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Benign Prostatic Hyperplasia (BPH)

Disease and Management

What is prostate? gland of the male mammalian reproductive The prostate is an exocrine
system. Function Store and secrete a clear, slightly alkaline (pH 7.29) fluid The prostate also contains some smooth muscles that help expel semen during ejaculation

What is BPH?

A nodular growth of the peri-urethral prostatic tissue May result in urethral compression, and cause a group of symptoms often referred to as "prostatism or LUTS

BPH Prostate

Cancer Prostate

BPH starts in the inner part of the gland and as it enlarges, it squashes the outer part of the gland into a fairly thin shell, called a capsule. BPH never spreads outside the gland.

These usually develop in the outer part of the gland and may not block the urethra at first. Many men with tumors coincidently have BPH in the inner part of the gland, and often these BPH symptoms leads to the cancer being discovered.

The 2 components
Static Component

Dynamic Component

Normal

Hyperplastic

Increase in prostate bulk

Increase in smooth muscle tone

What are the symptoms of BPH?

OBSTRUCTIVE SYMPTOMS - CAUSED BY BPH Poor stream The urine flows with less force, traveling only a short distance, sometimes straight down. Having to wait for the urine to start flowing. The flow of urine continues after the main stream has finished, sometimes in spurts or dribbles. Occasionally a second large volume of urine is passed After finishing, there is a feeling that there is still urine in the bladder.

Hesitancy Terminal dribbling

Incomplete emptying

IRRITATIVE SYMPTOMS DUE TO OVERACTIVITY OF THE BLADDER Frequency Nocturia Urgency An abnormally short time between passing urine. Being woken in the night by the need to pass urine. Being unable to hold on after feeling the need to pass urine. Can lead to urine leaking (incontinence).

With irritative symptoms, a sensation of incomplete bladder emptying sometimes occurs, even though the bladder is empty

How is BPH diagnosed?


AUA Symptom Score (questionnaire) Medical history Physical examination Prostate exam Urinalysis PSA blood test Transrectal ultrasound of prostate

The physical examination


Abdominal examination
Bladder examination with percussion of the bladder

Digital Rectal Examination (DRE)+++


Fundamental method for assessing the shape and volume of prostate, benign feels smooth.

Benign vs Malignant

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PSA Alkaline phosphatase to detect metastasis Urinary cytology to detect malignant cells Plain pelvic x-rays to detect bony metastases

Digital Rectal Examination (DRE)

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CONDITION

DRE FINDING

Prostatitis BPH

soft, boggy and tender enlarged, smooth, firm anatomical groove may be felt

Prostate Cancer

hard nodular, craggy feel to gland loss of normal anatomical groove

The I-PSS - symptom assessment


The I-PSS is based on the answers to 7 questions concerning urinary symptoms. Each question is assigned points from 0 to 5 indicating increasing severity. The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic).
Mild Moderate Severe 0-7 8-19 20-35

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The I-PSS Questionnaire (1)


Patient Name: Date:
Not at all Less than Less than About More than 1 time half the half the half the in 5 time time time About Not at all Less than More Less 1 time in 5 than half than half half the time the time the time Almost always Almost always

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Your score Your score

1. Incomplete emptying

Over the past month, how often have you had a sensation of sensation of not emptying your bladder completely after you finish urinating?

2. Frequency

Over the past month, how often have you had to urinate again less than two hours after you finished urinating?

0
0

1
1

2
2

3
3

4
4

5
5

3. Intermittency

Over the past month, how often have you found you stopped and started again several times when you urinated?

Uroflowmetry
Measures peak urinary flow rate (Qmax), voided volume and micturition time. A micturition volume of at least 150ml is required for an adequate analysis Interpretation of maximum urinary flow rate values:
Normal Equivocal Obstructed > 15 ml/s 10-15 ml/s < 10 ml/s

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Post-void residual urine


Useful in the initial diagnostic of BPH and in the follow-up Determination is best performed by transabdominal ultrasonography

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Abnormal if > 50 - 100 ml on at least 2 measurements (large intra-individual variability) Related to bladder outflow obstruction but also detrusor failure, aging and sensory abnormalities

BPH: 3 treatment options

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Watchful Waiting Medical Treatment

Surgery

-blockers

5-reductase inhibitors

Medical Treatment
Symptomatic relief of BPH in patients without an absolute indication of surgery Patients in whom surgery is contraindicated Patients unwilling to go for surgery Patients awaiting sugery Prophylaxis for acute urinary retention

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-blockers act on the dynamic component of BOO

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They reduce the sympathetic tone of the prostate and the urethra

Types of Alpha blockers

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Uroselective (new generation) -blockers mainly have effect on BOO

Non-uroselective (old generation) -blockers also have an effect on blood pressure

5-reductase inhibitors act on the static component of BOO

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By inhibiting the production of DHT, they reduce the size of the prostate

Alfuzosin (Uroselective alpha blocker)

Key Findings from Clinical Trials

IC.ALF.04.06.03

Pg 21

Qmax: Pooled analysis


3.0 Change in Qmax (ml/s) 2.5 2.0 1.5 1.0 0.5 0 D0 D14 D28 D56 D84

Alfuzosin 10mg OD (n=473) Placebo (n=482)

p=0.02

p=0.001 p=0.25 p<0.0001

Pooled analysis of 3 double-blind placebo-controlled studies


IC.ALF.04.06.03

Roehrborn C. BJU Int 2003; 92: 25726122 Pg

LUTS: Pooled analysis


0 Change in IPSS from D0 -1 -2 -3 -4 -5 -6 -7 D0 p<0.001 D28 p=0.002 D56 p<0.001 D84

Alfuzosin 10mg OD (n=473) Placebo (n=482)

Pooled analysis of 3 double-blind placebo-controlled studies


IC.ALF.04.06.03

Roehrborn C et al. BJU Int 2003; 92: 257261 Pg 23

Efficacy whatever the prostate size


2.0 Change in Qmax 1.5 1.0 0.5 0.0 < 30ml 3040ml 4060ml

Qmax
0 Change in IPSS -1 -2 -3 -4 -5 -6 <30ml

LUTS

3040ml 4060ml

Alfuzosin 10mg OD
Pooled analysis of 3 double-blind placebo-controlled studies
IC.ALF.04.06.03

Roehrborn C et al. BJU Int 2003; 92: 257261 Pg 24

Alfuzosin 10mg OD: Key Findings


q

Fast improvement of flow rate and LUTS whatever the prostate size

Good cardiovascular tolerability

IC.ALF.04.06.03

Pg 25

Safety Profile Alfuzosin 10 mg OD vs. Tamsulosin


Cardiovascular tolerability Placebo n=153 Vasodilatory events n(%) Dizziness Headache Hypotension Syncope Malaise Alf 10 mg n=154 5.8% 1.9% 0 0 0 Alf 15 mg n=158 7.0% 2.5% 0.6% 1.3% 0.6% Tam 0.4 mg n=158 1.9% 4.4% 0.6% 0.6% 0

3.9% 3.3% 0 0 0

Others Asthenia / 2.0% 2.6% 6.3% 3.8% Efficacy of fatigue Alfuzosin 10 mg OD on Qmax and LUTS was similar to tamsulosin, 1.3% 0.6% with no added Somnolence benefit of the 15 mg dosage vs the 10 mg dosage
IC.ALF.04.06.03

Nordling J. BJU Int. 2005 May; 95 (7): 1006-12 Pg 26

Blood pressure changes


Supine
0 Change in blood pressure -1 -2 -3 -4 -5 -6 Placebo
IC.ALF.04.06.03

Standing
DBP SBP DBP

SBP

Alfu 10 mg

Alfu 15 mg

Tamsu 0.4 mg

Nordling J. BJU Int. 2005 May; 95 (7): 1006-12 Pg 27

BP changes in elderly ( 65 years)


Supine
0 Change in blood pressure -1 -2 -3 -4 -5 -6 -7 -8 Placebo
IC.ALF.04.06.03

Standing
DBP SBP DBP

SBP

Alfu 10 mg

Alfu 15 mg

Tamsu 0.4 mg

Nordling J. BJU Int. 2005 May; 95 (7): 1006-12 Pg 28

BP changes in men with anti-hypertensive co-medication


Supine
Change in blood pressure 0 -1 -2 -3 -4 -5 -6 -7 -8 Placebo
IC.ALF.04.06.03

Standing
DBP SBP DBP

SBP

Alfu 10 mg

Alfu 15 mg

Tamsu 0.4 mg

Nordling J. BJU Int. 2005 May; 95 (7): 1006-12 Pg 29

Surgical treatment

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Indications of surgery
Acute urinary retention Renal failure secondary to BPH Recurrent bladder stones A large residual urine Overflow incontinence Recurrent urinary tract infections Very large prostates (generally bigger than 70 grams) are

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too large to safely perform transurethral prostatectomy, and an open retropubic prostatectomy may be required.

Complications of surgery
Hemorrhage Post operative infection Recurrence: rare, 10-15 yrs Incontinence: muscle damage Dysuria: urethral stenosis Sexual dysfunction: retrograde ejaculation

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TURP

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(transurethral resection of the prostate)

Gold Standard of care for BPH Uses an electrical knife (electro-cautery) to surgically cut and remove excess prostate tissue, tissue and blood vessls sealed The resectoscope, which is about 12 inches long and 1/2 inch in diameter, contains a light, valves for controlling irrigating fluid, and an electrical loop that cuts tissue and seals blood vessels

The Gold standard- TURP

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Advantages
Widely available Effective Long lasting

Disadvantages
Greater risk of side effects and complications 1-4 days hospital stay 1-3 days catheter

Possible side effects of TURP


Impotence Incontinence Bleeding

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Minimally Invasive Therapy


Transurethral Microwave Therapy (TUMT) Transurethral Needle Ablation (TUNA) Green light laser

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Thank you!

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