Summary on Benign Prostatic Hyperplasia and BPH

1. 1
BPHBPH
Edmond Wong

2. 2
Embryology of the prostate
• Prostate develop from week 10-16
• SRY gene product stimulated medullary sex cord to develop into
pre-sertoli cell
• These cells secret Mullerian-inhibiting substance (MIS)
• MIS stimulate Leydig cell to produce testosterone
• Induce development of the Wolffian duct (SV, epididymis, vas
deferrence, ejaculatory duct, central zone)
• Rest of the prostate develop from 5 pair of epithelial buds which
branch out from the posterior aspect of the urogenital sinus
• Invade into the mesenchyme to stimulate development of the
prostatic stroma (upper pair) and transitional zone (lower pair)
• Stromal- epithelial interaction is important thru production of DHT by
stromal cell acting on the androgen receptor of epithelial cells
(paracrine action)

3. 3

4. 4
What are the blood supply to the
prostate?
• Arterial blood supply:
– Inferior vesical artery  Prostatic artery
• Urethral: BN and urethra
– Flock’s artery (1 & 11 oc)
– Badenock’s artery (5 & 7 oc)
• Capsular group: Run with the cavernosal nerves
• Venous drainage:
– Periprostatic venous plexus
– Deep dorsal vein of the peni
– Mumerous vesical vein
• Drain into the internal iliac vein
• LN: Obturator & internal Iliac LN

5. 5
McNeal’s zonal anatomy
• Transitional zone (10%): BPH
• Central zone (25%)
• Peripheral zone (65%): Ca Prostate
• Anterior fibromuscular stroma
• Peri-urethral zone

6. 6

7. 7

8. 8
What are the necessary aetiological riskWhat are the necessary aetiological risk
factors for BPH formation?factors for BPH formation?
• Aetiology of BPH is still not well known
• BPH : a process of increased proliferation (early phase) but
more importantly decrease in apoptosis (established phase)
• “Reawakening” of the inductive effect of the prostate stromal cell
on the epithelial cell (like in fetal development)
• Aetiological risk factors :
1. Age
2. Androgens (a permissive role only)
3. Race
4. Diet
5. Genetics (role again unclear) – 50% of men undergoing
prostatectomy before 60 could be attributed to have some
genetic factors
6. Growth factors (basic fibroblastic GF, insulin-like GF, etc)

9. 9
Relationship between metabolicRelationship between metabolic
syndrome and BPHsyndrome and BPH
• Metabolic syndrome at least 3 out of the 5 following
points
– HT / Abdominal obese / Hyperglycemia /
Hypertriglyceridermia / Hypo-HDL cholersterol
• MS induced BPH
– Chronic inflammation via interleukin and CRP
– Increased insulin like growth factor
– Increased cholesterol > hormonal change
– Autonomic hypersensitivity by neurodegeneration of
parasympathetic neuron
• Weight reduction, statin, cholesterol absorption
inhibition drugs > may reduce prostate growth

10. 10
What are Cunha’s
experiments?
What are McNeal’s
hypothesis?

11. 11
• Cunha
– Prostatic epithelial development and
differentiation is indirectly controlled by
androgens via androgen dependent mediators
of stromal in origin
• McNeal
– BPH is the result of a reawakening of
embryonic processes in stroma which induces
epithelial cell development via growth factors
• (Inhibitory ones like TGF-beta)

12. 12
Role of hormone in BPH
• Testosterone can bind directly to
the AR, or converted to DHT by
5AR
• 2 isoform:
– Type 1: extraprostatic (skin, live)
– Type 2: Prostatic (nuclear
membrane of stromal cell, but not
in epithelial cell)
• Testosterone diffuse into cell:
– Epithelial cell : bind to AR & induce
growth factor
– Stromal cell: Majority convert to
DHT by Type 2 5AR  bind to
androgen receptor or diffuse into
nearby epithelial cell (paracrine
action)
• Complex bind to specific binding
site of nucleus  induce
transcription of androgen-
dependent gene
• Protein synthesis and development
of BPH

13. 13
What is the pathology of
BPH?
• Hyperplastic process
• Earliest sign : micronodule formation in
transitional zone – lateral lobes (mixture of
stromal cell and epithelial component) and in
periurethral region – median lobe within the
smooth muscle collar of the preprostatic
sphincter (mainly connective tissue)
• Further coalescence and growth of micronodule
become macronodule

14. 14
Pathophysiology of BOO
• BOO cause thickening of bladder wall
• High intra-renal pressure  hydronephrosis
• Impair renal function & even renal failure
• Microscopic:
– Smooth muscle cell enlarged
– Increase in connective tissue (collagen and elastin) btw SM
bundles
– Lead to poor compliance
• BOO also cause bladder overactivity
– Prolong increase intravesicle pressure during voiding
– Ischemia of bladder wall
– Damage to neurons within the bladder (denervation)

15. 15
Some clinical definition
• LUTS: Lower urinary tract symptom:
– Non-specific terms for symptom which may be attributable to
lower urinary tract dysfunction
– Storage LUTS (Frequency, Urgency, Nocturia)
– Voiding LUTS (Hesitancy, Straining, Slow stream, intermittency,
terminal dribbling, sense of incomplete voiding)
• BOO: Bladder outflow obstruction
– Urodyanmical diagnosis of an obstruction to passage of urine
• BPE: Benign prostate enlargement:
– Clinical finding of an enlarged prostate
• BPH: Benign prostatic hyperplasia:
– Histological basis of BPE leading to BOO that result in LUTS
• BPO: Benign prostatic obstruction:
– BOO cause by BPE

16. 16
How would described the
relationship btw BOO and LUTS
• What are Hald’s rings?

17. 17
60-yr-old man complaining of LUTS
•Evaluation
– Look for extraprostatic causes of LUTS
– Identify risk factors for progression that may affect treatment
– Identify comordities that may affect treatment
•History
– Age
– Storage and emptying symptoms: Duration, extent , troublesome
– Life style: fluid intake , adjustment has been made
– Incontinence : Type , frequency
– Hematuria, dysuria, bladder pain
– Loin pain , passage of stone
– Drug: Trail of medication , sympathomimetic , anticholinergic
– PMH: Urethral injury/ instrumentation, pelvic surgery, neurological disorder
•Examination
– Ballotable kidneys, palpable bladder, DRE and anal tone
– Signs of renal failure (uraemia, fluid overload)
– Neurological (gait and LL)

18. 18
• Investigations
– PSA
– Serum creatinine
– Urinalysis
– Frequency- volume chart (assess fluid intake)
– Uroflowmetry + PVR
• Only indicated when bother is mod to severe OR invasive treatment
considered (in AUA)
• <10ml/s - 90%obstructed, 10-15ml/s - 60% obstructed, >15ml/s –
30%
– IPSS scores & QOL scores
• Assess severity (guide treatment)
• Risk factor for progression
• Optional
– Upper tract imaging (USG kidney)
– TRUS prostate
– UDS
– Cystoscopy + Cytology

19. 19
Ask specifically
• Bedwetting: high pressure chronic
retention
• Marked frequency + urgency with bladder
Pain  CIS
• Macroscopic hematuria  vascular
prostate or Ca Bladder
• Back pain or neurological symptom

20. 20
Differential Diagnosis of LUTS
• Prostate1
– Obstruction (BPH, BPE, BOO) (30%)
• Bladder1
– Detrusor overactivity (50%)
– Impaired detrusor contractility (30%)
– Sensory urgency
– Sphincteric incontinence
– Polyuria/nocturnal polyuria
• Medications2
– Antihistamines
– Antidepressants
1. Chaikin DC, Blaivas JG. Curr Opin Urol. 2001;11:395-398. 2. Su L et al. J Clin Epidemiol. 1996;49:483-487.

21. 21
When will you consider the
following investigation
• Renal USG:
– Loin pain / mass
– Hematuria
– Presence of renal
insufficiency (AUA)
• Risk of hydronephrosis
<1% if normal RFT
• Cystoscopy + Cytology:
– Hematuria (CIS)
– Equivocal flow
– Previous uro surgery (AUA)
• TRUS +/- Bx
– Abnormal DRE
– Raised PSA (age adj or >
4)
– Surgical txn planning (open
Millin prostatectomy , Laser
surgery) for sizing
– Consideration of 5AR-I txn
• Urodynamic:
– Equivocal Flow rate : VV <
150ml , Qmax > 10ml/s
– Age < 50 or >80
– Previous unsuccessful txn
of BPH
– Neurological hx of sign

22. 22
Why Renal function ?
• Because renal insufficiency associated with
increased risk of postop morbidity (25 vs
17%) in the Mebust study
• Although the incidence of renal insufficiency
among patients with LUTS ~ 10%, there is no
reliable way to single out these patients
based on symptoms or clinical evaluation
alone, and thus a serum creatinine is
necessary

23. 23
How would you instructed the pt for
FR + RU
• Good URF: VV > 150ml
• Attend for 2-3hour
• Drink 500-1000 ml fluid
• Wait for comfortably full bladder
• When pass urine into machine:
– Avoid compressing penis (squeeze artefact)
– Don’t wander around the funnel (abn recording)
– Aim pass at least 150ml
• Repeat if < 150ml , if the flow representative

24. 24
How many types of
uroflowmetry machines are
you aware of?
What are the normal values of a
60-yr-old man ?

25. 25
• Machine mechanisms
1. Rotating disk
2. Weight transducer
3. Dipstick capacitance

26. 26
NORMAL VALUES FOR UROFLOWMETRY
Gender Age (years)
Flow rate
(ml/s)
Males <40 >21
40-60 >18
>60 >13
Females <50 >25
>50 >18
( Abrams and Torrens, 1979 )

27. 27
What do you look in FR+RU?
• Void volume: >150 ml (adequate)
• Overdistension: > 500ml
• Maximum Flow: Qmax
– Risk of BOO in UD in relation to Qmax:
• >15ml/s (30%), 10-15ml/s (60%) < 10ml/s (90%)
– < 12ml/s  3x risk of progression [Jacobsen
1997]

28. 28
What do you look in FR+RU?
• Overall pattern:
– Box-like (plateau curve) : Stricture
– Hyperflow : OAB
– Prolonged time to Qmax: BPH
– Intermittent burst: DSD
• Residual volume: RU
– Vary considerably
– Cannot symptomatic outcome after TURP
– May be safe not to operated on RU< 350 [Wasson VA
study NEJM1995]

29. 29
Why is BOO so important ?
• It underpins the rationale behind disobstruction
operation (TURP) in men with BPH
• 2 component:
– Dynamic :
• Alfa1- adrenoceptor mediate SM contraction
• 40% of area density
– Static: mediate by volume effect of BPE
• Men with BOO: 90% symptomatic improvement
after TURP
• Men without BOO: 60% symptomatic
improvement after TURP
• Abrahms JU 1979

30. 30
How can we tell if patient has
BOO?
• ICS normogram: Categories patient as
obstructed, equivocal or unobstructed
• Abram-Griffith number (BOOI): Single
numerical value:
– Pdet@Qmax – 2x Qmax = AG number
(BOOI)
– > 40  obstructive
– 20-40  equivocal
– < 20  unobstructed

31. 31
ICS nomogram

32. 32
What are the different instrument
for measurement of LUTS in men?
• DAN (Danish Prostate Symptom Score)
• Bristol Male LUTS
• AUA
• IPSS
– Derived from AUA + 1 more QOL question
– Most commonly used
– Valid , Reliable and reproducible

33. 33
What are the domains asked
in the IPSS / AUA-SS?
?Mild/Mod/Severe IPSS

34. 34
IPSSIPSS
• 7 Question + 1 QOL
• How often do you experience:
– Voiding: Straining , intermittency, slow stream, sense of incomplete
voiding
– Storage: Nocturia (times), Frequency (<2 hr) , Urgency
• Frequency:
– not at all 0
– <1/5 : 1
– <1/2 2
– ½ : 3
– > ½ : 4
– all the time : 5 (except nocturia)
• 0-7 mild; 8-19 moderate, 20-35 severe
• QOL: 0:delighted > 6:terrible
• Reliable, reproducible and valid

35. 35

36. 36

37. 37
How many points of IPSS drop
is perceived by patient to be a
‘significant’ improvement ?
?Any factors affecting this

38. 38
Barry et al J Urol 1995
• A 3-point absolute drop in IPSS is
required for the patient to perceive as
improvement
• The required drop in score is greater in
those with higher baseline IPSS

39. 39
Any drawbacks of IPSS?
• Drawbacks
– Does not make a diagnosis, just a symptom
score
– Not prostate / BPH specific – females /
patients with CPPS can have an IPSS score

40. 40
Is there a relationship between
symptoms and other more
objective measures such as
prostate volume or flow rate?

41. 41

42. 42

43. 43
LUTS: Q to answer
• How common is BPH ? Histology , clinical
• Will I progress ? Natural history
• What are the risk factor of progression?
• Management:
– Watchful waiting
– Life style modification
– Medication: AARB, 5ARI, Combination
– Phytotherapy
– Surgery
• TURP
• Electrosurgical: TURVP , TURis
• Laser: PVP, HoLAP, HoLEP, HoLIP
• Ablation: TUMT, TUNA
• Open surgery: open retropubic, open transvesicle

44. 44
How common is BPH?

45. 45
Histology
• Histologically BPH is present
– ~25% in 50 years of age
– ~70% in 70 years of age
– ~90% in 80 years of age
– No histological BPH found before 30
Berry 1984 Autopsy studies
(Berry SJ, Coffey DS, Walsch P: The development of human benign
prostatic hyperplasia with age. J Urol 1984; 132; 474-479.)

46. 46
Clinical LUTS
• Clinically LUTS suggestive of BPH is present
– ~10% in 40s
– ~25% in 50s
– ~40% in 60s
– ~40% in 70s
– Overall 25% in 40-79
– Garraway Lancet 1991 (Stirling study)
Garraway WM, Collins GN, Lee RJ. High prevalence of benign prostatic
hypertrophy in the community. Lancet. 1991 Aug 24;338(8765):469–
471.

47. 47
Clinical LUTS
• According to OCS: Moderate to severe
urinary symptom in
– 40-49yo 13%
– 70yo 30%

48. 48
What is the natural history
of BPH?
Will I progress?

49. 49
What will happen if I opt for
WW?
• Ball study BJU1981:
– 100men on WW for 5yr
– 25% get better, 30% get worse, 40% same
– 2% AUR, 10% require surgery
– Most patients have stable symptoms
• Wasson VA study on WW vs TURP NEJM 1995:
– Pt on WW: 25% TURP, 30% get worse , 40% get
better

50. 50
Can you briefly tell me about
the Olmstead County Study?

51. 51
• Longitudinal community-based study in
Olmsted County in US where a group of
men with LUTS (n=2115) were observed
over a long period of time without
intervention from the observers
• (Good for looking at natural history of BPH
– better than looking at the placebo arm of
studies like MTOPS)

52. 52
• Olmsted County Study
– Mean decline in Qmx 0.2ml/s/yr (2%)
• Rate of decline faster with increasing age, lower
baseline Qmx, bigger prostates and higher SS
– Mean increase in SS 0.18/yr (0.2)
• Rate of increase faster with increasing age
– Prostate volume increase 2cm3/ yr
• Rate of growth faster with bigger prostates

53. 53
• Olmstead County Study (Jacobsen)
– AUR occurrence : 7 / 1000 person-year on average
– Cumulative incidence in 4 yrs 3%
• Rates increased with
– Age (70-79) risk 8x
– SS (moderate to severe) risk 3x
– Baseline Qmx <12 risk 4x
– Prostate volume > 30cc risk 3x
– BPH related surgery : 16 /1000 py
– Cumulative incidence in 4 yrs 3%
• Rates increased with
– PSA > 1.4 risk 4x

54. 54
OCS

55. 55
In a nutshell …..
• Olmstead tells us that ,if left untreated
• Rise of IPSS 0.2/yr
• Qmax decreases 2%/yr
• TRUS vol increases 2%/yr (mean 0.6cc)
• Incidence of AUR 7/1000-yr
• Incidence of BPHRS 16/1000-yr
• Cumulative incidence of AUR 3% in 4 yrs
• Cumulative incidence of BPHRS 3% in 4 yrs

56. 56
Why is longitudinal community
study better than placebo arm
of RCTs in looking at natural
history?

57. 57
Problems with placebo arm of RCTs
• Strict inclusion criteria leads to regression to
mean effect (RMA)
– eg. PLESS placebo group : patients with the lowest
PSA actually improve their IPSS and Qmx with time
• Placebo
effect
• Possible
Hawthorne
effect

58. 58
Hawthorne effect & RMA
• The Hawthorne effect is a form of reactivity whereby
subjects improve or modify an aspect of their behavior
being experimentally measured simply in response to the
fact that they are being studied, not in response to any
particular experimental manipulation.
• regression toward the mean is the phenomenon that if
a variable is extreme on its first measurement, it will tend
to be closer to the average on a second measurement,
and—a fact that may superficially seem paradoxical—if it
is extreme on a second measurement, will tend to have
been closer to the average on the first measurement

59. 59
What is the risk that I run into
retention ?

60. 60
Retention
• Olmstead
– Cumulative incidence 3% in 4 yrs
– 7 / 1000 person-yr (increase with age)
• 40-49 mild/mod/severe symptoms 3/1000py
• 70-79 mild 9/1000py mod-severe 34/1000py
• MTOPS : 2% in 4.5 yrs
• PLESS : 7% in 4 yrs

61. 61
What are the risk factors for
progression (AUR)?

62. 62
• Olmsted risk factors
1. Age (70-70 8x vs 40-49)
2. Baseline symptom score > 8 (3x moderate c.f. mild)
3. Qmax < 12 (4x vs >12)
4. Large PVR >50cc at baseline (3x vs <50cc)
5. Prostate vol >30cc (3x vs <30cc)
6. PSA > 1.4 (risk 4x)
• Most important
(1/3 of TURP presented with retention of urine)
• Other risk factor:
– Failure to response to medical therapy [Emberton JU2006]
– Deterioration of symptom while on txn
– Presence of inflammation on prostate biopsy [Mishra BJU2007]
• Thus I will look into these factors and counsel the
patient accordingly

63. 63
Girman

64. 64
Girman

65. 65
What is the chance that I will
need a surgery?

66. 66
• Ball study: 10% in 5 yr
• OCS: 3% in 4 yr
Overall, only a minority of patient will require
surgery, thus the reason of WW and
Medical therapy

67. 67
What are the possible
complications of BPH?
How common are they?

68. 68

69. 69
Treatment of BPH

70. 70
Treatments for LUTS, BPH,
BOO
• Watchful waiting
• Medical therapy
– 5α-reductase
inhibitors
α-blockers
– Combination therapy
– Phytotherapy
• Office-based treatment
– TUMT
– TUNA
– WIT
• Surgicenter/
hospital-based treatment
– TURP (gold standard)
– TUIP
– Open surgery
– TUVP
– ILC
– VLAP
– Prostatic stents

71. 71
What are the important factors
in treatment of LUTS/BPH??
Degree of bothersome
Risk of progression

72. 72
What is the treatment option of WW?
• Mild to moderate LUTS
• Moderate to severe symptoms without bothering
• Components for WW
– Reassurance, education and explanation to patients
– Lifestyle advice : esp for storage LUTS
• Reasonable fluid intake, timed voiding
• Reduction of fluid before bedtime (nocturia)
• Avoidance of caffeine and alcohol
• Avoiding medications like antihistamine
• Double voiding and urethral milking (sense of incomplete
voiding and post-micturition dribble)
• Distraction technique for irritative LUTS
• Avoid constipation
– Periodic reevaluation with SS, UFR and PVR to check
for Progression

73. 73
What is the evidence of WW?
• Option for many men as few, if left
untreated, will progress to acute urinary
retention and complications
• Some men’s symptoms may improve
spontaneously, while others’ symptoms
remain stable for many years
• IPSS in Placebo group from PLESS study
even decrease 1.3 after 4 years

74. 74
What is the evidence of WW?
• Ball study (AJ Ball, P Abrams et al, BJUI
1981)
• 100 men with LUTS FU 5 yrs
– 25% get better, 30% get worse, 40% same
• 2% AUR, 10% require surgery

75. 75
What is the evidence of WW?
• Wasson et al NEJM 1995/ 5 yr results (Flanigan JU 1998)
• (~550) men with moderate symptoms randomised to WW to TURP
• 85% of men will be stable on WW at 1 year, deteriorating
progressively to 65% at 5 years
• 1/3 of patients crossed over to surgery in 5 years,
leaving 2/3 doing well in the WW
• surgery had improved bladder function over the WW
group (flow rates and postvoid residual [PVR] volumes),
with the best results being in those with high levels of
bother
• Increasing symptom and RU seem to be strongest
predictor of failure of WW

76. 76

77. 77
What is the mechanism of
AARB?
What is the mechanism of their
side effects?

78. 78
BPH – Medical Therapy
Adapted from Roehrborn CG Curr Opin Urol 2001;11:17-25; National Cancer Institute. NIH Publication No. 99-4303, 1999.
Alpha blockers 5-Alpha reductase inhibitors
Improve symptoms
and increase urinary
flow rate by relaxing
prostatic and
bladder-neck
smooth muscle
through sympathetic
activity blockade
Improve symptoms,
increase urinary flow
rate, and prevent BPH
outcomes by reducing
prostate enlargement
through hormonal
mechanisms

79. 79
• Mechanisms
– Relaxation of the dynamic smooth muscle component in the
stroma of the prostate via competitive antagonism at the A1R
– Reduce prostate tone and bladder outlet obstruction
• It has been shown that α-blockers have little effect on
urodynamically determined bladder outlet resistance
– For female bladder neck, not supplied by adrenergic nerves
• So other proposed mechanisms
– Induction of apoptosis
• Doxazosin and terazosin have been shown in vitro to induce
apoptosis in prostate cells independent of the A1R (but
contrary to this is the lack of change in size of the prostate
seen clinically)
• By working at extraprostatic sites
– Detrusor (by increasing blood flow)
– Spinal cord ?

80. 80
What is the efficacy of
AARB?

81. 81
Djavan
• Meta-analysis 1999 of AARB [EU]
– Response rate : 30-40%
– Reduce SS by 30% (4pt)
– Improves Qmx by 16-25%
• All alpha·1-adrenoceptor antagonists (alfuzosin,
terazosin, doxazosin and tamsulosin) produce
comparable improvements in LUTS and urinary flow
• Max effect at ~4weeks
• No reason to prolong for more than 1 month if not
efficacious
• 1/3 of men will not experience SS reduction

82. 82
Summary
Terazosin Doxazosin Alfuzosin Tamsulosin
Qmax rise 0.6-2 1.4-3.5 1.3 1.3-1.7
SS drop 1-2.3 2-4 1.6 2.3-3.2

83. 83
How many types of Alpha 1
receptors are you aware of?

84. 84
Alfa1-adrenoceptor (AR)
• Mediate prostates smooth muscle contraction
• Alpha 1 receptor (A1R) can be divided, based on molecular cloning
and in vitro studies
– High affinity for prazosin :
• A1aR, A1bR and A1dR
– Low affinity for prazosin :
• A1LR (may represent a functional phenotype of A1aR)
– A2R
• All three high affinity types have been demonstrated in the prostate
stroma (influence of SM tone)
– 70% predominance A1aR
• Glandular prostate has A1R with A1bR predominating, significance
unknown
• Inferred that dynamic component of the prostate smooth muscle is via
activation of the A1aR but the contribution of the other subtypes are
not clear

85. 85
• Other areas where A1R are found
– Bladder : AAR expression low but mainly A1dR
• Change may occur with obstruction
– Urethra : A1aR mainly
– CNS and spinal cord :
• A1aR widely distributed in brain with A1dR predominance in
spinal cord
• A1aR and A1bR may take part in inhibitory synapses from
CNS onto the voiding reflexes
– Vas : A1aR predominance
– Vascular tree : all types of AAR can be found
(including A2R)

86. 86
AR classification
• According to selectivity: but show “class effect”
• No study has directly compare one alpha-
blocker to another in terms of efficacy or side
effect
• Non selective: phenoxybenzmine
• Alfa-1: prazosin , alfuzosin
• Long acting alfa-1: terazosin , doxazosin ,
alfuzosin XL
• Selective Alfa 1a: Tamsulosin

87. 87
• Rapid relief of symptoms and improvement of
flow rate (days)
• Effective regardless of prostate size3
– Reduces symptoms equally well in patients
with and without BOO
• Effective irrespective of patient symptom (mild ,
moderate or severe)
• Effective across all age group
• Do not reduce prostate size
• Do not prevent AROU
AARB : Summary

88. 88
Summary: α-Blockers
• All alpha-blockers seen to have similar efficacy in
improving symptoms and flow
• Tamsulosin has less effect on blood pressure than
alfuzosin (especially in elderly patients) and causes less
symptomatic orthostatic hypotension
• Tolerability of alfuzosin and tamsulosin is similar and
better than other agent
• Benefit of alfa1-AR has shown to be better than placebo
and finasteride in men with LUTS by RCT
• Low risk of morbidity2
• Differences between agents with regards to
– Cardiovascular side effects
– Sexual side effects: more retrograde Ejaculation in
Tamsolusin
– More vasodilatory SE with alfulzosin

89. 89
What are the side effects of
AAR?

90. 90
What are the side effects of
AAR?
1. Asthenia, dizziness – 10%
2. Postural hypotension (1%)
– doxazosin and terazosin > alfuzosin and tamsulosin
3. Impotence (5-8%)
4. Retrograde ejaculation (8%)
– 1% with doxazosin, terazosin, alfuzosin (Djavan)
– 4% with tamsulosin 0.4mg (Djavan) – more
5. Rhinitis
– Tamsulosin
• In studies, up to 30% withdraw because
– Lack of efficacy
– Adverse effects

91. 91
What are the practical
considerations?
• Dose titration is used to initiate treatment with
doxazosin and terazosin
• This is not necessary with alfuzosin and
tamsulosin.
• AARB do not affect libido
• AARB has small beneficial effect on erectile
function but sometimes cause abnormal
ejaculation (mechanism unknown)
• Can be consider for intermittent use because of
rapid onset of action

92. 92
What is IFIS?
• Intraoperative floppy iris syndrome
• First reported in 2005 in cataract surgery
among patients taking tamsulosin
Chang DF, Campbell JR. Intraoperative floppy-iris syndrome associated with tamsulosin
(Flomax). J Cataract Refract Surg 2005; 31:664–673
• Triad of intraoperative findings during cataract
surgery
1. Poor preoperative pupil dilation
2. Iris billowing and prolapse
3. Progressive intraoperative myosis

93. 93
• Incidence:
– Up to 90% in the largest prospective study to date
(17% mild, 30% moderate, 43% severe)
– 50% in other retrospective reports
– (0-15% in patients taking non selective AARB)
• Has been reported in patients taking
1. Other non selective AARB
2. Finasteride
3. Saw palmetto
4. Some antipsychotic meds with alpha receptor
blocking features
• Tamsulosin : More frequently & more severe
state than other non-selective AARB

94. 94
• Pathophysiology
– A1a is the predominant alpha receptors in iris
– Systemic tamsulosin blocked contraction of
the iris dilator smooth muscle
– Deficient muscle tone led to poor pupil
dilation, iris floppiness, and a propensity to
prolapse
– Increases the cataract surgical complications :
iris damage and posterior capsule rupture

95. 95
Stopping the Rx
• But stopping the drug has not been shown
to decrease incidence of IFIS in
prospective studies
• IFIS was first reported in patient who has
stopped tamsulosin x 1 yr

96. 96
Management
• A variety of pharmacologic and surgical
strategies by ophthalmologists
– Topical atropine
– Intracameral a-agonist injections
– Pupil expansion rings etc
• 21% thought that all patients about to be started
on tamsulosin should be routinely referred for
eye examination
– 2/3 of respondants stated they would not take
tamsulosin themselves in future

97. 97
MCQ ?T/F
• With respect to the intraoperative floppy iris
syndrome
1. Has been reported in patients after taking
finasteride
2. Occurs more commonly in men taking
tamsulosin than other alpha blockers
3. Can be prevented by stopping alpha blockers
before cataract surgery
4. If unexpected, it increases the complications of
cataract surgical complications

98. 98
MCQ 2
• T – has been reported in patients after
finasteride, saw palmetto, AARB
• T – yes because of the Alpha-1A
receptors in iris muscle
• F – of unproven benefit
• T

99. 99
How does 5ARI work?

100. 100
Two types of 5AR (testosterone to
DHT)
• Type 1 : predominance in extraprostatic tissue
(skin, liver), role in BPH remains unclear
• Type 2 : predominance in prostate but also
expressed in extraprostatic tissue, for prostatic
growth, development and hyperplasia process
• Testosterone: DHT in prostate is 1:5
• Causes apoptosis and atrophy of the epithelial
part of the prostate
• Reduce the “static” component of BPH
• Prostate size reduction: 20-25%
• PSA level: ½ after 6-12m of treatment

101. 101
What is the result of dutasteride
VS finasteride?
• Finasteride: Type II inhibitor (5mg)
• Dutasterdie : Type I & II inhibitor (0.5mg))
• Both reduce prostate DHT concentration
by 90%
• Indirect comparison between individual
studies and one unpublished direct
comparative trial indicate that dutasteride
and finasteride are equally effective in the
treatment of LUTS

102. 102
What are the indications of
5ARIs?

103. 103
Indications
• Men with LUTS and an enlarged prostate (> 40cc)
• Boyle meta-analysis of RCTs concluded that finasteride
only be useful if prostate gland > 40cc
• Those with risk for progression – PLESS and MTOPS
can reduce progression
• Effective treatment for refractory hematuria due to
prostate bleeding
– Suppression of VEGF
– Insufficient data to use 5AR before TURP to reduce bleeding

104. 104
What is the efficacy of
5ARIs?

105. 105
ProscarProscar
• PLESS [MaConnell NEJM 1998]
• 4 yrs of Proscar vs placebo
– Increase of Qmax 1.9ml/s (placebo 0.2)
– Decrease in SS by ~3 (placebo 1.3)
– Reduce risk of AUR by ~60% (5% vs 10%)
– Reduce risk of BPHRS by ~60% (3% vs 7%)
– Reduce prostate size by 20% (vs 15% in placebo)
• AUA
– Less effective in improving LUTS than alpha-blocker
• Proscar Long Term Efficacy & Safty Study

106. 106

107. 107
EAU
• Only suitable for long term treatment
• After 2-4 yr of treatment:
– Reduce symptom score by 15%
– Reduce prostate volume: 20-25%
– Increase Qmax: 2ml/s
• Symptom reduction not better than placebo if prostate
size < 40cc
• Dutasteride reduce IPSS, prostate volume & AROU and
increase Qmax even if prostate 30-40cc
• Reduce symptom slower than AARB
• Reduce risk of AROU better than AARB
• Reduce blood loss during TURP (decrease
vascularization)
• High PSA & large prostate seems to be most
beneficial

108. 108
What are the side effects of
Proscar?

109. 109
PLESS
• Decreased libido 6%
• ED 8%
• Ejaculate disorder (retrograde, failure , decrease
semen volume) 4%
• Rash, breast enlargement, tenderness1%
• Most of these occur during the 1st
yr and does
not increase over time
• But leads to withdrawal from PLESS in 30%

110. 110
How does 5ARI affect PSA and
does that mask the early
detection of prostate cancer?

111. 111
EAU
• 5ARI lower the PSA by ~50% after 1 yr.
• Both the PLESS Study Group & Finasteride
PSA study Group (Andriole Urology 1998 and
Oesterling Urology 1997) have verified that :
• doubling the PSA value after taking
finasteride allows appropriate interpretation of
PSA and 5ARI does not mask the detection
of prostate cancer.
• Histologically it has also been shown that
5ARI does not cause problems with
interpretation of TRUS Bx (PLESS study
Group Yang Urology 1999)

112. 112
What are the role of
antimuscarinics?

113. 113
What are muscarinic receptors?
• Five muscarinic receptor subtypes (M1-M5) have been
described in humans, of which the M2 and M3 subtypes
are predominantly expressed in the detrusor
• Although approximately 80% of these muscarinic
receptors are M2 and 20% M3 subtypes, only M3 seems
to be involved in bladder contractions in healthy humans
• The role of M2 subtypes remains unclear. However, in
men with neurogenic bladder dysfunction and in
experimental animals with neurogenic bladders or
bladder outlet obstruction M2 receptors seem to be
involved in smooth muscle contractions as well

114. 114
How dose bladder contraction
mediated?
• Scaral (S2-4) micturition centre connet to
bladder via pelvic nerves
• Acetlcholine stimulate post-synaptic
muscarinic receptor  G-protein mediated
Ca release  opening of Ca channels 
SM contraction
• Anticholinergic inhibitsmuscarinic receptor
stimuation  reduce SM cell contraction

115. 115
What is the use of
antimuscarinic in BPH?
• Muscarinic receptor antagonists might be
considered in men with moderate to
severe LUTS who have predominantly
bladder storage symptoms
• This drug should be used precautiously if
residual urine >250-300ml

116. 116
Is antimuscurinic safe?

117. 117

118. 118
What is the evidence of
Antimuscarinic vs Placebo?
• Randomized, placebo-controlled
trials demonstrated that Tolterodine
can significantly reduce:
1. Urgency incontinence
2. Daytime or 24-hour frequency
3. Urgency related voiding
– Roehrborn et al, et al. Extended-release tolterodine with or
without tamsulosin in men with lower urinary tract symptoms
and overactive bladder: effects on urinary symptoms assessed
by the International Prostate Symptom Score. BJU Int. 2008
Nov;102(9):1133-9. Epub 2008 May 26.

119. 119
What is the evidence of
antimuscarinic?
• If treatment outcome was stratified by PSA,
tolterodine significantly reduced daytime
frequency, 24h voiding frequency and IPSS
storage symptoms in those men with PSA
concentrations below 1.3 ng/mL, which was not
the case in men with PSA of 1.3 ng/mL or more
indicating that men with smaller prostates might
profit more from antimuscarinic drugs
– Roehrborn CG, Kaplan SA, et al. Effects of serum PSA on efficacy of tolterodine
extended release with or without tamsulosin in men with LUTS, including OAB.
Urology 2008 Nov;72(5):1061-7

120. 120
Urodynamic effect of
Antimuscurinic
• Larger bladder volume to first detrussor
contraction
• Higher maximum MCC
• Decrease bladder contractility index
• Qmax is unchange
• Short term txn to men with BOO is safe

121. 121
What are the side-effects of
antimuscarinic?
1. Dry mouth - 25%
2. Constipation (4%) similar to placebo
3. AROU and increase of postvoid residual urine
in men without bladder outlet obstruction is
minimal and not significantly different
compared to placebo
4. Nasopharyngitis (3%)
5. Dizziness (5%)
6. Withdrawal rate – 10%
– Withdrawal due to side-effect <1% (no diff from
placebo)

122. 122
Will it cause retention?
• Increase PVR is minimal and no different from
placebo
• Fesoterodine 8mg show higher PVR than
fesoterodine 4mg or placebo
• Incidence of AROU is comparable to placebo
• Men with BOO : not recommended due to
theoretical risk
• Generally recommend that not for PVR > 200ml
and Qmax < 5ml/s

123. 123

124. 124
What are the studies :
antimuscarinics + AARB?
TIMES JAMA2006
• LUTS +OAB, no prior Rx
• Tolterodine SR (Tsr) + tamsulosin (T) ,either therapy,
placebo
• Tsr +T in general more efficacious than either one
• Tsr = Tsr +T in low PSA and small prostate
• Tsr +T suggested for high PSA and high prostate vol
• Exclude PVR > 40% of CC
• Conclusion: Combination therapy is more efficacious then
mono therapy , esp in pt with high PSA + prostate volume

125. 125
ADAM Pfizer data
• On alpha1 blockers with persistent OAB
• Randomized to continue alpha-1-blockers with Tsr or
placebo
• Did not improve PPBC
– PPBC,:patient perception of bladder condition
• Tsr :Improve OAB Sx
• Tolterodine SR well tolerated
– Significant increase in PVR (13.6ml)
– No increase in AUR
– No decrease in Qmax
• Conclusion: Pt on AARB with persistent OAB
will have improved sym when adding Tsr

126. 126
What are the recommendations
of combination therapy?
• Combination treatment with α-blocker and
muscarinic receptor antagonist might be
considered in patients
– with moderate to severe LUTS if symptom relief has
been insufficient with the monotherapy of either drug
– More effacicious with pt with high PSA + prostate
volume
• Combination treatment should cautiously be
prescribed in men who are suspicious of having
bladder outlet obstruction

127. 127
What phytotherapeutic
agents are you aware of?

128. 128
Is there any role of
phytotherapy?
• EAU Guidelines committee is unable to
make specific recommendations about
phytotherapy of male LUTS because of
the heterogeneity of the products and the
methodological problems associated with
meta-analyses

129. 129
Phytotherapy
• Saw Palmetto berry (Seronoa Repens)
– Anti-inflammatory , antiproliferative , oestrogenic drug
with 5ARI activity
– Previous Meta-analysis : 40% reduction in symptom
score (same as finasteride) [ Wilt JAMA 1998]
– Recent study: no difference vs placebo (see below)
• South African Star Grass (Harzol)
– Contain beta-sitosterol
– Cause apoptosis in prostate stromal cell
– RCT vs placebo: 5pt improvement of SS over placebo
• Others: African plum (Pygeum Africanum)

130. 130
What is the evidence of Saw
Palmetto for BPH?
• Mode of action is unknown
• Double-blind trial, randomly assigned 225 men > 49yo
• Moderate-to-severe symptoms
• One year of treatment : saw palmetto (160 mg BD) or placebo
• Result: There was no significant difference in
1. Change in AUASI scores
2. Qmax
3. Prostate size
4. Residual volume after voiding
5. Quality of life, or serum prostate-specific antigen levels
6. The incidence of side effects was similar in the two groups
• Conclusions: In this study, saw palmetto did not improve symptoms
or objective measures of benign prostatic hyperplasia
N Engl J Med 2006;354: 557-66

131. 131
Desmopressin

132. 132
What is the role of
desmopressin?• Indication: Nocturia with a polyuric background
• MOA:
– Synthetic analogue of vasopressin
– Anti-diuretic effect: increase water re-absorption & urine
osmolality, decrease water excretion & urine volume
– Only V2 affinity: No V1 effect (HT , vasoconstriction)
– Effect of reduce urine volume last 8-12 hour
• Form: IV, Nasal spray , tablet, MELT
• Dosage:
– Initiated at a low dose (0.1 mg/day) PO nocte
– Gradually increased every week until maximum efficacy is
reached
– The maximal daily dose recommended is 0.4 mg/day
• Usage:
– Patients should avoid drinking fluids at least 1 hour before using
desmopressin until 8 hours thereafter

133. 133
• Effect:
– Reduced nocturnal diuresis : 1ml/min
– Reduced number of nocturia: 2x /night
– Extend time to first nocturia by: 1.6 hour
– Reduce % of urine volume excreted at night
• Side effect:
– Headache, naeusea, diarrhoea, abd pain , dizziness , dry mouth
– Hypo Na (< 130mmol/L) (5%)
– Peripheral edema & HT
• Cautions:
– Risk of Hypo Na is 8x in pt > 65yo
– Men aged 65 years or older, desmopressin should not be used if
the serum sodium concentration is below the normal value
– In all other men aged 65 years or older, serum sodium
concentration should be measured at day 3 and 7 as well as
after 1 month and, if serum sodium concentration has remained
normal, every 3-6 months subsequently

134. 134
PDE5 inhibitor

135. 135
LUTs and ED
• ED and LUTs strongly linked
• 4 theories of link between ED and LUTS
– NOS/NO theory
– Autonomic hyperactivity and metabolic Sx hypothesis
– Rho-kinase activation/ endothelin pathway
– Pelvic atherosclerosis
• both highly prevalent in aging men
• co-prescription of both drugs likely to increase
• PED5-i: increase concentration of cGMP 
reduce SM tone of detrussor , prostate and
urethra

136. 136
• Risk of combination therapy:
– Tadalafil : singificant drop of BP with doxazosin , hence to ↓ BP
effect, suggest alfuzosin/ tamsulosin to combine with PDE5i
– sildenafil should not be used in doses exceeding 25 mg within 4
h of taking an α1-AR antagonist
– Tamulosin → dose dependent anejaculation
• AARB on ED:
– Would not worsen ED
– Cardura XL & Alfulzosin may improve IIEF
• Combination Tx
– Pilot study n=62 with untreated LUTS and ED
– Randomized to alfuzosin 10mg QD, Viagra 25mg QD, or both for
12 weeks.
– IPSS improvement -24% for combination (-16% for alfuzosin/
-17% for Viagra)
– IIEF improvement +59% for combination (+17% for alfuzosin/
+50% for Viagra)
– Combination well tolerated with no serious adverse events

137. 137
What is the practical
consideration of PDE5 inhibitor?
• PDE5 inhibitors reduce moderate to severe male
LUTS but on effect on Qmax
• Officially licensed only for the treatment of
erectile dysfunction and pulmonary arterial
hypertension
• Treatment beyond this indication (e.g. male
LUTS) is still experimental and should not be
used routinely in the clinical setting
• Long-term experience in patients with LUTS is
still lacking

138. 138
What is the evidence of
combined therapy?
MTOPS
COMBAT

139. 139
Combination Therapy: RationaleCombination Therapy: Rationale
• 5ARIs and α-blockers have complementary
actions
–5ARIs act on the hormonal axis
α-blockers act on the adrenergic
receptors
• Main reported effects
α-blockers induce rapid symptom and
flow rate improvement
–5ARIs reduce risk of progression to
AUR or BPH-related surgery

140. 140
Indications
• Men with moderate to severe LUTS
• Risk of disease progression (large
prostate, High PSA, Advance Age, etc)
• Only be used with long-term treatment
(>12m) is intended
• Discontinuation of AARB after 6m might
be consider in men with moderate LUTS

141. 141
Major combination therapy trials
1. VA study Lepor H et al. N Engl J Med. 1996 Aug 22;335(8):533-9.
2. PREDICT Kirby RS et al. Urology. 2003 Jan;61(1):119-26
3. MTOPS McConnell JD et al. N Engl J Med. 2003 Dec 18;349(25):2387-98
4. CombAT Roehrborn CG et al. J Urol 2008;179(2):616-21
• But 1. 2. only look at symptom improvement,
no monitoring progression
• Both only 1 yr Fu
• Also smaller prostate size

142. 142
MTOPS
Medical Therapy of Prostatic Symptom
• McConnell, NEJM 2003
• 3047 men
• Inclusion
– Age > 50
– AUA-SS 8-30
– Qmx 4-15
• Excluded
– Prior medical / surgical Tx for BPH
– PSA >10

143. 143
MTOPS
• Randomised to placebo, finasteride, doxazosin
(4-8mg) and combination
• FU 4.5 yrs
• Aim was to find whether combination would
reduce BPH progression in terms of:
1. Rise of SS of 4 or more
2. AUR
3. Need for BPHRS
4. Incontinence
5. Recurrent UTI
6. Renal failure

144. 144
MTOPS

145. 145
MTOPS: Results
• Cumulative incidence of AUR in placebo
group 2% only
• Combination reduces risk of overall
progression by 66% vs placebo
– Better than both monotherapy as well
– Finasteride better than cardura XL in terms of
reduction risk of overall progression

146. 146
Individual progression events
• All compare to placebo
• AUR
– Combination reduces the risk by 80%
– Finasteride responsible for entire reduction of AUR
• BPHRS
– Combination reduces the risk by 70%
– Finasteride responsible for entire reduction of AUR
• Rise of IPSS by 4 or above
– Combination reduce the risk by 64%
– Doxazosin slightly better than Finasteride in terms of
symptom progression

147. 147
MTOPS

148. 148
MTOPS
• NNT to prevent overall progression
– Combine 8, finasteride 15, doxa 14
• NNT to prevent BPHRS
– Combination 26
• PSA > 4 : 23
• Prostate > 40cc : 40
– Finasteride 29
– Doxazosin 60

149. 149
MTOPS
• Risk factors for overall progression (among
those on WW / doxazosin)
– Prostate volume
– PSA
– Qmx
– Severity of symptoms
• Among those taking combination
– Only PSA predicts AUR / need of BPHRS
• Most important risk factor for BPH clinical
progression
– PSA
– Prostate volume

150. 150
MTOPS: Conclusion
1. Doxazosin, Finasteride and the combination all reduce
the risk of overall clinical progression. Combination more
effective than either drug alone
2. In reducing symptom score rise, combination therapy
more effective than monotherapy
3. In reducing risk of AUR and the need for BPH related
surgery, combination and finasteride equally effective
4. Doxazosin slightly delays the the time to AUR and BPH
related surgery but failed to reduce the risk of these of
events over the duration of the study
5. Combination resulted in greater improvement in AUA-SS
and Qmx than monotherapy alone

151. 151
MTOPS: conclusion
• Combination therapy is most effect in :
– Significant improvements in AUA score (−7.0
points) and maximum flow rate (Qmax; +3.7)
– Significantly reduced the risk of progression
(66%)
– Decreased risk of acute urinary retention
(80%) and/or invasive therapy (70%)
• Combination therapy is beneficial for
patient with larger prostate

152. 152
MTOPS: Conclusion
• Thus, we can conclude that of patient with
PSA > 1.5 ng/ml & prostate volume> 30,
combination therapy is more effective than
either monotherapy in terms of overall
clinical progression, reduction of SS &
improvement of Qmax
• Combination therapy is as effective as
Finasteride in reducing risk of AUR and
BPHRS

153. 153
MTOPS placebo group analysis
• Crawford et al J Urol 2006
• BPH progression overall
– 4.5 per 100 person-yr or 17% in 4 yrs
• Risk factors identified
1. TPV > 30cc
2. PSA > 1.5 (vs 1.4)
3. Qmx < 10.6 (vs 12)
4. PVR > 39
5. Age > 62 (vs >70)

154. 154
Can you think of reasons why
MTOPS’ results are at odds
with previous combination
trials?

155. 155
• Previous studies (eg. Lepor’s VA-Coop
study, PREDICT trial) only has short FU
(12months) whereas MTOPS ‘ FU is
longer
• Previous studies only look at Qmx and
symptom score but MTOPS look at
disease progression instead
• Prostates in the VA study postulated to be
smaller and thus Proscar of not much use

156. 156
ComBAT trial – 4 years resultComBAT trial – 4 years result

157. 157
CombAT
Combination of Avodart and Tamsulosin
• Multicentre double-blinded RCT
• 4800 men
• Age>50, IPSS >/= 12, prostate > 30cc, PSA 1.5-
10, PVR > 125, Qmx 5-15 (i.e. high risk for
progression)
• Randomised to tamsulosin, dutesteride 0.5mg,
combination (no placebo arm) x 4 yrs
• Endpoint at 2 yrs : Change in IPSS, patient
satisfaction, AUR, BPHRS
• Median prostate 49cc, mean PSA 3.5

158. 158
CombAT 4 yr data
• Roehrborn et al: Result
– Symptom improvement (IPSS)
• Combination treatment >> either monotherapies
• Starting from month 9
• REGARDLESS of stratification by prostate vol / PSA (with the
except of highest PSA tertile : >/= 4.4, where diff between IPSS drop by combo and
dutasteride not stat significant), baseline IPSS, BMI, Qmx, QoL and
whether there was medical treatment before
– Increase in Qmax:
• Combination >> either monotherapies
– Reduction of AUR:
• Combination >> α-blocker
– BPHRS:
• Combination >> α-blocker
– Patient reported QOL & treatment satisfaction
• Combination >> either monotherapies

159. 159
Dutasteride vs tamsulosin :
• IPSS : Dutasteride results in greater IPSS
drop than tamsulosin
• Raising Qmx : Dutasteride superior to
tamsulosin

160. 160
Take home
• As prostates get bigger (PSA higher), the benefit
brought about by combination becomes more
evident
• First time that 5ARI superior to AARB in lowering
IPSS and Qmax (in contrast to VA-Coop,
PREDICT, ALFIN, MTOPS§
– all prostates are on
average 36-41cc)
• Combination superior to either monotherapy in
patients regardless of treatment status
• This implies that dutasteride should be used as
1st line therapy in patients with IPSS > 16 and
enlarged prostates

161. 161
Limitations of study
• Men with previous “unsuccessful”
treatment with dutasteride / tamsulosin
were excluded from study – investigator
defined
• Absence of a placebo arm

162. 162
Take home
• The different results between the CombAT and MTOPS trials
appear to arise from different inclusion and exclusion criteria
• In both the CombAT and MTOPS: overall drug-related
adverse events were significantly more frequent during
combination treatment than during either monotherapy
– comBAT4 – 1% withdrawal rate due to sexual side-effect in combine
group
• Combination therapy should only be used when long-term
treatment (more than 12 months) is intended; this issue
should be discussed with the patient before treatment
• Discontinuation of the α-blocker after 6 months might be
considered in men with moderate LUTS

163. 163
• For AUR and BPH related surgery
o Outcome similar to MTOP (combination
tx superior to AARB but not 5ARI)
• For BPH clinical progression and
symptom deterioration of IPSS
o Combination therapy was significantly
superior to either monotherapy

164. 164
• Urologists had different points of view
regarding: the 48% to 57% relative risk
reduction promoted and the 1.9% to 2.4%
absolute risk reductions actually observed
in the median risk of AUR and surgery,
respectively” [PLESS; MTOPS]

165. 165

166. 166

167. 167
CombAT 4yr: AUR & BPHRH
• To investigate whether combination
therapy is more effective than either
monotherapy in reducing the relative risk
for
– Acute urinary retention (AUR)
– BPH-related surgery
– BPH clinical progression (symptoms, Qmax,
prostate volume)
• Over 4 yr in men at increased risk of
progression.

168. 168
AUR & BPHRS
• Combination vs Tamsulosin:
– RR reduction overall: 65%
– RR reduction AUR: 67%
– RR reduction BPHRS : 70%
• Combination vs dutasteride:
– RR reduction overall: 20%
– RR reduction AUR: 18%
– RR reduction BPHRS: 32%
• Time to event:
– significantly lower in combination vs tamsulosin
– No difference btw combination vs dutasteride

169. 169
BPH clinical progression
• Combination reduced RR of BPH
progression by:
– 44% vs tamsulosin
– 31% vs dutasteride
• Combination reduced RR of IPSS >4pt
by :
– 41% vs tamsulosin
– 35% vs dutasteride

170. 170

171. 171
Conclusion
• In men with moderate-to-severe LUTS due
to BPH, dutasteride and tamsulosin
combination therapy significantly reduced
the relative risk of AUR or BPH-related
surgery over 4 yr by 66% compared with
tamsulosin monotherapy
• No significant difference was observed
between combination therapy and
dutasteride

172. 172
Conclusion
• combination therapy significantly reduced the
relative risk of BPH clinical progression and
symptom deterioration of IPSS >4 points (the
most frequent progression event) versus both
monotherapies
• use of dutasteride and tamsulosin combination
therapy as a treatment option in men with LUTS
due to BPH and prostatic enlargement at
increased risk of progression to provide rapid
and durable symptom benefit and reduce the
long-term risk of BPH progression

173. 173

174. 174
CombAT 4yr: IPSS (storage &
voiding)
• Mean reduction of Storage subscore were significantly
greater in the combine gp vs:
– Dutasteride (-0.43)
– Tamsulosin (-0.96)
• Mean reduction in voiding subscore were significantly
greater in combine gp vs:
– Dutasteride (-0.51)
– Tamsulosin (-1.6)
• Improvement in storage score were observe from:
– Dutasteride : 3m
– Tamsolusin : 12m
• Improvement in voiding score were observed from:
– Dutasteride: 3m
– Tamsulusin : 6m

175. 175

176. 176

177. 177
• Improvement of IPSS with combine
therapy were achieved irrespective of
prostate volume
• Men with baseline prostate volume > 58ml
, combine therapy was not better than
dutasteride

178. 178
Conclusion
• In men with a prostate volume of ≥30 mL,
combined therapy with dutasteride plus
tamsulosin provided better long-term (up
to 4 years) control of both storage and
voiding LUTS compared with tamsulosin
monotherapy
• Combined therapy was better than
dutasteride monotherapy in men with
prostate volumes of ≥30 to < 58 mL, but
not in men with a prostate volume of ≥58
mL.

179. 179
Combination therapy (dutasteride +
tamusulosin) can
• Reduce AUR /BPHRS:
– Better than tamsulosin but not dutasteride
• Reduce BPH clinical progression/ IPSS:
– Better than both monotherapy
• Improves patient-record , disease specific QoL &
treatment satisfaction:
– Better than both monotherapy
• Controlling both storage & voiding symptoms:
– Better than both monotherapy
– Dutasteride can improve voiding symptom as from
effect of prostate volume , but also as effective as
alfa-blocker in the control of storage symptoms

180. 180
MTOPS vs CombAT
• Following reduction were observe:
– Overall risk of progression: 66% vs 44%
– Symptomatic progression: 64% vs 41%
– AROU: 81% vs 68%
– Urinary incontinence: 65% vs 26%
– BPHRS: 67% vs 71%

181. 181
Summary for combination therapy:
• 1 year symptom reduction:
– AARB >> 5ARI
– Combine = AARB
• MTOPS (4yr) , COMBAT (2-4 yr)
– IPSS/ Qmax: Combine >> either monotherapy
(effect start on 9m)
– AROU/ BPHRS : Combine= 5ARI >> AARB
(effect start on 8m)

182. 182
What is SMART study?
• Symptom Management After Reducing Therapy
– Combination of dutasteride and tamsulosin
– ¾ show No significant symptom deterioration after
discontinuing the alpha-blocker following 6 months of
combination therapy
– Patients with severe symptoms may benefit from
longer-term combination therapy
– Optimal duration of combination therapy prior to
withdrawal appears to be 6-9 month
• Barkin J, et al. Alpha-blocker therapy can be withdrawn in the
majority of men following initial combination therapy with the
dual 5alpha-reductase inhibitor dutasteride. Eur Urol 2003
Oct;44(4):461-6.

183. 183
What are the baseline and
dynamic variables for BPH
progression? (AUR)
Please provide evidence

184. 184
Khastgir et al NCPU 2007

185. 185
• Baseline variables
– Age (OCS : 70-79)
– Symptoms score (OCS : IPSS > 7 ie. Moderate to severe)
– Qmax (OCS : <12)
– Prostate size (OCS : >30cc, pMTOPS > 30cc, pALTESS
> 50cc )
– PVR (OCS > 50cc, pALTESS > 93cc)
– PSA (pMTOPS : > 1.5, pPLESS >7, pALTESS > 2.3)
– Most important are the PSA and the prostate volume
– (UK : PSA > 1.4 and Vol > 30cc)

186. 186
• Static / baseline
– Age (Olmsted)
– Qmx (Olmsted)
– IPSS (Olmsted, MTOPS)
– TRUS vol (Olmsted, MTOPS, ALTESS)
– PSA (MTOPS, PLESS, ALTESS)
– PVR (Olmsted, MTOPS, ALTESS)

187. 187
• Dynamic variables (ALF-ONE)
– Previous AUR (3x)
– Rise of IPSS 4 or above despite alfuzosin
10mg daily (2.5x)
– Bothersome score >3 despite alfuzosin 10mg
daily (8x)

188. 188
ALTESS
• Alfuzosin Long Term Efficacy and Safety
• Double blinded Alfuzosin vs placebo for BPH
progression
• Patients after progression not censored (unlike
MTOPS)
• High risk for progression patients
• Risk of progression (AUR)
– PSA (>2.3 more risk than <2.3)
– TRUS vol (>50cc more risk than <50cc)
– PVR (>93cc more risk than <93cc)

189. 189
ALFONE study
• Open labelled study to study the response
of patients to alfuzosin 10mg QD
• Inclusion criteria deliberately broad (men
with prev AUR included as well)
• Able to shows response to Alfuzosin as
dynamic predictors of progression

190. 190
ALFONE
• Risk factors of AUR - . previous AUR
managed medically, increasing age,
raised PSA, lack of response to alpha
blockers
• Static risk factors
– Previous hx of AUR (3x risk)
• Dynamic risk factors
– Bothersome score of >3 during Tx (8x)
– Increase of IPSS of 4 or above during Tx
(2.5x)

191. 191
UK perspective on BPH Mx

192. 192

193. 193

194. 194

195. 195

196. 196
Surgery
• Indication
• TURP
• TURis
• Laser: PVP, Homium base
• TUMT & TUNA
• Open surgery
• Others

197. 197
What are the indications for
TURP?

198. 198
• Absolute
1. Refractory / recurrent urinary retention
2. BPH with renal insufficiency
3. BPH with bladder stones
4. BPH with recurrent urinary tract infection
5. BPH with recurrent hematuria refractory to medical
treatment
• Relative
– Moderate to severe LUTS refractory to medical
treatment
– Bothersome LUTS who does not want medical
treatment (due to their lower reduction in SS)

199. 199
What is the efficacy of
TURP?

200. 200
EAU
• TURP/TUIP/Open :
– Urinary symptom score improves in about
85% of patients undergoing TURP
– Improvement of SS by 70%
– Increase in Qmx by 115% (10)
• Open increase by 175% (8-23)
– Reduce post void volume by 50-60%
• Voiding symptom improve much more
quickly than storage symptom

201. 201
How do you counsel a
patient towards TURP?
Any well-known TURP series?

202. 202
EAU/ textbook
• Early complication:
– Anase related, Ischemic , DVT
– Blood transfusion 2%
– Sepsis 3%
– TUR syndrome <2%
• 0.8% vs 1.5% (45gm)
• 0.8% vs 2% (>90min)
– Peri-op mortality 0.3%
• After TURP
– Incontinence 2.2% (Open 10%)
– Urethral stricture 4% (Open 3%)
– BNS 4% (Open 2%, TUIP <1%)
– Retrograde ejaculation 65-70% (Open 80%, TUIP 40%)
– ED
• Marberger metaanalysis review 10%
• Wasson study : no difference with placebo
• Re-treatment rate:
– For TURP / TUIP / Open 1-2% / yr

203. 203
Counseling
• Difference btw TURP done for AUR vs LUTS:
– More intraoperative and major postoperative complications [NPA,
Mebust]
– More incidence of reoperation (mainly for bleeding) [NPA]
– More cannot pass urine postop (9 vs 2.3%) [NPA, Mebust]
– Higher mortality (IP, 30d, 90d) [NPA]
– No diff in outcome [NPA]
– Higher incidence of underlying hypotonic bladder [Mebust]
• Patients with renal impairment (serum creatinine 1.5mg. % or
greater) have significantly higher postoperative complications
[Mebust]
• Failed TWOC after TURP:
– 40% in acute on chronic retention
– 10% in AROU
– 1% overall

204. 204
National Prostatectomy Audit
• UK based large scale audit
• 5361 prostatectomies in 5 UK regions
collected in 6 months
• 23% done for AUR
• 97% transurethral prostatectomy

205. 205
National Prostatectomy Audit
• Those undergoing prostatectomies for AUR
– Older, higher ASA class and more with impaired renal function
– Larger prostates
– Found to have more intraoperative and major postoperative
complications, more incidence of reoperation (mainly for
bleeding)
– More cannot pass urine postop (9 vs 2.3%)
– Higher mortality (IP, 30d, 90d)
• Only part of the adverse outcome can be explained by
the confounding variables at stat analysis
• No diff in outcome between those having prostatectomy
for AUR vs LUTS

206. 206

207. 207

208. 208
NPA
• Intraoperative
– Complications 3%
• Bleeding req
transfusion > 2u 3%
• Extravasation <1%
– AUR cases
• Complications 5%
• Bleeding req
transfusion > 2u 8%
• Extravasation <1%
• Postoperative
– Complication 7%
• Failed to void 9%
• Permanent <1%
• Secondary hemorrhage
1%
• TUR syndrome <1%
– Death 0.2%
• 0.7% among AUR
cases

209. 209
National Prostatectomy Audit
• Complications of TURP (long term)
– Retrograde ejaculation 70%
– ED 30%
• No significant difference in ED between WW and
TURP in Wasson group
– Early incontinence rate of 33% at 3 months
and a 6% long term incontinence

210. 210
TURP : Immediate and postoperative
complications. Cooperative Study of
13 Participating institutions evaluating
3885 patients
Mebust et al JU 1989

211. 211
Method
• 3885 from 1978 to 1987 TURPs
retrospectively reviewed
• Nationwide cooperative study involving 13
institutions organised by the AUA
• Results compared with past similar series
– Holtgrewe et al 1962
– Melchoir et al 1974

212. 212
Results
• Intraoperative
– Mean resected tissue 22g
– Complications 6.9%
• Transfusion 2.5%
• TUR 2%
• Cardiac arrhythmia 1.1%
• Non-fatal AMI 0.05%

213. 213
Results
• Postoperative
– 0.23% postoperative death / mortality
• Cause predominately sepsis
– 18% postop complication
• Transfusion 3.9%
• Clot retention 3.3%
• Unable to void 6.5% (2.4% needs to leave hospital
with a catheter)
– Hypotonic bladder in 55%

214. 214
Analysis
• Patients with renal impairment (serum creatinine
1.5mg. % or greater) have significantly higher
postoperative complications
• No relationship between gland size and whether
there is postop failure to void
• TURPs for AUR have
– Higher postop complication rates
– Higher postop retention rates
– Higher incidence of underlying hypotonic bladder

215. 215
Analysis
• Mortality less than previously two series
(1.3-2.5%) but complication rates similar
• Risk factors identified for postop morbidity
• Large scale study looking at TURP
– Safe operation with minimal mortality
– Complication rate however still significant

216. 216
Mebust 1989
• Intraoperative
– Complications 7%
• Bleeding req
transfusion 2.5%
– Majority < 2u
• Arrhythmia 1%
• Extravasation 1%
– Majority treated
conservatively OK
• Non-fatal MI <0.1%
• TUR syndrome 2%
– Death 0%
• Postoperative
– Complication 18%
• Failed to void 7%
• Bleeding req
transfusion 4%
• Clot retention 3%
– Death 0.23%
• 0.1% among benign
pathologies
• Includes sepsis, AMI

217. 217
TUR syndromeTUR syndrome

218. 218
What is the evidence of
Perioperative antibiotics?
• A known urinary tract infection should be
treated before surgery
• The routine use of prophylactic antibiotics
remains controversial
• Antibiotics are recommended in patients
on catheterisation prior to surgery

219. 219
TUR syndrome
• Incidence 0.5-2% (Mebust et al 1989)
• Diluational hypoNa & Fluid overload
• Mental confusion, nausea, vomiting,
Hypotension, tachy/bradycardia and visual
disturbance
• Na < 125mmol/dL
• Increased risk if gland >45g (1%>2%),
resection time >90mins (1%>2%)

220. 220
What is irrigation fluid in TUR?
• 1.5% glycine
• Inhibitory amino acid
• Non-electrolyte, non-hemolytic solution (water may
cause hemolysis)
• Osmolarity: 200 mOsm/l (hypotonic to plasma)
• Absorption of rate: 20ml/min
• TUR syndrome develop after absorption of 2 L
• Fluid absorption double when height of fluid changed
from 60-70cm
• 60cm H20 is the minimal height to maintain good vision
field
• 90% metabolized in liver ammonia, glycolic acid, H20
• 10% metabolized in kidney

221. 221
What is pathogenesis of TUR
syndrome?
Pathophysiology Manifestation
Dilutional
hyponatremia
Osmotic shift of water from plasma
into brain
•Cerebral edema
•Coning
130-135: asymptomatic
120-130: restless, confusion
115-120: nausea
<115: seizure, coma
Fluid overload •Pulmonary edema
•Cardiac failure
Early
• Hypertension
•SOB
•Chest pain
Late
•Bradycarida
•hypotension
Glycine,
metabolised by
GABA pathway
and ammonia
toxicity
•Inhibitory neurotransmitter in retina
•Direct CNS and cardiotoxicity
•Induce ANPnatriuresis
Visual disturbance (flashing
light)
Opisthotonous
Cerebral irritation

222. 222
How to manage TUR syndrome
1. Prevention
• Identify patient at risk (>45g, resection time> 90 mins), consider open if
glands> 100g
• Keep height of irrigating fluid to minimum
• Try to finish TURP if capsule breached
• Prophylactic administration of diuretics
• Use bipolar or laser resection with NS irrigation
• Comparable result with less catheter time and shorter hospital stay
2. Detection
• Spinal anaesthesia to detect early features: visual, nausea, vomiting, confusion
• Hypertension, arrhythmia, decreased oxygen saturation
• Check abd for sign of extravasation
• 1% ethanol in irrigant-> check breath ethanol level assess amount of fluid
absorbed
3. Treatment
• Check serum electrolyte
• Loop diuretic, eg 40mg lasix
• Quick hemostasis and finish TURP
• Central line and arterial monitoring in ICU
• Fluid restriction, diuretics and Hypertonic saline solution
• corrrection of 1mmol /litre per hour to avoid central pontine myelinolysis

223. 223
When would you perform a
TUIP rather than TURP?

224. 224
• TUIP indicated in
– BPH with prostate <30g and absent middle
lobe : in this group of patients the
improvement is similar to TURP but TUIP is
faster and with less complication such as
retrograde ejaculation (40% vs 70%)
– Slightly higher rate of secondary procedure
– Primary bladder neck obstruction proven on
VUD study

225. 225
What are the factors predicting
complications after TURP?

226. 226
Mebust 1989
• Resection time > 90mins
• Gland volume > 45mls
• AUR
• Age > 80 years
• Black population
• Also the presence of preop renal impairment
increases the rate of postop complication (from 17
to 25%)
– Sterile preop urine perioperative antibiotics was shown to
decrease infection risk (decrease from 2-10% to near 0%)

227. 227
70-yr-old man admitted with
AUR, TURP is indicated.
Would you do it on tmr’s list or wait til
he has TWOC successfully?
Any evidence?

228. 228
NPA : AUR patients
• ~50% had surgery during admission
(mean 6d post-admit) ~50% carry catheter
home (90% within 3m)
• More patients with IP TURP require
second surgery for bleeding (4.6 vs 1.7%)
• Less patients with IP TURP had postop
UTI (9.5 vs 15.6%)
• No difference in surgical outcome

229. 229
What are you going to do if you
found a stone in the bladder
during TURP?

230. 230
Bladder stone during TURP
• Stone is small , prostate big:
– Cystolithotirpsy  TURP
• Stone is big but can manage:
– Cystolithotripsy , TURP on a later date
• Stone is too large to deal with
endoscopically:
– Prostate is OK : TURP  open stone removal
– Prostate is big: open prostatectomy + stone
removal

231. 231
What are the results of WW as
compared with TURP?
Any head-to-head comparison?

232. 232
Wasson Cooperative study
• ~550 men with moderate symptoms randomised
to WW to TURP
• 5 yr results (Flanigan JU 1998) :
– Twice as many treatment failures in WW
– More patients improve and the degree of improvement greater
with TURP
– Best results with TURP are those with the highest bother
– WW group
• 24% crossover to TURP in 3 yr
• 36% crossover to TURP due to treatment failure in 5 yrs
– Those who cross-over has less degree of improvement in
SS, PVR and Qmx (40, 25 and 90%) than those who were
randomised to TURP right from the start, although the
improvement in bothersomeness was the same
– Similar rates of incontinence in both groups

233. 233
Who did the first open
prostatectomy and when?

234. 234
• Transvesical prostatectomy
– Commonly credited to Eugene Fuller in 1894
– (although reported already by McGill in 1887
in Leeds)
– Popularised by Sir Peter Freyer (1st reported
in 1900, 1000 patients reported in 1912)
• Retropubic prostatectomy
– Reported by Terence Millin in 1945 (20
patients)

235. 235
Open prostatectomy
• Indications:
– Large Prostate > 100gm
– TURP technically possible (limited hip abduction)
– Failed TURP (bleeding)
– Urethra too long
– Presence of bladder stone which are too large for
endoscopic means
• Contraindications:
– Small fibrous prostate
– Prior prostatectomy : obliteration of tissue plane
– Ca Prostate

236. 236
Suprapubic (Transvesical)
• Preferred for enlarged median lobe
• Bladder open
• Mucosa around protruding adenoma incised
• Plan btw adenoma and capsule developed
• Enucleation of adenoma
• Fr 22 foley , SP, retropubic drain
• Foley removed on day 3, spigot SP
• SP removed on day 6

237. 237
Simple retropubic (Millin)
• More precise anatomical exposure of the prostate
• Better visualization of prostate cavity
• More accurate removing of adenoma, control of bleeding
& division of urethra (incontinence)
• Not suitable for large median lobe (difficult to get behind)
• Low midline incision
• Ligation of DVC
• Transverse incision of prostate capsule
• Enucleation of adenoma
• Hemostasis
• Capsule closed, pelvic drain

238. 238
Are there any RCT comparing
TURP and open
prostatectomy?
What is the result?

239. 239
• No RCT comparing TURP vs OP
• Often “reckoned” retreatment rate after OP is
less than TURP
• Commonly quoted study in this area is Roos
study
• “Mortality and reoperation after open and
transurethral resection of the prostate for BPH”
– Roos et al NEJM 1989

240. 240
Roos
• Retrospective review of data of patients
undergoing open prostatectomy and
TURP in three regions : Manitoba Canada,
Oxford, UK and Denmark
• Total no. of prostatectomies > 50,000
• FU 8 yrs

241. 241
Roos
• Probability of needing a second
prostatectomy within 8 yrs higher after
TURP (12-15% vs 2-5%), irrespective of
geographical location
• Relative risk of dying (even long term)
after TURP 1.45 higher than after open
• Overall (TUR and open) highest risk of
death was from AMI

242. 242
Strengths
• Very large number of prostatectomies
studied
• Multicentred nature
• Comorbidities of the large number of
patients taken into account in analysing
the mortality

243. 243
Weakness
• Retrospective review
– Selection bias (open offered to those VERY fit)
• TURP techniques in 1963-85 have considerably
improved
• The use of 2nd
prostatectomy not a good
measure of the effectiveness of a procedure as
it may have been done for the wrong indication
(eg. no preop UDS)
• 8 yr mortality cannot really be ascribed to be due
to the operation itself

244. 244
What are minimal invasiveWhat are minimal invasive
alternatives to TURP?alternatives to TURP?

245. 245
1. TUNA
2. TUMT
3. TUIP
4. TURVP
5. TURis
6. Laser:
– PVP
– HoLAP, HoLRP, HoLEP

246. 246
TUNATUNA
• Transurethral radiofrequency
needle ablation
• Procedure:
– LA +/- IV sedation
– Low-level radiofrequency
– Transurethral needle delivery
system
– Heat  localized prostate
necrosis
• Result:
– Modest improvement of SS
– Not generally match the result
of TURP
– High long term retreatment
rate
• Complication:
– Bleeding (30%)
– UTI (10%)
– Urethral stricture (2%)
– ED (low)

247. 247
TUMT
• Transurethral microwave
thermotherapy
• Procedure:
– Microwave energy deliver
to prostate via intraurethral
catheter (with cooling
system)
– Heating and coagulative
necrosis
• Effect:
– Shrinkage of prostate
– Thermal damage of
neurons (heat –induced
adrenergic nerve block)
• Result: compare with
TURP [Ancona BJU
1998]
– SS improvement : 55% vs
75%
– Less sexual SE
– Longer catheterization
period
– More UTI & irritative
symptom
• EAU:
– Should be reserve for pt
who prefer to avoid surgery
but not responding to
medication

248. 248
What is the comparsion between
TURP VS TUIP?
• Ten RCT comparing TUIP to TURP are available
• Similar improvements of LUTS in patients with small
prostates (< 30 mL) and no middle lobe
• TUIP has several advantages
– Minimal risk of bleeding and blood transfusion
– Decreased risk of retrograde ejaculation
– shorter operating time
– Shorter hospital stay
– Yet a higher long-term failure rate
• Yang Q, and Abrams P et al. Transurethral incision compared with
transurethral resection of the prostate for bladder outlet obstruction: a
systematic review and meta-analysis of randomised controlled trials. J Urol
2001;165(5):1526-32
• TURP is the treatment of choice for prostates sized 30-
80mL

249. 249
TUVPTUVP
• Transurethral electrovaporization is an adaptation
of an old device, the roller ball electrode
• Vaporized and dessicated the prostate
• Compared to TURP, TUVP:
– Equivalent, short-term improvements in symptom
scores, urinary flow rate, and QoL
– Durable 5 yr result
– Decreased risk of TUR syndrome & blood transfusion
– Higher Rates of:
• Irritative voiding symptoms
• Dysuria and urinary retention,
• Need of unplanned secondary catheterization, appear to be
higher
• Reoperation rates

250. 250
TUVP: Which is true?
a. The current is pure cut T
b. The excursion need to be much slower T
c. Impedance independent (power maintained)
generator allowed more tissue removal
T
d. Dessication of tissue affect tissue removal
T
e. Bleeding and fluid absorption is less compared
to TURP T

251. 251
What is the improvement of
LUTS?
• All four surgical procedures (TURP, TUIP, TUVP and
open prostatectomy) result in an improvement of LUTS
90% for BOO, 60% without BOO, with open
prostatectomy leading to slightly superior results
• 10 RCTs comparing TURP to TUIP, both procedures
resulted in a similar improvement in symptoms after 12
months
• RCTs comparing TURP to TUVP also revealed similar
improvements of LUTS in both study arms
– Madersbacher S, et al. Is transurethral resection of the prostate still
justified? Br J Urol 1999;83(3):227-37.

252. 252
What is the improvement of
uroflowmetry?
• The mean increase of Qmax following
TURP is 115%
• TUVP, the Qmax increased by 155%
• The highest Qmax improvement (+175%)
is seen after open prostatectomy
– Madersbacher S, Marberger M. Is transurethral resection of the prostate
still justified? Br J Urol 1999;83(3):227-37.

253. 253
What is the improvement if post-
void residual volume?
• All four surgical procedures allow a
reduction of the post-void residual volume
of more than 50%
• -65% after open prostatectomy; -60% after
TUVP; -60% after TURP; and –55% after
TUIP
– Madersbacher S, Marberger M. Is transurethral resection of the prostate
still justified? Br J Urol 1999;83(3):227-37.

254. 254
What is the incontinence
rate?
• Stress incontinence ranges is 1.8%
following TUIP
• 2.2% following TURP
• Up to 10% following open prostatectomy
• Limited information on this issue is
available for TUVP; one RCT reported an
incontinence rate of 5%
• Madersbacher S, Marberger M. Is transurethral resection of the
prostate still justified? Br J Urol 1999;83(3):227-37.

255. 255
What is the risk of bladder neck
contracture and urethral stricture?
• Urethral stricture
– 2.6% after open prostatectomy
– 3.8% after TURP and 1.7% after TUIP
• The risk of bladder neck contracture is
– 1.8% after open surgery, 4% after TURP and 0,4%
after TUIP. The respective figures for TUVP are in the
range of TURP
• Madersbacher S, Marberger M. Is transurethral resection of
the prostate still justified? Br J Urol 1999;83(3):227-37.

256. 256
What is the risk of retrograde
ejaculation and erectile dysfunction?
• Retrograde ejaculation
– 80% after open prostatectomy
– 65-70% after TURP
– 40% after TUIP
• Erectile dysfunction
– TURP - 6.5%
– May be confounded by age
• Madersbacher S, Marberger M. Is transurethral
resection of the prostate still justified? Br J Urol
1999;83(3):227-37.

257. 257
Bipolar: TURis
• Transurethral resection in saline
• Patient does not form part of the electrical circuit
• Safer than conventional TURP
• Bipolar energy convert conductive medium into
plasma field of highly ionized particles (bubble
creation), which disrupt organic molecular bonds
between tissue, causing vaporization and
desiccation of tissue
• Early result are comparable
• No TUR syndrome

258. 258
How do we chose?
• Meta-analysis of 23 RCT : Ahyai [EU 2010]
• 2245 pt
• TURP vs others (TURis, TUVP, PVP , HoLEP)
• Result:
– statistically comparable efficacy and overall morbidity for MISTs
versus contemporary TURP
– Type, category (minor vs major), and the number of
complications (safety profile) vary specifically
– For bipolar TURP,further long-termdata are still warranted to
define its place in contemporary BPE management.
– For HoLEP, the next step is its broader clinical application
outside of experienced centres

259. 259
Laser assisted
prostatectomy

260. 260
What are the four types of
lasers used in prostate?
• Nd:YAG, Holmium:YAG, KTP:YAG and diode
• bare fibre, right-angle fibre or interstitial fibre
• The use of contact lasers using a bare fibre has
been abandoned
• Vaporization > 100oC, which cause the tissue to
be dehydrated, less tissue oedema
• Coagulation - little vaporization, achieve
permanent tissue damage. There is also
secondary tissue slough, associated with tissue
oedema

261. 261
“Greenlight” PVP?
• YAG laser light is shone through a KTP crystal, resulted in doubling
the frequency and halving wavelength to 532nm
• Strongly absorbed by both water irrigation and haemoglobin > good
prostate tissue vaporisation
• Poorly absorbed by saline, non-contact vaporisation is possible
• 80W/120W
• Rapid vaporisation with minimal coagulation of underlying structures
(<2 mm)
• Sweeping movement
• Indication:
– Symptomatic BPH
– Large prostate
– Pt on anticoagulant or antiplatelet [Sandhu JEU 2005]
• Disadvantage: No tissue

262. 262
PVP VS TURP
• Equivalent short/median term outcome (QOL/symptoms
scores/Qmax) and impact on sexual function (5yr)
• Less catheter time and hospital stay [Bachmann]
• Less risk of TUR syndrome
• Less risk of bleeding
• Less retrograde ejaculation (8%)
• Can be done as day case
• Insufficient long term data in terms of retreatment rate and urethral
stricture
Bouchier-Hayes et al BJUI 2010: April 105 964-968
• 120 randomised patients
• Equivalence in IPSS and Flow
• Benefits in Catheter time and LOS

263. 263
What is Holmium laser used in
prostate?
• Holmium laser: 2140nm
• Pulsed, solid-state laser
• Strongly absorbed by water
• Working distance - <0.5mm
• Zone of coagulation necrosis in tissue is
limited to 3-4 mm
• Sufficient to obtain adequate haemostasis
• Saline as irrigation , no TURS

264. 264
HoLAP (Ablation)
• Side-firing , Near-contact mode
• Vaporization of prostate
• 60W > 100W
• Symptoms improvement in long-term
– Tan AHH, et al. Long term results of high-power holmium laser vaporisation of
the prostate. BJU
• When compared with TURP
– Comparable result with shorter catheter time and
hospital stay
• Mottet, et al. Randomised comparsion of TURP VS Holmium laser
vaporisation for BPH. J Endourol
– Better for smaller glands

265. 265
HoLEP (enucleation)
• End-firing
• Cut groves into prostate down to capsule, dissected off and push into
bladder
• Morcellator – decreased the operation time (RISK !!!)
• Longer learning curve
• 2yr RCT : When compared with TURP > comparable result with shorter
catheter time and hospital stay [Wilson EU 2006]
• A recent RCT has shown that Holmium-laser enucleation leads to similar
outcome as open prostatectomy for men with large glands (> 100 mL) at a
significantly lower complication, e.g. less blood loss
– Kuntz RM, et al. Transurethral holmium laser enucleation versus
transvesical open enucleation for prostate adenoma greater than
100gm: a randomised prospective trial of 120 patients. J Urol
2002;168(4 Pt 1):1465-9.
• 3yr outcome: equivalent improvement of SS vs open prostatectomy [Kuntz
2006]
• 7yr outcome: sustained improvement in SS & flow rate [Urology 2005]

266. 266
HoLRP (resection)
• Mimic TURP
• Remove pieces of prostate down to
capsule
• Shorter cath time & hospital stay than
TURP
• Minimal post-operative dysuria
• Fallen out of favor

267. 267
AROU

268. 268
AROU
• Painful inability to void
• Relief pain after drainage of bladder by catheter
• 1st
cath: > 300-500ml , > 800 chronic retention
• Cause in men:
– Increase urethral resistance (BOO)
– Low bladder contractility
– Interruption of sensory and motor innervation
– Central failure of co-ordination of bladder contraction with
external sphincter relaxation (DSD)
• Association of AROU to mortality:
– After AROU , 2-3x higher mortality than population due to co-
morbidity

269. 269
Cause
• Men:
• BPE
• Ca Prostate
• Urethral stricture
• Prostate abscess
Women:
• Pelvic prolpase
• Urethral stricture
• Urethral diverticulum
• Post-surgery for
stress incontinence
• Pelvic mass (ovrian)
• Fowler’s syndrome

270. 270
AROU
• Spontaneous retention:
– More likely to recur : 50% in 1 week, 70% in 1
year
• Precipitated retention:
– Less likely to recur
– Anaesthetic
– Drug (anticholinergic, sympathomimetics)
– Abdominal or perineal surgery
– Immobility after surgery

271. 271
Management
• Urethral catheterization
• Measure volume, monitor UO
• Watch out for post-obstructive diuresis
• TWOC
• Need of surgery? Workup for co-
morbidities

272. 272
What are the predictor risk
factors for AUR?

273. 273
• Olmsted risk factors
– Age (70-70 8x c.f. 40-49)
– Baseline symptom score (7x moderate c.f.
mild)
– Qmx (<12 3x >12)
– Prostate vol (>30cc 3x <30cc)
– Large PVR (>50cc at baseline 3x <50cc)
Kolman et al J Urol 1999
– PSA (<1 : 7%, >7 : 14%)
PLESS, NEJM 1998

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What is the chance of a
successful void after the foley
taken off?
How can you improve that?

275. 275
• Previous studies on patients with AUR :
– Chance of successful TWOC after AUR 25-
40%
– McNeill, ALFAUR II, Urology 2005

276. 276
ALFAUR I
• 360 men 1st episode of spont AUR related
to BPH in multicentres
• Randomised to placebo and alfuzosin
once daily 10mg for 3 days
– 2 days before TWOC and 1 day after
• Primary outcome is whether can void (no
RU consideration)

277. 277
ALFAUR I
• 62% can void in alfu group
• 48% in placebo group
• Significantly different
• Predictors of failure of TWOC
– Age > 65, 1st cath vol > 1L
• Even with presence of these 2 factors, alfu
doubles the OR of successful TWOC

278. 278
ALFAUR II
• Those successfully wane off from foley
further randomised into (total 165)
– 6 months of placebo
– 6 months of alfuzosin
• Endpoint of study
– % Treatment failure (requirement of BPH
related surgery)
• Elective
• Emergent (AUR relapse)

279. 279
• Treatment failure requiring surgery
– 24% placebo and 17% alfu
• Most treatment failure was due to relapse of
AUR (emergent surgery)
• AUR relapse
– Alfu : 13.4% and Placebo : 19.3%
– Most events occurred within the 1st
3 months after the
1st
episode
– These relapses occurred earlier with placebo than
alfu

280. 280
• RR reduction of overall BPH related
surgery provided by alfu
– 1m : 62% (p=0.04)
– 3m : 52% (p=0.04)
– 6m : 29% (p=0.2)
• Factors affecting AUR relapse and BPH
related surgery
– High PSA
– High PVR

281. 281
Observations
• Although the 6m risk reduction of BPHRS
(~30%) is not stat. significant
– The benefit brought about by alfu is still
clinically significant
– After 1st AUR, alfu for 6 months
significantly reduces the need for surgery
– Alpha blockers may delay but they do not alter
BPH disease progression

282. 282
• ALFAUR study (McNeil 2004, 2005)
– Chance of successful void > 50%
– Alfuzosin increases the chance by 2x
– Predictors of TWOC being age >65 and 1st
cath > 1L
• 25% of these develop AUR again within next 6 months and
require surgery
– Predictors of relapse : high PSA and high postvoid residual after
the TWOC, DRE finding of large prostates
• Overall long term, this figures rises to 60%
– Success void chance increased to ~60% with Alfuzosin
• Reduces the risk of relapse by 50% at 3 months and 30% at
6 months
– Further 6/12 of alfuzosin temporarily reduces the risk of
BPHRS with reduction decreasing towards six months

283. 283
What is the postobstructive
diuresis?
• More than 200ml urine per hour X 2 consecutive hours
• Mechanism
– Physiological (fluid , waste product & electrolyte overload)
– Pathological, tubular dysfunction: decreased reabsorption of NaCl
– Increased ANP, decreased ADH
• After relief of the bilateral obstruction > tubular dysfunction
(20% creatinine clearance) recovered faster than glomerular
dysfunction (80% creatinine clearance)
• Treatment:
– Daily weight the patient
– Close monitoring of vitals & I/O, RFT/ K
– 50-90% fluid replacement of previous hour’s urine output
– Continue fluid support for 24-48 hour

284. 284
Who will fail after TWOC
• High retention volume
• Age
• Low detrussor pressure

285. 285
Mode to avoid surgery
• 5ARI
• Prostate stent
• Long term foley or SP
• CISC

286. 286
Nocturia
BJU review Jeffrey 2011

287. 287
Nocturia
• ICS: complain that an individual has to wake at
night one or more times to void
• Clinical relevance: > 2void/night likely to have
more consequence for the patient
• Why is nocturia important?
– Associated sleep framgnetation  induce health risk
– Reduce QOL, mood, producitvity at work
– Poorer overall health
– Increase fall and fracture

288. 288
• Prevalence:
– Men >70: 29-59%
– Women >70: 28-62%
– Overall: 58.5% Men > women
• Cause:
– Bladder storage problem
– Nocturnal polyuria
– 24hour polyuria
– Sleep disturbance
• Investigation:
– Detailed history, degree of border
– IPSS/QOL
– Urine analysis + C/ST , cytology if indicated
– Frequency Volume Chart !!!!!!

289. 289
Management
• Most important is to differentiated btw urgency
related nocturia and nocturnal polyuria
• Nocturnal Polyuria:
– Definition: nocturnal UO> 33% of total daily UO
– Cause:
• Congestive hearth failure
• OSA
• Peripheral edema and return of 3rd
space fluid at night during
recumbent position
• Excessive evening fluid intake
• Circadian defect in section of AVP
• Primary pituiatary disorder

290. 290
Nocturia and OAB
• Most pt with nocturia do not have OAB
• Most pt with OAB do have nocturia
• Antimuscarinic do not appear to eb
efficacious for nocturia
• Antimuscarinic may be effect for nocturnal
void due to urgency

291. 291
Management
• Lifestyle modification:
– Pre-emptive voiding
– Nocturnal dehydration
– Dietary and fluid restriction (caffeinated, alcohol)
– Medication timing (diuretics in mid-afternoon)
– Evening leg elevation to mobolize fluids
– Use of sleep medication / aid
– Use of protective undergarments
• Plant extracts: did not show any efficacy
• Non-antidiuretic medication:
– AARB  no use
– 5ARI  no use
– Antimuscarinic:
• Tolterodine & fesoterodine
• Effective only for nocturnal void associated with severe urgency
• Unable to decrease number of nocturnal void

292. 292
Antidiuretic therapy
• Aim: to reduce nocturnal urine volume
• Indication: pt with nocturnal polyuria
• MOA:
– Desmopressin (synthetic analogue of AVP)
– Selective V2 receptor agonist (no HT)
– Increase reabsorption of water in distal and collecting tubules
– Concentrate urine , decrease UO postpone need to void
• Grade A recommendation from International consultation on
incontinence
• Med: 0.1, 0.2. 0.4mg PO (tablet , oral lyophilisate melt)
• Result: Placebo RCT , 3 weeks
– 34% with clinical response (>50% reduction of nocturnal void) vs 3%
– Reduce mean number of void : 3.0  1.7
– Long term efficacy : 10-12m
• Adverse effect:
– Hypo Na (related to Age, not for pt > 65yo)
– Require monitoring of Na level

293. 293

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295. 295

296. 296

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299. 299

300. 300