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Benign Prostate DisordersBenign Prostate Disorders

Frank P. Begun, M.D.Associate Professor, Urology

Medical Director Urological Services at OSUMedical Director, Urological Services at OSU East Hospital

The Ohio State University

Objectives/GoalsObjectives/GoalsTo understand the causes of BPHT i th t l t d tTo review the symptoms related to BPHTo gain knowledge of the different forms of treatment for bladder outlet obstruction due to BPHobstruction due to BPH

Medical managementSurgical optionsOther treatments

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ObjectivesObjectivesTo review the causes andTo review the causes and symptoms of prostatitisTo understand the diagnosis and management of prostatitis and Pelvic Pain Syndrome

Benign Prostate DisordersBenign Prostate Disorders

Benign Prostatic Hyperplasia (BPH)ProstatitisPelvic Pain Syndrome (PPS)

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EpidemiologyBPH/BPEBPH/BPE

EtiologySymptomsObjective DataNonsurgical/Medical ManagementSurgical Management

BPHBPHExact molecular etiology is unknownunknownAndrogens and estrogensGrowth factorsCell-cell interactionsImpaired programmed cell death (apoptosis)Neurotransmitters

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BPHRole of Androgens

BPHRole of Androgens

Post natal androgen surges are criticalg gImprinting of prostate cellsAffects maturation process and cell deathNecessary during puberty and agingNecessary during puberty and aging Prostatic levels of dihydrotestosterone (DHT) and androgen receptors play a key role

BPH Role of Androgens

BPH Role of Androgens

Prostate retains ability to respond to androgens throughout ones lifeConcentration of androgens does not increase with ageStromal cell – 5 alpha reductase Type 2 p ypinteraction seems to be key event in the development of BPHRole of estrogens is unclear

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BPHBPHStromal events induce glandularStromal events induce glandular proliferationInteraction between growth factors, GF receptors, and steroid hormonesProgrammed cell death/apoptosis

From: Campbell-Walsh Urology, 9th editionFrom: Campbell-Walsh Urology, 9th edition

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BPHOther Factors

BPHOther Factors

Inheritable component: earlier ponset, larger gland size, autosomal dominant Sympathetic nerve pathwaysInflammationInflammationRefluxEnvironmental

Pathophysiology of Obstruction

Pathophysiology of Obstruction

BPH develops in the Transition and Periurethral Zones : central prostateProstate Cancer develops in the Peripheral Zone : posterior prostateStatic component of obstructionDynamic component of obstruction

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BPHBPHObstructive uropathy/Urinary obstructionobstructionBladder outlet obstruction (BOO)Lower Urinary Tract Sx (LUTS)Prostatism

BPH ≠ Urinary obstructionUrinary obstruction ≠ BPH

BPEBPE

E l ti f i d th lExplanation of increased urethral resistance due to BPE is too simplisticMust factor in age related detrussor and bladder neck dysfunctionStatic and dynamic factors

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From: Campbell-Walsh Urology, 9th editionFrom: Campbell-Walsh Urology, 9th edition

Size Doesn’t MatterSize Doesn’t MatterNot critical when deciding whether or gnot to RxNot well correlated with Sx severity, degree of obstruction, or Rx outcomeImportant wrt deciding mode of Rxp gHowever, size does correlate with disease progression and risk of acute retention

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BPHBPHMicroscopic BPH: stromal and epithelial cellular proliferationMacroscopic BPH: increase in the size of the prostate as a result of microscopic BPH (BPE)Clinical BPH: signs and Sx of obstruction due to BPE (LUTS, BOO, Prostatism)

Clinical Manifestations of BPH

Clinical Manifestations of BPH

HematuriaMicroscopicGrossLUTSUTIUTIUrinary retentionHydronephrosisRenal Insufficiency

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EvaluationEvaluationHistoryAUA/IPSS Symptom ScoreAUA/IPSS Symptom ScoreDREUrinalysis (r/o UTI)Uroflow and Post Void Residual (PVR)(PVR)Imaging : Transrectal U/S (TRUS) with volume measurementUrodynamic Testing

International Prostate Symptom Score (IPSS)

International Prostate Symptom Score (IPSS)

7 questions + QOL assessment7 questions QOL assessmentConsidered “Gold Standard”Not intended to establish the Dx of BPEInitial assessment of severity of SxDeterminant of Rx responseDeterminant of Sx progression

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IPSSIPSS0-7 Mild Sx8-19 Moderate Sx20-35 Severe SxDegree of “bothersomeness”Need to consider patient’s lifestyle, performance status

UroflowUroflowNon invasiveInaccurate for voided volumes <150mLMax flow rate (Qmax)No definite cutoff as a determinant for RxNo age or voided volume adjustmentLow flow does not differentiate BOO from detrussor hypocontractility

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Post Void Residual (PVR)Post Void Residual (PVR)

High intra-individual variabilityHigh intra individual variabilityPoor correlation with other signs and SxMeasured by U/S or catheterization? P di t f R t? Predictor of Rx outcomeIncreasing PVRs may be an indicator of the need for intervention

CystoscopyCystoscopyNot indicated to determine the need for treatmentPoor correlation between visual appearance and treatment outcomeIndicated to determine the mostIndicated to determine the most appropriate type of treatment for those who have opted for surgical management

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Surgical Rx: IndicationsSurgical Rx: IndicationsPatient preferencepRecurrent urinary retentionRecurrent UTI’s Recurrent gross hematuriaBladder calculusLarge bladder diverticulaRenal insufficiency due to BPE

Medical ManagementMedical Management

Preferred treatment for those menPreferred treatment for those men lacking absolute indications for surgical intervention.US Medicare Database:

250,000 prostate surgeries in 1987116,000 in 1996

88,000 in 2000

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Urinary ObstructionUrinary ObstructionSt ti C tStatic Component: BPH/mechanical obstructionDynamic Component: smooth muscle function at bladder outlet

Nonsurgical Management of BPH

Nonsurgical Management of BPH

Alpha Adrenergic BlockersAlpha Adrenergic BlockersAndrogen Suppression/AblationCombination TherapyAromatase InhibitorsAromatase InhibitorsPhytotherapy

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Alpha Adrenergic Receptors

Alpha Adrenergic Receptors

From: Campbell-Walsh Urology, 9th edition

Alpha Blocker TherapyAlpha Blocker TherapySelective α1 Adrenergic receptorSelective α1 Adrenergic receptor blockadeSeveral medications available:

Doxazosin (Cardura)Terazosin (Hytrin)Tamsulosin (Flomax)Alfuzosin (Uroxatrol)

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Alpha Blocker TherapySide Effects

Alpha Blocker TherapySide Effects

DizzinessOrthostatic hypotensionFatigue/somnolenceHeadacheRhinitisNauseaRetrograde ejaculation

Androgen AblationAndrogen AblationAgents causing a loss of Testosterone or DHT action result in aTestosterone or DHT action result in a decrease in the volume of the prostate.Primarily an epithelial regression.Maximum results occur within 6Maximum results occur within 6 monthsTreats static component of BPH5 alpha reductase inhibitors

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Androgen AblationAndrogen Ablation5 alpha reductase converts T DHTDHT is predominant intraprostatic androgenFinasteride (Proscar) Type 1Finasteride (Proscar) Type 1Dutasteride (Avodart) Type 1 and 2~30% volume reduction

From: Campbell-Walsh Urology, 9th editionFrom: Campbell-Walsh Urology, 9th edition

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Androgen AblationAndrogen AblationDecreased risk of urinary retentionDecreased risk of urinary retentionDecreased need for prostate surgeryVolume reduction of prostateCan lower PSA – effect on cancer detectionSide effects : impotence

Combination TherapyCombination TherapyTheory: synergistic effects ofTheory: synergistic effects of alpha blocker and antiandrogenTreats both components of prostate obstruction: static and pdynamicVA Coop Study

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PhytotherapyPhytotherapySerenoa repens Saw palmetto berrySabal serrulata American dwarf palmSabal serrulata American dwarf palmHypoxis rooperi South African star grassPygeum africanum African plum treeUrtica dioica Stinging nettleSecale cereale Rye pollenCucurbita pepo Pumpkin seedOpuntia Cactus flowerPinus Pine flowerPicea Spruce

PhytotherapyDosages of Common Phytotherapeutic

Preparations

PhytotherapyDosages of Common Phytotherapeutic

Preparations

Serenoa repens (Permixon)160 mg bid Pygeum africanum (Tadenan)50 mg bid Secale cereale (Cernilton)6 capsules β-Sitosterol (Harzol)20 mg tid β-Sitosterol (Azuprostat)65 mg tid

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PhytotherapyPhytotherapyLittle is know about active compoundsLittle is know about dosageLittle is know about mechanism of actionPaucity of double blinded prospective comparative studiesAlmost all data is anecdotal.

Surgical Treatment Options

Surgical Treatment Options

Intraprostatic StentspTransurethral Needle Ablation (TUNA)Transurethral Microwave (TUMT)Transurethral Laser TherapyTURP : Gold StandardTURP : Gold StandardTransurethral Incision (TUIP)Transurethral VaporizationOpen Prostatectomy

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Intraprostatic StentsIntraprostatic StentsPrimary indication is in patientsPrimary indication is in patients who are unfit for surgeryTemporary vs. PermanentComplications: migration, painMay be useful as a temporary measure after Laser Rx or TUMT

TUNATUNAHeats prostate tissue to >60°CHeats prostate tissue to >60 CUses radiofrequency (RF) energyResults in deep tissue necrosisSpares the prostatic urethraDoesn’t require anesthesia, therefore, office procedure

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TUNATUNA

From: Campbell-Walsh Urology, 9th edition

Transurethral Laser Therapy

Transurethral Laser Therapy

G li ht LGreenlight Laser

Holmium Laser (HoLEP)

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TURPTURP

From: Campbell-Walsh Urology, 9th edition

Transurethral VaporizationTransurethral Vaporization

Principle similar to TURPRemoval of central prostate tissue

fNo specimen for path analysisLess blood loss

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Benign Prostate Disorders

Benign Prostate Disorders

ProstatitisChronic Pelvic Pain Syndrome (CPPS)Syndrome (CPPS)

ProstatitisProstatitisMost common GU Dx in men <50 yrs old3rd most common GU Dx in men >50 yrs

(BPH, prostate cancer)2-10% of men have prostatitis-like Sx2-10% of men have prostatitis-like Sx9-16% have had the Dx of prostatitisAccounts for 3-12% of male GU office visits

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ProstatitisClassification

ProstatitisClassification

Acute BacterialChronic BacterialNon-bacterialP d iProstatodynia

Prostatitis ClassificationNIH System

Prostatitis ClassificationNIH System

Category I : Acute bacterialCategory I : Acute bacterialCategory II : Chronic bacterialCategory III : Chronic Pelvic Pain Syndrome (CPPS)

IIIA : Inflammatory CPPSIIIB : Non-inflammatory CPPS

Category IV : Asymptomatic

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Bacterial ProstatitisBacterial ProstatitisG S fGold Standard for Dx is the Meares Stamey “4 Glass” collection technique1st described in 1968Can use pre and post massage “2 Glass” collection

Acute Bacterial Prostatitis/UTIAcute Bacterial Prostatitis/UTI

E coli accounts for 65-80% of infectionsP d Kl b i ll S tiPseudomonas, Klebsiella, Serratia, Enterobacter account for another 10-15%Enterococci 5-10%

Urovirulence : p-fimbri, biofilmsReflux of urine into the intraprostatic ducts

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Bacterial ProstatitisEtiologies

Bacterial ProstatitisEtiologies

UTITransurethral surgeryIndwelling catheterDysfunctional voiding/neurogenic bladderbladderPhimosisAltered host immune response Idiopathic

ProstatitisOther Organisms

ProstatitisOther Organisms

CorynebacteriumChlamydiaUreaplasmaCandidaTrichamonas

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Bacterial Prostatitis TreatmentBacterial Prostatitis TreatmentMost antibiotics achieve poor intraprostaticconcentrations and yet antibiotics are the mainstay of treatment Fluoroquinolones Trimethoprim-sulfaMacrolides : erythromycin, azithromycinTetracycline/doxycyclineNo standard treatment durations

Chronic Bacterial ProstatitisTreatment

Chronic Bacterial ProstatitisTreatment

Duration of optimal Rx is unknownDuration of optimal Rx is unknownSulfa-trimethoprim remains primary agent30-50% efficacy ratesFl oroq inolones also sef lFluoroquinolones also useful1 month vs. 3 month RxDifferential Dx = CPPS

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CPPSCPPSAbsence of bacteria in prostatic secretionssecretionsCommon presenting Sx is painPerineal, suprapubic, penileCan also be groin, testicular, low backPain during and after ejaculation (50%)Irritative or obstructive voiding Sx

CPPSCPPS

>3 months Sx = CPPSSx tend to wax and waneUp to 33% will resolve over 1 year’s timeyear s time

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CPPSCPPSIntraductile reflux

Chemical prostatitisImmunological AlterationsNeurologicalPelvic floor muscle dysfunctionPsychological factors

CPPS TreatmentCPPS Treatment40% achieve benefit from antibiotic RxRxLong duration Rx not recommendedAlpha blocker RxAnti-inflammatory RxBiofeedbackBiofeedbackPelvic muscle relaxationAntidepressantsPsych