BPH and Medical Treatment Options - United Health Services

Diagnosis and Management of
Benign
Prostatic
Beng Jit
(BPH)
Hyperplasia
Tan MD PhD
Department of Urology
United Health Services

BLADDER
PROSTATE
URETHRA
Anatomy of BPH
Normal BPH
Hypertrophied
detrusor muscle
Obstructed
urinary flow
Roehrborn CG, McConnell JD. In: Walsh PC et al, eds. Campbell’s Urology. 8th ed. Philadelphia, Pa: Saunders; 2002:1297-1336.
2002:1297 1336.

Top Top 10 10 Diagnosed Diagnosed Diseases
Diseases
in in Men Men Age Age ≥
50 50 Years
Years
Rank Disease
1-year prevalence (%)
(n = 963,452 personyears)
1
Coronary Artery
Disease/Hyperlipidemia
51.3
2 Hypertension 45.2
3 Diabetes Mellitus Type 2 17.5
4 Enlarged Prostate 13.5
5 Osteoarthritis 13.3
6 Arrhythmias 8.8
7 Cataract 8.6
8 Gastroesophogeal reflux disease 8.4
9 Bursitis 8.0
10 Prostate Cancer 7.8
Issa MM et al. Am J Manag Care. 2006;12(suppl):S83–S89.

Lower Urinary Tract Symptoms
Obstructive Symptoms
• Hesitancy
• Weak stream
• Straining to pass urine
• Prolonged micturition
• Feeling of incomplete
bladder emptying
• Urinary retention
(LUTS)
Kirby RS et al. Benign prostatic hyperplasia. hyperplasia.
Health Press, 1995.
Irritative Symptoms
•
•
•
•
Urgency
Frequency
Nocturia
Urge incontinence

Problems
LUTS 1,2
BPH
(Benign Prostatic
Hyperplasia)
BOO 3
(Bladder Outlet
Obstruction)
Consequences
Bothersome
Interference with daily
activities and sexual
function
AUR
Surgery
Nonfunctioning bladder
UTI
Stones
Renal failure
1. AUA Practice Guidelines Committee. JUrol.2003;170:530-547. 2. Rosen R et al. Eur Urol. 2003;44:637-649.
3. Lepor H, Lowe FC. In: Walsh PC et al, eds. Campbell’s Campbell s Urology. Urology.
8th ed. Philadelphia, Pa: Saunders; 2002:1337-1377.
2002:1337 1377.

% of men with sexual activity
in the last 4 weeks
MSAM-7
Older Men Are Still Sexually Active
100%
80%
60%
40%
20%
0%
92%
83% 83%
Total
65%
50-59 60-69 70-79
Sexually activity = Any activity that the participant
considered “sexual”
Rosen R. Multinational Survey of the Aging Male (MSAM-7). Presented at the Annual Meeting
of the American Urological Association; May 26, 2002; Orlando, Fla.
Age

MSAM-7: Sexual Activity Declines With
Increasing Severity of LUTS Independent
of Age
Average Number of Sexual
Activities per Month*
10
9
8
7
6
5
4
3
2
1
0
*Among total sample.
8.6
LUTS Effect
7.6
6.6
4.9
Age Effect
5.7
LUTS Effect
5.7
4.6
3.7
4.0
3.5
2.6
50-59 y 60-69 y 70-79 y
Rosen R. Multinational Survey of the Aging Male (MSAM-7). Presented at the
Annual Meeting of the American Urological Association; May 26, 2002; Orlando, Fla.
LUTS Effect
1.7
LUTS
None
Mild
Moderate
Severe

Average Erectile Function Score
(IIEF)*
30
20
10
0
MSAM-7: Erectile Function Declines
With Increasing Severity of LUTS
Independent of Age
LUTS Effect
22.3 21.0
18.9
15.0
Age Effect
19.3
LUTS Effect
18.3
15.9
12.6
15.2
13.2
10.3
50-59 y 60-69 y 70-79 y
Average score on a scale
from 1 to 30 (6 questions)
measured by IIEF
Per question: 1 = Negative to 5 = Positive
LUTS Effect
Base: Men sexually active/sexual intercourse during past 4 weeks, *as measured by IIEF.
Rosen R. Multinational Survey of the Aging Male (MSAM-7). Presented at the
Annual Meeting of the American Urological Association; May 26, 2002; Orlando, Fla.
7.5
LUTS
None
Mild
Moderate
Severe

Why Does BPH Progress
In Some But Not All Men?

•
•
•
•
Risk Factors for BPH Progression
Age 50 years or older
AUA-SI score > 7
Enlarged prostate (≥
PSA ≥
1.5
McConnell JD et al. N Engl J Med. 2003;349:2387−2398.
Roehrborn CG et al. Urology.1999;53:473−480.
30-40 ml.)

Prevalence (%)
100
90
80
70
60
50
40
30
20
10
0
Prevalence of
Histologic
Increases With Age
20-29 30-39 40-49 50-59
Age (yr)
60-69 70-79 80-89
BPH
Pradhan (1975)
Moore (1943)
Baron (1941)
Swyer (1944)
Harbitz (1972)
Fang-Liu (1991)
Franks (1954)
Holund (1980)
Karube (1961)
Roehrborn CG, McConnell JD. In: Walsh PC et al, eds. Campbell’s Urology. 8th ed. Philadelphia, Pa: Pa: Saunders; Saunders; 2002:1297-1336.
2002:

•
•
•
•
Risk Factors for BPH Progression
Age 50 years or older
AUA-SI score > 7
Enlarged prostate (≥
PSA ≥
1.5
McConnell JD et al. N Engl J Med. 2003;349:2387−2398.
Roehrborn CG et al. Urology.1999;53:473−480.
30-40 ml.)

Relationship Between Prostate Volume
and Serum PSA in Men with BPH
Prostate volume (mL)
65
60
55
50
45
40
35
30
1 2 3 4 5 6 7
Serum PSA (ng/mL)
Roehrborn CG et al. Urology. 1999;53:581–589.
75
70
65
60
55
50
Age (years)

Rate per 100 person-years
6
5
4
3
2
1
0
Cumulative Incidence of
Progression by Baseline PSA
P < 0.0001
Progression > 4-point rise
in AUA-SI score
McConnell JD et al. N Engl J Med. 2003;349:2387−2398.
P = 0.0003
PSA (ng/mL)
AUR
< 1.4
1.4−3.9
≥ 4.0
P < 0.0001

•
•
Treatment Options for BPH
Watchful waiting
Pharmacologic therapy
–
–
–
alpha-adrenergic blockers
(for BPH symptoms)
5-ARIs
combinations of the above
5-ARIs=5-alpha-reductase inhibitors
ILC=interstitial laser coagulation (also known as LITT)
TUIP=transurethral incision of prostate
TUMT=transurethral microwave thermotherapy
TUNA=transurethral needle ablation
TURP=transurethral resection of prostate
AUA Practice Guidelines Committee. J Urol. 2003;170:530-547.
•
•
•
Minimally invasive therapy
–
–
–
TUMT
TUNA
ILC
Less invasive surgery
– Laser vaporization
Major surgery
–
–
–
TURP (gold standard)
TUIP
Open surgery (prostatectomy)

Watchful Waiting/Active Surveillance
•
•
Patient is followed annually but receives
no active intervention for symptoms 1
Appropriate option for patients with mild
symptoms, and for many with moderate
to severe symptoms if they are not
bothered 1
1. AUA Practice Guidelines Committee. J Urol. 2003;170:530-547.
2. Brookes ST et al. BMJ. 2002;34:1059-1061.

Pharmacologic Therapy For BPH
–α-adrenergic blockers
–5α-reductase
inhibitors
–Combination therapy

Distribution of Alpha Receptors in
the Prostate and Bladder
Prostate Gland
Trigone
Internal Sphincter
External Sphincter
Detrusor
Pelvic Floor

Treatment Options: Alpha Blockers
•
•
Mechanism 1,2 :
–
–
Relax smooth muscle in
bladder neck and prostate
Improve urinary flow (Qmax) and bothersome symptoms
Agents indicated for
symptomatic BPH include1 :
–
–
–
–
–
Alfuzosin
Doxazosin
Silodosin
Tamsulosin
Terazosin
1. Kaplan S. Weill Medical College of Cornell University Reports on Men’s Urologic Health. 2006;1(1):1-8.
2. McConnell J, et al. N Engl J Med. 2003;349:2387-2398.
BPH = Benign Prostatic Hyperplasia

•
•
Differential Effects of α-Blockers
Doxazosin 1
–
–
on Blood Pressure
and Terazosin 2
Indicated for the treatment of hypertension
Initiated at a low dose to avoid a first-dose
phenomenon
(ie, syncope) 3
Alfuzosin 4 , Tamsulosin 5 and
–
–
Silodosin
Not indicated for the treatment of hypertension
Initial dose titration not required
1. CarduraR (doxazosin mesylate tablets) Prescribing Information, Pfizer Inc.
2 HytrinR (terazosin hydrochloride) Prescribing information, Abbott Laboratories.
3. Vallencien G. Urology. 1999;54:773-775.
4. UroxatralR (alfuzosin HCl extended release tablets) Prescribing Information, Sanofi-Synthelabo Inc.
5. FlomaxR (tamsulosin hydrochloride) Prescribing Information, Boehringer Ingelheim Pharmaceuticals Inc.

5α-Reductase
Proscar (Fineseteride)
Avodart (Dutasteride)
Inhibitors

Two 5α-Reductase (5AR) Isoenzymes
Convert Testosterone to DHT
Testosterone
Type II 5AR
Bartsch G et al. Eur Urol. 2000;37:367−380.
DHT
Type I 5AR Prostate
enlargement

Near Complete DHT Suppression
Requires Inhibiting Both 5AR Isoenzymes
Testosterone
Dutasteride
Type II 5AR
Type I 5AR
Bartsch G et al. Eur Urol. 2000;37:367−380.
Finasteride
DHT
Dutasteride
Prostate
volume
reduced

PSA Is Reduced in a Predictable Manner
with Dutasteride
Mean change in serum PSA (%)
20
10
0
-10
-20
-30
-40
-50
2.8 2.2
–9.2
-60
1 3 6 9 12 15 18 21 24
Baseline Month
Data on file, GlaxoSmithKline.
–35.7
5.5
–43.5
6.8
–48.6
10.7
15.8
Placebo
Dutasteride
–50.5 –52.4

��
Using PSA To Detect Cancer-Related
PSA Changes In Patients On 5-ARI’s
Establish new baseline PSA after 12
months of %-ARI treatment
–
Subsequent increases in PSA may indicate
noncompliance, prostate cancer, or other
prostate-related conditions that may need
evaluation

Rises in PSA after 6 Months on 5-ARI 5 ARI May
Be Indicative of Prostate Cancer
Median % Reduction in PSA
0
-10
-20
-30
-40
-50
-60
-70
Graph depicts 5-ARI treated patients only
0 6 12 18 24
Data on File GlaxoSmithKline
Treatment Month
No Prostate Cancer
Diagnosed (n=2124)
Prostate Cancer
Diagnosed (n=43)
-32.3
-59.3

REDUCE Trial Study Design ♦
Study Entry
(Screen Visit 1)
Randomization
(Visit 2)
2-year biopsy*
(Visit 6)
4-year biopsy*
(Visit 10)
Month: -7 -1 0 24 48
6-month
eligibility
window
Entry
biopsy
4-wk
Placebo
run-in
NOTE: All biopsies centrally evaluated
* Mandatory Transrectal Ultrasound (TRUS)-guided 10 core biopsies
Andriole G et al. J Urol. 2004;172:1314–1317.
4-year treatment period with
dutasteride 0.5 mg daily or placebo
For-cause biopsies may occur here
52
4-month
Follow-up

Preliminary Results from the
REDUCE Trial (Analysis Ongoing) ♦
• Primary Endpoint: 23% reduction in biopsy-detectable
prostate cancer with dutasteride vs. placebo over 4
years (P

Minimally Invasive/Surgical
Treatment Options For BPH

•
•
•
•
Principles of Thermotherapy
Blood supply of BPH adenoma more
fragile than prostate capsule
Adenoma can be heated to cause
necrosis
Capsule protected by better blood flow
Tissue necrosis, nerve
damage/destruction lead to improved
voiding symptoms

BLADDER
PROSTATE
URETHRA
Anatomy of BPH
Normal BPH
Hypertrophied
detrusor muscle
Obstructed
urinary flow
Roehrborn CG, McConnell JD. In: Walsh PC et al, eds. Campbell’s Urology. 8th ed. Philadelphia, Pa: Saunders; 2002:1297-1336.
2002:1297 1336.

Radio Frequency Generator
•Monitors temperature of
urethra and prostate 50 times
per second with Precision
Reassurance Technology
•Computerized graphics allow
physician to view treatment in
real time

Cartridge and Needle Deployment
Disposable Cartridge and
Reusable Handle
Dual Deployment of
Needles and Shields

Schematic of TUNA Procedure
Creation of a Lesion
Completed Procedure
with 8 Lesions

•
•
Transurethral Microwave Therapy
Microwave energy
causes tissue
necrosis
Cooling channels in
catheter cool urethra

•
•
•
Interstitial Laser Therapy
Lesions created
throughout prostate
Laser fiber alignment
critical
Median lobe can be
treated

Interstitial Laser Coagulation

•
•
•
•
Anesthesia Options
Local (lidocaine
Oral narcotics
Prostate block
I.V. sedation
jelly)

Treatment Results After Thermotherapy
•
•
•
•
Most patients see improvement in
symptoms
Results not as consistent as TURP
Bladder function important
Long term results of TUNA, TUMT and
ILT are similar

TURP (Rotor Rooter)

The TURP

Laser Prostatectomy
1. PVP
2. Thulium
3. Diode

ABSORPTION vs.
AVELENGTH
120W 70W
200W
980nm is 2300 times more absorbed in H 2 O than 532nm
532nm is 74 times more absorbed in H b O 2 than 980nm

KTP
532 nm
0.8 mm
Optical Penetration Depth
Diode
830 nm
5 mm
Diode 980nm RevoLix
Nd:YAG
1064 nm
10 mm
Ho:YAG
2100 nm
0.4 mm
CO2 10 μm
0.02 mm
Tissue

PVP Laser Prostatectomy
•
•
•
Vaporizes tissue
Minimal bleeding
No catheter post-op

Pre Op Immediate Post Op
3 Months Post Op

PVP Laser Removes Tissue
•
•
•
•
Opens bladder neck
Cavity similar to TURP
Improvement in symptoms similar to
TURP
Less impotence than TURP, other
morbidity similar

30
25
20
15
10
5
0
Mean Peak Flow Rate (ml/s)
7.8
Green Light PVP
27.3
26.2
23.3 23.4
pre-op 1 year 2 years 3 years 5 years
Malek et al., Mayo Clinic, Durability Study

160
140
120
100
80
60
40
20
0
Post Void Residual (ml.)
154
Green Light PVP
44 38
51
21
26
Pre-op 3 mos 6 mos 12 mos 24 mos 36 mos
Malek et al., Mayo Clinic, Durability Study

25.0
20.0
15.0
10.0
5.0
0.0
22.0
Green Light PVP
AUA Semptom Skoru
3.9 3.6 3.6
2.9
pre-op 1 year 2 years 3 years 5 years
Malek et al., Mayo Clinic, Durability Study