2. Understanding the prostate
Walnut-shaped gland that forms part of the
male reproductive system
Surrounds the urethra - the tube that
carries urine from the bladder out of the
body
3. Understanding the prostate
Secretes semen which
carries sperm
Duringorgasm, prostate
muscles contract and
propel ejaculate out of
the penis
4. BPH
The size of prostate enlarged microscopically since the
age of 40.Half of all men over the age of 60 will develop
an enlarged prostate
By the time men reach their 70’s and 80’s, 80% will
experience urinary symptoms
But only 25% of men aged 80 will be receiving BPH
treatment
5. What is Benign Prostatic
Hyperplasia?
Peripheral zone
Transition zone
Urethra
7. What causes BPH?
BPH is part of the natural
aging process, like getting
gray hair or wearing glasses
BPH cannot be prevented
BPH can be treated
8. What’s LUTS?
Voiding (obstructive) Storage (irritative or
symptoms filling) symptoms
• Hesitancy • Urgency
• Weak stream • Frequency
• Straining to pass urine • Nocturia
• Prolonged micturition • Urge incontinence
• Feeling of incomplete
bladder emptying
• Urinary retention
LUTS is not specific to BPH – not everyone with
LUTS has BPH and not everyone with BPH has LUTS
Blaivas JG. Urol Clin North Am 1985;12:215–24
9. Diagnosis of BPH
• Symptom assessment
– the International Prostate Symptom Score (IPSS) is recommended as it is used
worldwide
– IPSS is based on a survey and questionnaire developed by the American Urological
Association (AUA). It contains:
• seven questions about the severity of symptoms; total score 0–7 (mild), 8–19 (moderate),
20–35 (severe)
• eighth standalone question on QoL
• Digital rectal examination(DRE)
– inaccurate for size but can detect shape and consistency
• PV determination- ultrasonography
• Urodynamic analysis
– Qmax >15mL/second is usual in asymptomatic men from 25 to more than 60 years of
age
• Measurement of prostate-specific antigen (PSA)
– high correlation between PSA and PV, specifically TZV
– men with larger prostates have higher PSA levels 1
– PSA is a predictor of disease progression and screening tool for CaP
– as PSA values tend to increase with increasing PV and increasing age, PSA may
be used as a prognostic marker for BPH
10. Interfere with sexual life
Sexual Activity Decreases with
Average sex intercourse/activity/ month
9 8.5 n=12,815
Age and LUTS: MSAM-7 Survey
8 7.6 IPSS = 0
7 6.6 IPSS 1–7
5.7 5.7 IPSS 8–19
6
4.9 IPSS 20–35
5 4.6
4.0
4 3.7 3.5
2.6
3 1.7
2
1
0
50–59 years 60–69 years 70–79 years
Rosen et al. Eur Urol 2003 n=12815
11. When should BPH be treated?
BPH needs to be treated ONLY IF:
Symptoms are severe enough to bother
the patient and affect his quality of life
Complications related to BPH
12. Choosing the right treatment
Consider risks, benefits
and effectiveness of each
treatment
Consider the outcome and
lifestyle needs
14. “watchful waiting”
For mild symptoms. follow up1 to 2 times
yearly
Offer suggestions that help reduce
symptoms
Avoid caffeine and alcohol
Avoid decongestants and antihistamines
15. Medication
First line of defense against
bothersome urinary symptoms
Two major types:
α blockers - relax the smooth
muscle of prostate and provide a
larger urethral opening
(Hytrin,Doxaben, Harnalidge)
5 α reductase inhibitor -
Shrink the prostate gland
(Proscar, Avodart)
16. Medication
Benefits Disadvantages
Convenient Drug Interactions
No loss of work Must be taken every day
time
Manages the problem
Minimal risk instead of fixing it
17. Possible side effects of
medication
• Impotence
• Dizziness
• Headaches
• Fatigue
• Loss of sexual drive
18. α-Adrenergic Blockers: Rationale
• Prostate smooth muscle tone is mediated via
α1-adrenergic receptor
• Blockage of the receptor leads to improvement
of flow rate and LUTS1
• Central α-receptors and the effect of agents on
these receptors likely play an additional role
• Density of adrenergic receptors changes with
prostate size and age
• Three α1-adrenergic receptor subtypes
have been identified (A, B, D)
Schwinn DA. BJU Int. 2000;86(suppl 2):11-22.
22. α1-Adrenergic Blockers: Summary
• All currently available α1-blockers induce fast
improvement in LUTS and flow rate parameters
with similar efficacy
• They are all well tolerated; however, the adverse
event spectrum differs between the agents
– Terazosin and doxazosin induce more dizziness, fatigue,
and asthenia
– Tamsulosin induces more ejaculatory disturbances
• None of the α1-blockers alter urodynamic parameters,
prostate volume or serum PSA
• None have been shown to alter the natural history of
the disease or prevent AUR / Surgery
23. 5α-Reductase Inhibitor: Rationale
• Prostatic differentiation & growth depend on androgenic
stimulation
• Testosterone is converted to dihydrotestosterone (DHT)
within the prostatic stromal & basal cells facilitated by
5α-reductase enzyme
• 5α-reductase inhibitor: deprive the prostate of its
testosterone support
• 5α-reductase enzyme:
Type I: skin & liver
Type II: stromal & basal cells of prostate, seminal vesicle,
epididymis
Kirby RS et al. Br J Urol. 1992;70:65-72
Tammela TLJ et al. J Urol. 1993;149:342-344
24. Regulation of cell growth in the
prostate in BPH
Serum testosterone (T) Serum Dihydrotestosterone
(DHT)
T Prostate
5AR (1 and 2) DHT cell
Growth DHT-androgen
factors receptor complex
Cell death
Increased Unbalanced
Cell growth
25. 5α-reductase inhibition
Mode of action
OH OH
5 α-reductase type 1 and 2
O O
NADPH NADP H
Testosterone Dihydrotestosterone
Avodart (dutasteride) - Dual (type 1&2) 5ARI
Proscar(finasteride) - Only type 2 5ARI
26. Greater and more consistent suppression
of DHT observed with dutasteride
versus finasteride (n=399)
DHT (% change from baseline)
40 Treatment
withdrawn Placebo
20 Fin 5.0 mg
Dut 0.5 mg
0
-20
-40
-60 100% Dut patients
>70% 49% Fin patients
-80
>90% 85.4% Dut patients
-100 2.2% Fin patients
0 4 8 12 16 20 24 28 32 36 40
Time (weeks)
Richard V. Clark et al. J Clin Endocrinol Metab 89:2179-2184, 2004
Roehrborn et al (2003)
27. Comparison of adverse events:
Dutasteride vs. finasteride vs. placebo
(n=399)
Patients (%)
100
Placebo
Dutasteride 0.5 mg
80
Dutasteride 5.0 mg
Finasteride 5.0 mg
60
40
20
0
Any AE Drug-related Serious AE Withdrawal
AE due to AE
Richard V. Clark et al. J Clin Endocrinol Metab 89:2179-2184, 2004
28. Dutasteride 4-year studies
(2-year double-blind and 2-year open-label)
Randomised to double-blind phase
n=4325
Key inclusion criteria:
aged ≥ 50 years, diagnosis of BPH, PV ≥ 30 cc,
AUA-SI score ≥ 12, Qmax ≤ 15 mL/sec, PSA ≥ 1.5 ng/mL
Placebo Dutasteride
n=2158 n=2167
Entered open-label phase Entered open-label phase
on dutasteride n=1152 on dutasteride n=1188
P/D D/D
Roehrborn CG et al Urol 63:709-15,2004
29. Dutasteride therapy results in reductions
in total prostate volume from 1– 24
months that are sustained to 4 years
Placebo Dutasteride Open-label dutasteride after placebo
Mean change (%)
5 * * *† *‡
1.4
0.2
0
-0.6 -1.5
-2.1
-5
-5.2
-10
-15 -13.8
-20
-19.9
-21.7
-25 -23.6
-26.0
-30 -27.3
Treatment month 1 3 6 12 24 48
*p<0.001 for differences between treatment groups
†p<0.001 for change from Month 24 to Month 48
‡p=0.07 for change from Month 24 to Month 48
Roehrborn CG et al Urol 63:709-15,2004; Debruyne F et al, Euro Urol 2004;46: 488-495
30. Dutasteride therapy results in symptom
improvements from 6 months, with continuing
improvements over 4 years (completers)
Change in AUA-SI (units)
0 Double-blind Open-label
-1 P/D (n=1152)
-2 D/D (n=1188)
*
-3
-2.7
-4
-5
*†
-5.0 -5.6
-6
-6.5
-7
0 3 6
9 12 15 18 21 24 27 30 33 36 39 42 45 48
*p<0.001 between treatment groups
Treatment month
†p<0.001 for differences within treatment groups from Month 24
Roehrborn CG et al Urol 63:709-15,2004; Debruyne F et al, Euro Urol 2004;46: 488-495
31. Dutasteride therapy results in improvements
in urinary flow from 1 month, with
continuing improvements over 4 years
Mean change P/D (n=1152)
(mL/sec)
D/D (n=1188)
3.0 †
* × 2.7
2.5 2.2
2.0 ¤
1.9
1.5
1.0
0.5
0.6
0.0
0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48
Treatment month
*p<0.001 between treatment groups
†p=0.042 between treatment groups
¤p<0.001 vs. Month 24
×p=0.007 vs. Month 24
Roehrborn CG et al Urol 63:709-15,2004; Debruyne F et al, Euro Urol 2004;46: 488-495
32. Acute urinary retention
Kaplan-Meier estimates: time to first event
Patients (%)
7 Double-blind Open-label 6.7%
6
5 P/D
4 D/D
57
3 3.3%
%
2
1
0
0 6 12 18 24 30 36 42 48
Treatment month
Roehrborn CG et al Urol 63:709-15,2004; M.Emberton et al. 2004 EAU Abstract
33. BPH-related surgery
Kaplan-Meier estimates: time to first event
Patients (%)
7 Double-blind Open-label
6
5.6%
5 P/D
4 D/D
48
3 3.3%
%
2
1
0
0 6 12 18 24 30 36 42 48
Treatment month
Roehrborn CG et al Urol 63:709-15,2004; M.Emberton et al. 2004 EAU Abstract
34. PSA is reduced in a predictable
manner preserving its prostate cancer
screening utility
Double-blind Open-label
20
Mean (+/- SE) % Change
10
0
-10
-20
-30
-40
-50
-60 -57.2
0 6 12 18 24 30 36 42 48
Treatment Month
Placebo n=1152
Dutasteride
n=1188
Data on File GlaxoSmithKline
35. Long-term change in prostate volume
Indirect comparison of dutasteride,
finasteride and a-blockers
% Change in prostate
volume from baseline Dutasteride
30 Finasteride
α-blockers
20
10
0
-10
-20
-30 2 yr 4 yr PLESS MTOPS 6 yr MTOPS
DB OL 4 yr 4 yr OL Dox
4 yr
McConnell et al. (1998); McConnell et al. (2003); Roehrborn et al. (2002); Lowe et al. (2003)
36. Symptom improvement
Indirect comparison of a-blockers,
finasteride and dutasteride
Mean AUA-SI score Dutasteride
reduction from baseline Finasteride
9 α-blockers
8
7
6
5
4
3
2
1
0
1y 2y 4y AUA PLESS MTOPS 5y Tam Tam Tam Alf Tera Dox Dox
DB DB OL 1y 4y 4y OL label label 5y 1y AUA AUA 4y
13 wk 13 wk OL OL 1y 1 y MTOPS
study 1 study 2
McConnell et al. (1998); McConnell et al. (2003); Roehrborn et al. (2002); AUA (2003)
38. Rationale for Combination Therapy
Alpha blockers relax the smooth muscle of bladder neck
and prostatic capsule/adenoma, thereby improving
symptoms and flow rates, relieving obstruction
5 ARIs reduce the action of androgens in the prostate,
inducing apoptosis, atrophy, and, by shrinking the
prostate improve symptoms, relieve obstruction and
prevent AUR & prostate surgery
5ARIs α1-adrenergic
? blockers
Arrest disease progression Rapidly relieve symptoms
40. Change in AUA Symptom Score
at Year 4
Placebo 4.0
Doxazosin 6.0 (p<0.001)
Finasteride 5.0 (p<0.047)
Combination 7.0 (p<0.001)
2 4 6 8 10
Median point decrease from baseline
Median baseline AUA SS = 17.0
41. Change in Qmax at Year 4
Placebo 1.4
Doxazosin 2.5 (p<0.001)
Finasteride 2.2 (p<0.047)
Combination 3.7 (p<0.001)
1 2 3 4 5
Median point decrease from baseline
Median baseline Qmax = 10.6
42. Conclusions
Single arm therapy with alpha blocker
Improve symptoms and prevent symptom progression
Does not alter natural history or cross over to invasive therapy
Single arm therapy with 5 ARI
Treats symptoms only when LUTS associated with BPH (ie
enlargement or high PSA)
Alters natural history in pts at risk (large gland, high PSA)
Combination (doxazosin+finasteride) therapy is the most
effective form of treatment for LUTS and BPH
Improve symptoms and flow rate
Prevent AUR and/or surgery
Alter the natural history of the disease
43. Symptom Management After
Reducing Therapy: SMART–1
SMART–1 was designed to examine
short-term dutasteride and a1-blocker
combination therapy, followed by
dutasteride monotherapy
Entry criteria:
IPSS ≥ 12
PV ≥ 30 cc, estimated by DRE
PSA 1.5 – 10.0 ng/ml
Barkin et al (2002)
44. SMART-1: study design
DT24 + D12
DT36
dutasteride 0.5mg
Combination + placebo
Placebo
Placebo dutasteride 0.5mg (tamsulosin)
run-in + tamsulosin 0.4mg
once daily
Combination
4 weeks 24 weeks 12 weeks 1 week
Single Single Double blind Single
blind blind blind
Wk 30 Wk 36
Barkin et al (2002)
45. SMART-1: primary endpoint question
at week 30 by baseline IPSS
Moderate Severe
(baseline IPSS <20) (baseline IPSS ≥20)
(n=220) (n=82)
100 93%
84% 86%
80
Patients (%)
57.5%
60
40
Severe pts need longer AB treatment
20
0
DT36 DT24 + D12 DT36 DT24 + D12
% patients better/same
Barkin et al (2002)
46. 5 α Reductase Inhibitors
成份 Finasteride Dutasteride*
Compared to
PROWESS1 PLESS2 MTOPS3 2yrs4 4yrs5,6,7
Baseline
Duration (yr) 2 4 4 2 4
Total Prostate Volume -15.3% -18% -19% -25.7% -27.3%
Symptoms -2.1 -3.3 -5.6 -4.5 -6.5
Urinary Flow Rate 1.5 1.9 3.2 2.2 2.7
Continue
Risk of AUR -57% -57% -68% -57% Reduction
Continue
Risk of BPH Surgery -40% -55% -64% -48% Reduction
Note: Not from a comparative trial, all result abstracted from treatment group.
PROWESS=Proscar Worldwide Efficacy and Safety Study; PLESS=Proscar Long-term Efficacy and Safety Study;
MTOPS=Medical Therapy of Prostatic Symptoms
*: Avodart Phase III trial 為在 2 年的 double blind 後再延長 2 年至 4 年的 open-label study
References:
1. Marberger MJ. Urol.51:677-86,1998 。 2. McConnell JD et al. N Engl J Med 338(9):577-63,1998 。 3. McConnell JD et
al. N Engl J Med 349(25):2387-98,2003 。 4. Roehrborn CG et al.Urol.60:434-41,2002 。 5. T.Tammela et al. 2004 EAU
Abstract 。 6. F.Debruyne et al. 2004 EAU Abstract 。 7.M.Emberton et al. 2004 EAU Abstract 。
47. Conclusions
In MTOPS study, finasteride afforded long-term reduction
in risk of AUR on surgery when combined with alpha 1-
blocker doxazosin
In SMART-1 study, dutasteride can be used in
combination with tamsulosin to achieve fast symptom
relief that is maintained with alpha 1- blocker is removed
after 6 months
48. Medical Therapy Algorithm
Patient
IPSS IPSS
≤7 >7
No or Moderate to
little severe
bother bother
Prostate Prostate Prostate Prostate
small large small large
PSA low PSA high PSA low PSA high
No α-
Preventive therapy 5α-Reductase
Treatment Adrenergic
5α-Reductase Inhibitor Inhibitor
Blocker
Combination Rx
IPSS <19 IPSS >19
(Moderate) (Severe)
Short term Long term
53. TURP
(transurethral resection of the prostate)
“Gold Standard” of care for BPH
Uses an electrical “knife” to surgically cut
and remove excess prostate tissue
Effective in relieving symptoms and
restoring urine flow
55. The “gold standard”- TURP
Benefits Disadvantages
Widely available Greater risk of side
effects and complications
Effective
1-4 days hospital stay
Long lasting
1-3 days catheter
4-6 week recovery
56. Complication of TURP
• Immediate complication
bleeding
capsular perforation with fluid extravasation
TUR syndrome
• Late complication
urethral stricture
bladder neck contracture (BNC)
retrograde ejaculation
impotence (5-10%)
incontinence (0.1%)
57. Open Simple Prostatectomy
• “too large prostate” -- >100 gm
• Combined with bladder diverticulum or
vesical stone surgery
• Suprapubic or retropubic method
58. Minimally invasive therapy
• During the last decade, numerous amounts of
minimally invasive therapy modalities have
been developed to challenge the traditional
surgery of TURP
• The aim of these therapies is to achieve
results similar to TURP but with minimal
anesthesia, complication, risk and hospital
stay.
59. Minimally invasive therapy for
BPH
• transurethral balloon dilatation of the prostate
(TUBDP)
• transurethral incision of the prostate (TUI)
• intraprostatic stent
• transurethral microwave thermotherapy (TUMT)
• transurethral needle ablation of the prostate (TUNA)
• transurethral electrovaporization of the prostate
(TUVP)
• photoselective vaporization of the prostate (PVP),
• Cryotherapy
• Transurethral ethanol ablation of the prostate
(TEAP),
60. Minimally invasive therapy for
BPH
• transurethral laser-induced prostatectomy
(TULIP)
• visual laser ablation of the prostate (VLAP)
• contact laser prostatectomy (CLP)
• interstitial laser coagulation of the prostate (ILC)
• holmium:YAG laser resection of the prostate
(HoLRP)
• holmium:YAG laser enucleation of the prostate
(HoLEP)
• high-intensity focused ultrasound (HIFU)
coagulation
• botulinum toxin-A injection of the prostate
61. HoLEP Vs. TURP
• IPSS & urodynamic findings: no statistically significant
differences
• Operation time:
HoLEP 74 +/- 19.5 vs. TURP 57 +/- 15 mins (p <0.05)
• Catheterization time:
31 +/- 13 vs 57.78 +/- 17.5 hours (p <0.001)
• Hospital stay:
59 +/- 19.9 vs 85.8 +/- 18.9 hours (p <0.001)
• Urge incontinence: more common in the HoLEP group
• The overall complication rate was comparable in the 2
groups
Journal of Urology. 172(5, Part 1 of 2):1926-1929, November 2004
62. TURP vs HIGH POWER (80 W) POTASSIUM TITANYL
PHOSPHATE (KTP) LASER VAPORIZATION
• Hemostasis: standardized ablation volume of 16 cm 3
tissue (23.3 vs 2.1 ml per minute, p <0.0001).
• Tissue ablation: more rapid in the resection group
(100 vs 20 seconds, p <0.001).
• Histological examinations: larger coagulation zones for
the KTP group compared to conventional tissue resection
(0.9 vs 0.6 mm, p <0.01).
• 80 W KTP laser vaporization: bloodless ablative
procedure, but more time-consuming
Journal of Urology. 171(6, Part 1 of 2):2502-2504, June 2004
63. How does PVP work?
Uses a very high powered green laser and
a thin, flexible fiber
Fiber is inserted into
the urethra through a
cystoscope
64. How does PVP work?
Quickly
and precisely vaporizes and
removes the enlarged prostate tissue
The green laser energy is hemostatic, so
there is almost no bleeding
65. Enlarged Prostate After GreenLight PVP
Urethra is obstructed Urethra is open
Urine flow blocked Normal urine flow is
restored
66. Summary
• Minimally invasive therapies for the treatment of BPH
has the advantages such as less blood loss, less
occurrence of hyponatremia, quicker recovery, and
reduced risk of urethral stricture.
• However, it also has the disadvantages such as long-
lasting bladder irritation owing to higher temperature
during therapy and possible longer catheterization
period due to swelling of the prostate.
• It is still too early to make a definitive conclusion
concerning the future role of these minimally invasive
therapies for the treatment of BPH.
Hinweis der Redaktion
LUTS can arise from a variety of causes, for example as a consequence of prolonged urinary obstruction due to BPH. LUTS are categorised as being obstructive (voiding) or irritative (storage) symptoms. Obstructive symptoms include hesitancy, weak stream, straining to pass urine, prolonged micturition, feeling of incomplete bladder emptying, and urinary retention. Irritative symptoms include urgency, frequency, nocturia, and urge incontinence. LUTS may also be due to inflammatory or infectious processes.
The initial evaluation can be done either by a Primary Care Practitioner (PCP) or by a urologist. If the initial evaluation suggests a diagnosis of BPH, the physician can proceed to develop an appropriate treatment plan. The physical examination should include specific attention to the presence or absence of a distended bladder, urethral discharge, genital abnormalities, and neurologic abnormalities that can affect voiding. A digital rectal examination (DRE) is considered an important part of the physical examination of any patient complaining of symptoms of prostatism. This examination is conducted with a well-lubricated, gloved index finger, which is used to palpate the prostate gland and the surrounding tissues through the wall of the rectum. Because of the prevalence of prostatic disease in older men, many physicians conduct DREs as part of the routine annual physical examination of any man over the age of 50 years. The size, consistency, shape, and symmetry of the prostate gland can be felt through the rectal wall during a DRE. Several questionnaires are used to assess the severity of symptoms and their impact on a patient’s QoL. American Urology Association-Symptom Score (AUA-SI) or International Prostate Symptom Score (IPSS), QoL score and BPH-II. In men with symptoms of BPH, a urine sample should be examined for signs of a urinary tract infection or haematuria, both of which suggest a non-BPH cause for the LUTS. Both urinary tract infections and bladder cancer can produce symptoms similar to those produced by BPH.
Relaxation of these muscle bundles lessens the resistance to outflow during urination.α
Medications address the desire we all have to find a “cure” to fix the problem. We all like a “quick and easy” solution. They can, however, become less effective over time. Studies have shown that people tend to become less careful about following directions regarding the dose and/or frequency of taking their medication.
Relaxation of these muscle bundles lessens the resistance to outflow during urination.
[Dr. McVary, transcript page 26] Prostate smooth muscle tone is mediated via 1 -adrenergic receptors. Increased tone of the prostate smooth muscle leads to BOO and a reduction in urinary flow rate. Blockage of the 1 -adrenergic receptor relaxes prostate smooth muscle and relieves BOO. 1 Studies indicate that, overall, 1 -adrenergic receptor expression doubles with age (<55 y vs 65 y). 2 To date, three 1 -adrenergic receptor subtypes have been identified: 1A , 1B , and 1D . 1 Schwinn DA. Novel role for 1 -adrenergic receptor subtypes in lower urinary tract symptoms. BJU Int. 2000;86(suppl 2):11-22. Rudner XL, Berkowitz DE, Booth JV, et al. Subtype specific regulation of human vascular 1 -adrenergic receptors by vessel bed and age. Circulation. 1999;100:2336-2343.
Alpha-1 Blockers: Conclusions In conclusion, all alpha blockers currently available induce fast improvement in LUTS and flow rate parameters, with similar efficacy across all alpha blockers These agents are all well tolerated; however, the adverse event spectrum differs between the agents with Terazosin and doxazosin inducing more dizziness, fatigue and asthenia Tamsulosin inducing more ejaculatory disturbances Nevertheless, none of the alpha blockers alter prostate volume or serum PSA, and none have been shown to significantly change the rate of AUR/surgery
Dutasteride was associated with a significant reduction in the risk of AUR (57%) compared to placebo during the first 2 years of the studies Between 2-4 years, when all patients are receiving dutasteride, AUR occurred at a lower rate in the switchers than observed for these patients in years 0-2, and at a rate consistent with that seen in dutasteride-treated patients between 0-2 years.
Dutasteride was associated with a significant reduction in the risk of BPH-related surgery (48%) compared to placebo during the first 2 years of the studies Between 2-4 years, when all patients are receiving dutasteride BPH-related surgery occurred in a small percentage of men, at slightly lower rates than seen in dutasteride-treated men between 0-2 years
As this is not comparator data patient populations from the various studies may differ. dutasteride data for 1, 2 and 4 years is shown in yellow. Continuing improvement in symptoms over the 4 years is seen. Finasteride data for 1, 4 and 5 years is shown red, including that from PLESS & MTOPS. Alpha blocker data for 13 weeks to 5 years in shown in green. dutasteride symptom improvement at 4 years is comparable to that seen for alpha blockers.
SMART-1 was a randomised, blinded, parallel group, multi-centre pilot study in male subjects with symptomatic BPH. Eligible subjects were entered into a four week single-blind placebo run-in phase prior to randomisation to Avodart 0.5mg plus tamsulosin 0.4mg combination therapy for 24 weeks. At the 24-week time-point, approximately half of the subjects had tamsulosin removed from their treatment regimen in a double-blinded manner. These subjects received Avodart monotherapy for a further 12 weeks (to week 36). The other group of subjects continued to receive Avodart plus tamsulosin combination therapy for a further 12 weeks (to week 36).
Approx 1/10 patients responded that they were worse at week 30, after withdrawal of the alpha blocker at week 24. As could be expected those patients who responded that they were worse following withdrawal of the alpha blocker were likely to have a severe IPSS score at baseline.
No change requested.
Until recently, the only option we could offer patients for treatment of their symptoms was either an open abdominal surgical procedure, or a trans-urethral resection of the prostate.
[Dr. McVary, transcript page 24] Treatment options for BPH include watchful waiting, medical therapy, and various surgical procedures. 1-3 About 42% of patients treated with placebo or watchful waiting report symptomatic improvement compared with about 98% for open prostatectomy. 2 Symptom improvement with medical treatment is less than that with surgical procedures. The mean probability of symptomatic improvement is 74% with an -adrenergic blocker versus 98% with an open prostatectomy. 2 However, disadvantages of surgery include invasiveness, a period of recuperation and, in the case of open surgery, a comparatively prolonged hospitalization. 3 Watchful waiting is a strategy of management/monitoring in which patients receive no active treatment. 2 Phytotherapy involves the use of plant extracts for medicinal uses. 4 Today, -adrenergic blockers, which inhibit contraction of prostatic smooth muscle, are first-line treatment for LUTS/BPH. Another pharmacologic option is the 5ARI, finasteride, which lowers prostatic androgen levels and can result in some decrease in prostate size. Office-based procedures include transurethral microwave thermotherapy (TUMT) and transurethral needle ablation (TUNA). Transurethral resection of the prostate (TURP), the gold standard and most common active treatment, is the surgical removal of the prostate ’ s inner portion, using an endoscopic approach through the urethra. 2,3 Transurethral incision of the prostate (TUIP) is also an endoscopic surgical procedure. Patients with smaller prostates ( < 30 g) have an instrument inserted through the urethra to make one or two cuts in the prostate that reduce urethral constriction. 2,3 Open surgery (prostatectomy) is the surgical removal of the prostate via an incision in the lower abdomen. 2,3 Transurethral vaporization of the prostate (TUVP or TVP) applies electrical energy to electrosurgically vaporize the obstructive enlarged prostatic tissue. The laser is inserted under direct vision into the prostate and activated to destroy the surrounding tissue. 3 With visual laser ablation of the prostate (VLAP), a laser fiber is passed into the prostatic channel under telescopic guidance to destroy the obstructing portions of the prostate. Stents are wire devices shaped like small springs or coils, which are placed within the prostate channel to keep the channel open. 3 Chatelain C, Denis L, Foo JKT, et al. 5th International Consultation on BPH. Recommendations of the International Scientific Committee: Evaluation and treatment of lower urinary tract symptoms (LUTS) in older men. In: Chatelain C et al, eds. Benign Prostatic Hyperplasia . Plymouth, UK: Health Publication Ltd; 2001:519-534. McConnell JD, Barry MJ, Bruskewitz RC, et al. Benign Prostatic Hyperplasia: Diagnosis and Treatment . Clinical Practice Guideline, Number 8. AHCPR Publication No. 94-0582. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services. February 1994. Columbia University website. Therapies for the treatment of benign prostatic hyperplasia (BPH). Available at http://cpmcnet.columbia.edu/dept/urology/bphtherapy.html#translas. Accessed 8/23/01. Dreikorn K, Lowe I, Borkowski A, et al. Other medical therapies. In: Chatelain C et al, eds. Benign Prostatic Hyperplasia . Plymouth, UK: Health Publication Ltd; 2001;479-511.