Etiology and Pathophysiology Of BPH

Dr Ahmed Eliwa MBBCh, MSc urology

Assistant lecturer in urology and andrology

• What are the factors responsible for prostaticgrowth and enlargements

• What's the relation between BPH bladderobstruction

• What's the bladder response to obstruction

• How can these approach of treatment

• BPH is a pathologic process that contributesto, but is not the sole cause of, lower urinarytract symptoms (LUTS) in aging men.

underlying etiology of prostatic growth in older men, cause-and-effect relationships have not

been established.

• The ideas clinical symptoms of BPH(prostatism) are simply due to a mass-relatedincrease in urethral resistance are toosimplistic.

• significant portion of LUTS is due to

age-related detrusor dysfunction and otherconditions such as polyuria, sleep disorders,and a variety of systemic medical conditionsunrelated to the prostate-bladder unit.

• This has led to the recognition that, althoughLUTS commonly may be related to bladderoutlet obstruction (BOO) as a result of benignprostatic obstruction (BPO), which is oftenassociated with benign prostatic enlargement(BPE) resulting from the histologic condition ofBPH, this is not invariably the case.

From Roehrborn CG. Pathology of benign prostatic hyperplasia. Int JImpot Res 2008;20[Suppl. 3]:S11–8.)

• Failure to empty can be related to an outletobstruction or to detrusor under-activity ofthe bladder or to a combination of both.

(Reynard et al, 1996).

ETIOLOGY

• Histopathologically BPH is characterized byan increased number of epithelial andstromal cells in the periurethral area of theprostate and thus correctly referred to ashyperplasia and not hypertrophy

• The precise molecular etiology of thishyperplastic process is uncertain.

• Androgens

• Estrogens

• Apoptosis

• Stromal-epithelial interactions

• Growth factors

• Neurotransmitters

may play a role, either singly or in combination,in the etiology of the hyperplastic process.

ROLE OF ANDROGENS

• Although androgens do not cause BPH, thedevelopment of BPH requires the presence oftesticular androgens during prostatedevelopment, puberty, and aging(McConnell,1995; Marcelli and Cunningham,1999)

• In the Olmsted County cohort theestradiol/bioavailable testosterone ratioincreased (Roberts et al, 2004).

• In the prostate the nuclear membrane boundenzyme steroid 5α-reductase converts thehormone testosterone into DHT, the principalandrogen in this tissue (McConnell, 1995)

90%Testicular

10%Adrenal

Prostatic Androgen

• Inside the cell, both testosterone and DHTbind to the same high-affinity androgenreceptor protein (Chatterjee, 2003).

• androgen withdrawal leads to the activationof specific genes involved in programmed celldeath (Kyprianou and Isaacs, 1989;Martikainen et al, 1990).

ANDROGEN RECEPTORS

• The prostate, unlike other androgen-dependent organs, maintains its ability torespond to androgens throughout life.

Two types of steroid 5α-reductase have beendiscovered, each encoded by a separate gene(Russell and Wilson, 1994).

• Type 1 5α-reductase

• Type 2

• Clearly, the type 2 isoform is critical tonormal development of the prostate andhyperplastic growth later in life.

• ROLE OF ESTROGENS

• experimental BPH, estrogen appears to beinvolved in induction of the AR (Moore et al,1979).

• Estrogen may, in fact, “sensitize” the aging dogprostate to the effects of androgen (Barrackand Berry, 1987).

• estrogen treatment stimulates the stroma,causing an increase in the total amount ofcollagen (Berry et al, 1986a, 1986b)

• ER-α is expressed by prostate stromal cells,and ER-β is expressed by prostate epithelialcells (Prins et al, 1998).

• From experimental studies with aromataseinhibitors it appears that decreases inintraprostatic estrogen in animal models maylead to reduction in drug-induced stromalhyperplasia (Farnsworth, 1996, 1999).

REGULATION OF PROGRAMMED CELLDEATH

• due to epithelial and stromal proliferation orto impaired programmed cell death leadingto cellular accumulation.

Increased expression of antiapoptotic pathway genes(e.g., BCL2) supports this

hypothesis (Kyprianou et al, 1996; Colombel et al, 1998)

• Androgens not only are required for normalcell proliferation and differentiation in theprostate but also actively inhibit cell death(Isaacs, 1984).

• Neural signaling pathways, especially α-adrenergic pathways, may also play a role inbalancing cell death and cell proliferation(Anglin et al, 2002)

• Tenniswood (1992) suggested androgensproviding a modulating influence over thelocal production of growth regulatory factorsthat varies in different parts of the gland.

• Members of the transforming growth factor-β(TGF-β) family are likely candidates for thisregulatory step (Martikainen et al, 1990).

STROMAL-EPITHELIAL INTERACTION

• BPH may be due to a defect in a stromalcomponent that normally inhibits cellproliferation, resulting in loss of a normal“braking” mechanism for proliferation.

• The process of new gland formation in thehyperplastic prostate suggests a“reawakening” of embryonic processes inwhich the underlying prostatic stromainduces epithelial cell development (McNeal,1990).

• signaling protein CYR61

GROWTH FACTORS

growth stimulatory factors such as the

• FGF-1

• FGF-2

• FGF-7

• FGF-17 families

• vascular endothelial growth factor (VEGF), andinsulin-like growth factor (IGF) may play a role,with DHT augmenting or modulating the growthfactor effects.

• FGF-7 is the leading candidate for the factormediating the stromal cell–based hormonalregulation of the prostatic epithelium.

• FGF-7local ischemia

• A transgenic mouse line Int-2/FGF-3

androgen-sensitive epithelialhyperplasia in the male mouseprostate histologically similar tohuman and canine BPH (Tutroneet al, 1993).

OTHER SIGNALING PATHWAYS

• sympathetic pathways may be important in thepathogenesis of the hyperplastic growth process(McVary et al, 1994, 2005).

• α-Adrenergic blockade, in some model systems,can induce apoptosis (Anglin et al, 2002).

• α-Adrenergic pathways can also modulate thesmooth muscle cell phenotype in the prostate(Lin et al, 2000).

• Renin-angiotensin system (RAS) are present inprostatic tissue and may be activated in BPH(Dinh et al, 2001, 2002; Fabiani et al, 2001).

• Either with or without sympatheticmodulation, local RAS pathways maycontribute to cell proliferation and smoothmuscle contraction.

• POTENTIAL ROLE OFINFLAMMATORY PATHWAYS ANDCYTOKINES IN BENIGN PROSTATICHYPERPLASIA

• IL-2, IL-4, IL-7, IL-17, interferon-γ (IFN-γ), andtheir relevant receptors are found in BPHtissue (Kramer et al, 2002; Steiner et al,2003a, 2003b).

• IL-2, IL-7, and IFN-γ stimulate the proliferationof prostatic stromal cells in vitro.

• Prostatic epithelial cell senescence results inincreased expression of IL-8, which canpromote proliferation of nonsenescentepithelial and stromal cells (Castro et al, 2004}

• An excellent recent review of BPH as apotentially autoimmune disease waspublished by Kramer and colleagues (2007),and illustrates the immunologic key featuresof chronic inflammation in BPH and thepresent interpretation of these changes in thedevelopment and progression of BPH.

• To date, however, no firm cause-and-effectrelationships have been established betweenprostatic inflammation and related cytokinepathways and stromal-epithelial hyperplasia.

GENETIC AND FAMILIAL FACTORS

• autosomal dominant

• 50% of men undergoing prostatectomy forBPH when younger than 60 years of age

• 9% of men undergoing prostatectomy forBPH when older than 60 years

DNA mutations (White et al, 1990)

DNA hypomethylation (Bedford and van Helden, 1987)

abnormalities of nuclear matrix protein expression (Partin et al, 1993)

miscellaneous genetic polymorphisms (Werely et al, 1996;

Konishi et al, 1997; Habuchi et al, 2000)

Abnormal expression of the Wilms tumor gene (WT1) (Dong et

al, 1997)

specific gene or genes involved infamilial BPH or that contribute to the risk

of significant prostaticenlargement in sporadic disease

PATHOPHYSIOLOGY

Prostatic hyperplasia

increases urethral resistance, resulting in compensatory changes in

bladder function.

elevated detrusor pressure required to maintain urinary flow in the presence of increased outflow resistance occurs at the expense of normal bladder storage function.

Obstruction-induced changes in detrusor function,

compounded by

age related changes in both bladder and nervous system function

lead to urinary frequency, urgency, and nocturia, the most bothersome BPH-related complaints

• Prostatic smooth muscle represents asignificant volume of the gland (Shapiro et al,1992)

• Active smooth muscle tone in the humanprostate is regulated by the adrenergicnervous system (Roehrbornand Schwinn,2004).

• Receptor binding studies clearly demonstratethat α1A is the most abundantadrenoreceptor subtype present in thehuman prostate (Lepor et al, 1993a, 1993b;Price et al, 1993).

• α1A receptor clearly mediates active tensionin human prostatic smooth muscle

• type 4 and type 5 phosphodiesteraseisoenzymes in the prostate and the detrusormuscle of the bladder implies thatphosphodiesterase inhibitors may beappropriate candidate therapies for BPH-related LUTS (Uckert et al, 2001, 2008, 2009).

• kallikrein-kinin system (e.g., bradykinin) mayplay a role in the regulation of both smoothmuscle proliferation and contraction in theprostate (Walden et al, 1999; Srinivasan et al,2004).

The Bladder’s Response to Obstruction

• obstruction-induced changes in bladderfunction rather than to outflow obstructiondirectly.

•

• Approximately one third of men continue tohave significant voiding dysfunction andmostly storage symptoms after surgical reliefof obstruction (Abrams et al, 1979).

Obstruction-induced changes

detrusor instability or decreased compliance

are clinically associatedwith symptoms of frequency urgency.

decreased detrusor contractility

associated withdeterioration in the force of the urinary stream,HesitancyIntermittencyincreased residual urinedetrusor failure.

smooth muscle hypertrophy

significant intracellular and extracellular changes in thesmooth muscle cell that lead to detrusor instability andin some cases impaired contractility.

• changes in smooth muscle cell contractile proteinexpression,

• impaired energy production (mitochondrialdysfunction)

• calcium signaling abnormalities

• impaired cell-to-cell communication

increased intravesical pressure and maintained flow

(Levin et al, 1995, 2000).

Skeletal muscle

hypertrophy

Maintain power and function

ADAPTIVE RESPONSE

Detrusor

muscle

change in myosin heavychain isoform expression(Linand McConnell, 1994;Cher et al, 1996)

significant alteration

in the expression of a variety of thin filament-associated

proteins (Mannikarottu et al, 2005a, 2005b, 2006).

stress stresssmooth muscle cells revert to a secretoryphenotype in response to obstruction-inducedhypertrophy.

One consequence of this phenotypic switch isincreased ECM production.

The detrusor smooth muscle cell is a keycontributor to the complex of symptomsassociated with prostatic obstruction.

(Christ and Liebert, 2005).

• that obstruction may modulate neural-detrusor responses as well (Steers et al, 1990,1999; Clemow et al, 1998, 2000).

• Altered neural control of micturition has beennoted in aging rats, including reduced bladdercontractility, impaired central processing, andaltered sensation (Chai et al, 2000).

INSIGHTS FOR THE TREATMENT

Prostatic hyperplasia

Prostatic smooth muscle contraction

Detrusor response to obstruction

Prostatic Hyperplasia

Aromatase inhibitors

Prostatic smooth muscle contraction

Detrusor response to obstruction

EASY WAY

Terminology

• Benign Prostatic Enlargement• BPE

• Clinical Dx

• Benign Prostatic Hyperplasia• BPH

• Pathological Dx

• Bladder Outflow Obstruction• BOO

• Urodynamic Dx

LUTS and BOO

• 1/3 of men with LUTS do not have BOO

• 5% - 35% of patients with BPH & LUTS do notimprove symptoms after TURP

• LUTS have a poor diagnostic specificity forBOO

• Prostate size and uroflowmetry have bettercorrelation with urodynamic study thansymptoms alone

Diagram showing the relationship between histologic hyperplasia of the prostate (BPH), lower urinary tract symptoms (LUTS), benign

prostate enlargement (BPE), and bladder outlet obstruction (BOO). The size of the circles does notrepresent actual proportions but

rather illustrates the partial overlap between the different disease definitions. (From Roehrborn CG. Pathology of benign prostatic

hyperplasia. Int J Impot Res 2008;20[Suppl. 3]:S11–8.)

Prostate Pyramid

Urologist

GP

Lives with symptoms

Asymptomatic

Treatment of BPH

• Treating an enlarged prostate ?

• Treating lower urinary tract symptoms?

• Treating bladder outlet obstruction?

• Can LUTS disappear after treatment?

• Can BOO be relieved after treatment?

• Any complication may occur?

• Is the treatment cost- effective ?

Therapeutic modalities for LUTS ascribed to the prostate

• Watchful waiting and fluid restriction, naturalhistory of BPO may wax and wan

• Medical treatment to reduce prostate size ordecrease intraprostatic resistance

• Surgical treatment to remove prostaticobstruction or reduce urethral resistance

• Minimally invasive therapies

Do I Need an Operation ?

• History (IPSS)ssssssss

• DRE• U/S Scan - KUB

- TRUS• Uroflow Test

Minimally Invasive and Endoscopic Management ofBenign Prostatic Hyperplasia• Intraprostatic Stents• Transurethral Needle Ablation of the Prostate• Transurethral Microwave Therapy• Lasers• Transurethral Resection of the Prostate• Transurethral Vaporization of the Prostate• Transurethral Incision of the Prostate• Other Technologies

Retropubic and Suprapubic Open Prostatectomy

• Indications for Open Prostatectomy

• Preoperative Evaluation

• Operating Day Preparation

• Surgical Technique

• Postoperative Management

• Complications

• Acute Urinary Retention

Surgery in BPH

Indicated in : Severe symptoms and advanced cases

Acute retention of urine

Refractory urinary retention

Persistent hematuria

Complications like hydronephrosis

Trans-Urethral Resection of Prostate

OTHER TECHNIQUES

Balloon Dilatation

Intra Prostatic Stents

Tuna

Lasers

Electro Vaporization

Vapour Resection

TRANS URETHRAL NEEDLE

ABLATION OF PROSTATE

LASERS

Holmium

Green Light PVP

Diode Laser

• ELECTRO VAPOURIZATION

• VAPOUR RESECTION

Trans Urethral Microwave of Prostate

How Advancing Technology Change Us !!!

Prostate Resectoscope and TURP

Complications of TUR-Prostate

• Peri-operative bleeding• Urinary tract infection and urosepsis• Electrolyte imbalance, hemolysis, acute

tubular necrosis• Acute pulmonary edema• Bladder neck or urethral contracture• Retrograde ejaculation and erectile

dysfunction• Urge or stress urinary incontinence

Minimally invasive procedure

• Transurethral vaporization- resection of prostate(TUVRP)

• Ho-YAG laser coagulation of prostate• Visual laser ablation of prostate (VLAP)• Transurethral needle ablation (TUNA)• High intensity focused ultrasound (HIFU)• Microwave hyperthermia• Minimally invasive = minimally effective?• A higher re-treatment rate than TURP although less

complication occurs

Intra-Prostatic Stent

Interstitial Laser Coagulation

Hyperthermia of BPH

Surgical Management

Indications-• upper tract dilation,

• renal insufficiency secondary to BPH, or

• If the prostate gland is greater than 80 to 100 g,an open prostatectomy should be performed)

• The standard endoscopic procedure for BPH is atransurethral resection (TUR) of the prostate

Acute urinary retention Gross hematuriaFrequent UTIVesical stone BPH related hydronephrosis or renal function deterioration

Conventional Surgical Therapy

• Transurethral resection of the prostate (TURP)

• Open simple prostatectomy

106

TURP

• “Gold standard” of surgical treatment for BPH

• 80~90% obstructive symptom improved

• 30% irritative symptom improved

• Low mortality rate 0.2%

107

The “gold standard”- TURP

Benefits

Widely available

Effective

Long lasting

Disadvantages

Greater risk of side effects andcomplications

1-4 days hospital stay

1-3 days catheter

4-6 week recovery

108

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%)

109

TUR syndrome

• TUR is performed with a non-hemolytic fluidsuch as 1.5% glycine (not Saline)

• TUR syndrome may develop from the resultinghypervolemia and dilutional hyponatremia.

• Patients with TUR syndrome may experiencehypertension, bradycardia, nausea, vomiting,visual disturbance, mental status changes, andeven seizures.

• Occurs in approximately 2% of patients

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),

111

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

112

Destroy prostate tissue with heat

Tissue is left in the body and is expelled overtime (called sloughing)

Transurethral Microwave Therapy (TUMT)

Transurethral Needle Ablation (TUNA®)

Interstitial Laser Coagulation (ILC)

Water Induced Thermotherapy (WIT)

heat therapies

n

n

n

n

n

n

heat therapiesBenefits

Office treatments

Local anesthesia

Minimally invasive

Reduced risk ofcomplications ascompared toinvasive surgical“TURP”

Disadvantages

Some symptoms willpersist for up to 3 months

Cannot predict who willrespond

May require prolongedcatheterization

n

n

n

n

n

n

n

possible side effects of

Urinary Tract Infection

Impotence

Incontinence

heat therapies

n

n

n

surgical treatment

TURP

“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

(transurethral resection of the prostate)

n

n

n

the “gold standard”- TURP

Benefits

Widely available

Effective

Long lasting

Disadvantages

Greater risk of side effectsand complications

1-4 days hospital stay

1-3 days catheter

4-6 week recovery

n

n

n

n

n

n

n

possible side effects of

Impotence

Incontinence

Bleeding

Electrolyte imbalance (TUR Syndrome)

May result in ICU (Intensive Care Unit)

TURP

n

n

n

n

n

TURP : Start

TURP : Middle

TURP : Finish

TURP : Catheter

Side Effects

• Retrograde Ejaculation

• Erectile dysfunction

• TUR syndrome

• Redo rate

• Death

68 %

31 %

5-10%

0.5 %

1 % per year

0.2 %

Conclusions• B.P.E. is a common condition with many more men suffering symptoms

than present to the medical profession.

• Signs and symptoms vary in their character and severity.

• All patients should have standard assessment in the form of history,examination and investigations with specialised investigations beingreserved for complicated or equivocal cases.

• Medical and surgical treatment options are available and these should bediscussed with the patient prior to commencement.

• Surgery remains the gold standard in the form of TURP

Principles of Thermotherapy

• Blood supply of BPH adenoma more fragilethan prostate capsule

• Adenoma can be heated to cause necrosis

• Capsule protected by better blood flow

• Tissue necrosis, nerve damage/destructionlead to improved voiding symptoms

Anatomy of BPHNormal BPH

Hypertrophied

detrusor muscle

Obstructed

urinary flow

PROSTATE

BLADDER

URETHRA

Roehrborn CG, McConnell JD. In: Walsh PC et al, eds. Campbell’s Urology. 8th ed. Philadelphia, Pa: Saunders; 2002:1297-1336.

Radio Frequency Generator

•Monitors temperature of urethra and prostate 50 times per second with Precision Reassurance Technology

•Computerized graphics allow physician to view treatment in real time

Cartridge and Needle Deployment

Disposable Cartridge and Reusable Handle

Dual Deployment of Needles and Shields

Schematic of TUNA Procedure

Creation of a LesionCompleted Procedure

with 8 Lesions

Transurethral Microwave Therapy

• Microwave energy causes tissue necrosis

• Cooling channels in catheter cool urethra

Transurethral Microwave Therapy

Interstitial Laser Therapy

• Lesions created throughout prostate

• Laser fiber alignment critical

• Median lobe can be treated

Interstitial Laser Coagulation

Anesthesia Options

• Local (lidocaine jelly)

• Oral narcotics

• Prostate block

• I.V. sedation

Treatment Results After Thermotherapy

• Most patients see improvement in symptoms

• Results not as consistent as TURP

• Bladder function important

• Long term results of TUNA, TUMT and ILT aresimilar

TURP (Rotor Rooter)

Transurethral ElectrodesTransurethral Electrodes

The TURP

TURP

“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

(transurethral resection of the prostate)

n

n

n

TURP• “Gold standard” of surgical treatment for BPH

• 80~90% obstructive symptom improved

• 30% irritative symptom improved

• Low mortality rate 0.2%

The “gold standard”- TURP

Benefits

Widely available

Effective

Long lasting

Disadvantages

Greater risk of side effectsand complications

1-4 days hospital stay

1-3 days catheter

4-6 week recovery

n

n

n

n

n

n

n

Laser Prostatectomy

1. PVP

2. Thulium

3. Diode

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

Laser Wavelengths

ABSORPTION vs. WAVELENGTH

980nm is 2300 times more absorbed in H2O than 532nm

532nm is 74 times more absorbed in HbO2 than 980nm

200W

120W70W

Optical Penetration Depth

KTP532 nm

Diode830 nm

Nd:YAG1064 nm

Ho:YAG2100 nm

CO2

10 m

Tissue

0.8 mm

5 mm

10 mm

0.4 mm 0.02 mm

Diode 980nm RevoLix

Laser ablation - VLAP

• Visual laser ablation of the prostate

• Side-firing laser – Nd:YAG

• Non-contact technique

• Large volume tissue coagulation

• Coaguative necrosis with delayed healing, with tissue slough

• Contact technique – vaporisation

• LA + iv sedation

ILC-Intersitial laser coagulation

• Creation of intraprostatic coagulative by laser light at low power

• Cystoscopy + direct introduction of laser through urethral mucosa

• Diode laser

Holmium laser prostatectomy

• Ho:YAG: excellent for incisional prostectomy

• HoLEP: Retrograde enucleation of prostate

• HoLRP: Retrograde excision of hyper plastic tissue

• Relatively slow procedure with a steep learning curve

PVP Laser Prostatectomy

• Vaporizes tissue

• Minimal bleeding

• No catheter post-op

Uses a very high powered green laser and a thin,flexible fiber

Fiber is inserted into

the urethra through a

cystoscope

How does PVP work?

n

n

Quickly and precisely vaporizes and

removes the enlarged prostate tissue

The green laser energy is hemostatic, so

there is almost no bleeding

How does PVP work?

n

n

Pre Op Immediate Post Op

3 Months Post Op

PVP Laser Removes Tissue

• Opens bladder neck

• Cavity similar to TURP

• Improvement in symptoms similar to TURP

• Less impotence than TURP, other morbidity similar

Mean Peak Flow Rate (ml/s)

7.8

27.3 26.2

23.3 23.4

0

5

10

15

20

25

30

pre-op 1 year 2 years 3 years 5 years

pre-op1 year2 years3 years5 years

Malek et al., Mayo Clinic, Durability Study

Green Light PVP

Post Void Residual (ml.)

154

44 3851

21 26

0

20

40

60

80

100

120

140

160

Pre-op 3 mos 6 mos 12 mos 24 mos 36 mos

post-void

Malek et al., Mayo Clinic, Durability Study

Green Light PVP

AUA Semptom Skoru

22.0

3.9 3.6 3.62.9

0.0

5.0

10.0

15.0

20.0

25.0

pre-op 1 year 2 years 3 years 5 years

AUA symptomscore

Malek et al., Mayo Clinic, Durability Study

Green Light PVP