clin Pract 2008; 62: 18–26