benign prostatic hypertrophy hyperplasia enlargement

Benign ProstaticBenign ProstaticHypertrophyHypertrophy HyperplasiaHyperplasiaEnlargementEnlargement

BPHBPHBenign Prostatic HyperplasiaBenign Prostatic Hyperplasia MicroscopicMicroscopic

Proliferation of Proliferation of stromalstromal (fibromuscular) and (fibromuscular) and epithelialepithelial (prostate secretory glands) in the transitional zone(prostate secretory glands) in the transitional zone

MacroscopicMacroscopic “ “Enlarged Prostate”; DRE, TRUS, CT, MRIEnlarged Prostate”; DRE, TRUS, CT, MRI

Static (epithelial/having a large blockage)Static (epithelial/having a large blockage)

Dynamic (increased “tone” of muscle fibers)Dynamic (increased “tone” of muscle fibers) ClinicalClinical

LUTS: storage vs. voiding vs. both (nonspecific)LUTS: storage vs. voiding vs. both (nonspecific)

BPHBPH

By the numbers:By the numbers: 14 million US men 14 million US men

(not all seek medical attention)(not all seek medical attention) Annual cost of $4 billion per yearAnnual cost of $4 billion per year

BPHBPH

Incidence and EpidemiologyIncidence and Epidemiology Most common benign tumor in menMost common benign tumor in men PrevalencePrevalence

20% in men 41-5020% in men 41-50

50% in men 51-6050% in men 51-60

Increase by 10% per 10 yearsIncrease by 10% per 10 years Familial component likelyFamilial component likely Higher incidence in higher income & higher educationHigher incidence in higher income & higher education Metabolic syndrome increases likelihood of BPHMetabolic syndrome increases likelihood of BPH

AnatomyAnatomy

BPHBPH

Evaluation:Evaluation: International Prostate Symptoms Score International Prostate Symptoms Score

(IPSS)/AUA Symptoms Index:(IPSS)/AUA Symptoms Index:0-35 points for symptoms and severity0-35 points for symptoms and severity

LUTS:LUTS: 0-7 Mild0-7 Mild 8-18 Moderate8-18 Moderate >18 Severe>18 Severe

BPHBPHTreatment Options:Treatment Options: 1. Watchful waiting1. Watchful waiting 2. Phytotherapeutics2. Phytotherapeutics 3. Medical management3. Medical management

Alpha blockersAlpha blockers

5 Alpha reductase inhibitors (5 ARI’s)5 Alpha reductase inhibitors (5 ARI’s)

Phosphodiesterase inhibitors (PDE5i)Phosphodiesterase inhibitors (PDE5i)

Combination therapyCombination therapy 4. Minimally invasive techniques4. Minimally invasive techniques 5. Surgical techniques5. Surgical techniques

Watchful WaitingWatchful Waiting

Decrease PM fluidsDecrease PM fluids

Decrease caffeine/ETOH/bladder irritants Decrease caffeine/ETOH/bladder irritants

Timed voids/double voidsTimed voids/double voids

Review Rx list and optimizeReview Rx list and optimize

Treat constipationTreat constipation

PhytotherapyPhytotherapy

Phytotherapeutic agents are standardized Phytotherapeutic agents are standardized herbal preparations consisting of complex herbal preparations consisting of complex mixtures of one or more plants which mixtures of one or more plants which contain as active ingredients plant parts or contain as active ingredients plant parts or plant material in the crude or processed plant material in the crude or processed state.state.

Last year, the US herbal supplement Last year, the US herbal supplement market was $7.4 billion.market was $7.4 billion.


Phytotherapeutic agents are commonly Phytotherapeutic agents are commonly prescribed in Europe for LUTS, and in the prescribed in Europe for LUTS, and in the US 30-90% of patients seen by urologists US 30-90% of patients seen by urologists for BPH/LUTS may be taking themfor BPH/LUTS may be taking them

The US market for dietary supplements to The US market for dietary supplements to treat LUTS or just “to keep the prostate treat LUTS or just “to keep the prostate healthy” is around $1.5 billion per yearhealthy” is around $1.5 billion per year


Product VariabilityProduct Variability Evaluation and use of these products are Evaluation and use of these products are

complicated by variations in the plants complicated by variations in the plants themselves as well as the process to extract themselves as well as the process to extract the desired components.the desired components.

Study (Feifer et al., 2002), showed that 3/6 Study (Feifer et al., 2002), showed that 3/6 samples of saw palmetto was less than 20% samples of saw palmetto was less than 20% of the amount stated on the label and two of of the amount stated on the label and two of these had less than 5%these had less than 5%

PhytotherapyPhytotherapyMajor Issues with phytotherapy:Major Issues with phytotherapy: 1. The clinical benefits of phytotherapeutic agents for 1. The clinical benefits of phytotherapeutic agents for

BPH are still uncertainBPH are still uncertain 2. Saw Palmetto is the most widely used nutraceutical 2. Saw Palmetto is the most widely used nutraceutical

for BPHfor BPH 3. The mechanism of action of phytotherapeutic agents 3. The mechanism of action of phytotherapeutic agents

on BPH are thought to be weakly similar to finasteride, on BPH are thought to be weakly similar to finasteride, decreasing testosterone’s effects on the prostatedecreasing testosterone’s effects on the prostate

4. There is significant interbrand and intrabrand 4. There is significant interbrand and intrabrand variabilityvariability

5. The “presumed” safety of these products has never 5. The “presumed” safety of these products has never been fully confirmedbeen fully confirmed

Rare scientific head to head comparisons with Rare scientific head to head comparisons with standard treatmentsstandard treatments

Phytotherapy

Saw PalmettoAfrican PlumSouth African Star GrassStinging NettleRye-Pollen ExtractPumpkin SeedsOther: Soy, Grape Juice, Cactus Flower, Zinc, Selenium

Alpha-BlockersBasis of therapy: The dynamic (increased muscle tone) part of BPH

A component of BPH and bladder obstruction is mediated by alpha adrenergic receptors associated with prostatic smooth muscle.

Alpha-BlockersClassification

Nonselective:Phenoxybenzamine 10mg BID

Alpha-1Terazosin (Hytrin) 5 or 10mg qDayDoxazosin (Cardura) 4 or 8mg qDayAlfuzosin (Uroxatral) 10mg qDay

Alpha-1a Subtype SelectiveTamsulosin (Flomax) 0.4mg qDaySilodosin (Rapaflo) 8mg qDay

Alpha-Blockers

Typical Side Effects: Orthostatic Hypotension Dizziness Tiredness Retrograde Ejaculation Rhinitis Headache Floppy Iris Syndrome

5 Alpha Reductase Inhibitors5 Alpha Reductase Inhibitors

DevelopmentDevelopment Experimental studies:Experimental studies:

Testosterone production or function is inhibited in Testosterone production or function is inhibited in men castrated before pubertymen castrated before puberty

These same men were noted to have abnormal These same men were noted to have abnormal prostate developmentprostate development

Later determined that embryonic development of Later determined that embryonic development of the prostate is dependent on the androgen DHT, the prostate is dependent on the androgen DHT, which is converted from testosterone by the which is converted from testosterone by the enzyme, 5 alpha reductase.enzyme, 5 alpha reductase.


DHTDHT Provides the major growth stimulus for Provides the major growth stimulus for

prostatic tissue due to its 4-5 fold higher prostatic tissue due to its 4-5 fold higher affinity for the prostatic androgen receptor affinity for the prostatic androgen receptor compared to testosteronecompared to testosterone

Other anti-androgenic agents have been Other anti-androgenic agents have been investigated, but most lead to decreased investigated, but most lead to decreased levels of testosterone as well as DHT levels of testosterone as well as DHT

(think Lupron in prostate cancer)(think Lupron in prostate cancer)


Low testosterone (abnormal testosterone Low testosterone (abnormal testosterone to estradiol ratios)to estradiol ratios) Intolerable sexual side effects: erectile Intolerable sexual side effects: erectile

dysfunction, decreased libidodysfunction, decreased libido Also: gynecomastia and hot flashesAlso: gynecomastia and hot flashes

Thus, the development of 5 ARI’s to Thus, the development of 5 ARI’s to improve LUTS without sexual side effects improve LUTS without sexual side effects associated with reduction in testosterone associated with reduction in testosterone levelslevels


Side Effects:Side Effects: ImpotenceImpotence Decreased libidoDecreased libido Decreased ejacualteDecreased ejacualte Breast enlargementBreast enlargement Hot flashesHot flashes


Finasteride (Proscar)Finasteride (Proscar) Results in 80-90% reduction of type II 5 alpha Results in 80-90% reduction of type II 5 alpha

reductase within the prostate.reductase within the prostate. Decreased intraprostatic DHT there is reduction of Decreased intraprostatic DHT there is reduction of

epithelial (static) glandular tissue volume with epithelial (static) glandular tissue volume with resultant decrease in total gland volume (resultant decrease in total gland volume (~20-30%)~20-30%)

Note finasteride (static) vs Flomax (dynamic)Note finasteride (static) vs Flomax (dynamic)


Development of dutasteride (Avodart)Development of dutasteride (Avodart) Hypothesis that inhibition of both Type I & Hypothesis that inhibition of both Type I &

Type II 5 alpha reductase may increase Type II 5 alpha reductase may increase efficacy of tx of BPHefficacy of tx of BPH

Thus, dutasteride (second generation) that Thus, dutasteride (second generation) that inhibits both typesinhibits both types

In comparison to finasteride, it suppresses In comparison to finasteride, it suppresses DHT production by 93% (finasteride 70%, but DHT production by 93% (finasteride 70%, but objective and subjective urinary tract effects objective and subjective urinary tract effects are the same.are the same.


Prostate Cancer Prevention Trial (PCPT)Prostate Cancer Prevention Trial (PCPT) Results:Results:

Prostate cancer was detected in 24.4% of controls Prostate cancer was detected in 24.4% of controls and only 18.4% of treated patientsand only 18.4% of treated patientsFirst time a treatment was shown to prevent or First time a treatment was shown to prevent or delay the appearance of prostate cancerdelay the appearance of prostate cancerHowever, also noted that the proportion of Gleason However, also noted that the proportion of Gleason 7 or higher tumors was greater in the finasteride 7 or higher tumors was greater in the finasteride group.group.


REDUCE TrialREDUCE Trial Chemoprevention for prostate cancerChemoprevention for prostate cancer 8,200 men8,200 men 4 year trial4 year trial Double-blind placeboDouble-blind placebo 23% reduction in risk of prostate cancer23% reduction in risk of prostate cancer No increased risk of aggressive tumors like No increased risk of aggressive tumors like

PCPT.PCPT.

Combination Therapy

Veteran’s Affairs Cooperative Study 1996 Placebo, Finasteride, Terazosin, and Combo 1229 patients, Double Blind Placebo Controlled Showed significant improvement in AUA symptom

scores in terazosin and combo therapy groups. Since they had similar improvements, it was

determined that the finasteride had no benefit Thus, alpha blockade (Flomax) had superiority over

finasteride at 1 year.

Combination Therapy

Medical Therapy of Prostatic Symptoms (2001) Can medical therapy prevent or delay the

progression of BPH in the long term. 5 years out: Combination of Doxazosin and

Finasteride exerts a clinically relevant, positive effect on rates of disease progression.

Combination Therapy

Combination of Dutasteride and Tamsulosin (2003) by Barker et. al.

Combo for 24 weeks, then withdrew the Tamsulosin for 12 weeks.

Patients with IPSS score <20: 84% continued monotherapy without worsening of symptoms

IPSS scores >20: 42% had worsening of symptoms Concluded that combo therapy allows alpha blockers

to provide more rapid relief and 5 alpha reductase inhibitors for long-term treatment.

Start with combo, patients with less severe symptoms can stop alpha blocker; more severe continue combo

Phosphodiesterase 5 InhibitorsPhosphodiesterase 5 InhibitorsCialis 5mg dailyCialis 5mg daily

Decreases the smooth muscle tone in the Decreases the smooth muscle tone in the bladder, prostate and urethra (like Flomax)bladder, prostate and urethra (like Flomax)

SE include back/muscle aches, GERD, SE include back/muscle aches, GERD, and headaches and strengthening of and headaches and strengthening of erections.erections.

Good combination RxGood combination Rx

Nice for ED, not for the patient-physician-Nice for ED, not for the patient-physician-insurance company relationshipinsurance company relationship

Minimally Invasive Therapy

Transurethral Microwave Procedures Microwaves are sent through a catheter to at

least 111 degrees Cooling system protects the urinary tract Outpatient Reduces: frequency, urgency, straining, and

intermittent flow Does NOT correct incomplete emptying Long term effects are still unknown

Minimally Invasive Therapy

Transurethral Needle Ablation (TUNA) Low-level radiofrequency energy through twin

needles to burn away selected areas of the prostate

Shields protect the urethra Improves urine flow and relieves symptoms

Conventional Surgical Therapy

Indications for surgery Urinary retention from BPH, medical refractory Gross hematuria from BPH Bladder stones UTI’s Renal Insufficiency/hydronephrosis


Transurethral Resection of the Prostate (TURP) “Gold Standard” 60-90 minutes General or Spinal Wire Loop Complications: Infertility, UTI, Bladder stones, gross

hematuria, retrograde ejaculation, urethral strictures or bladder neck contractures.

Transurethral Incision of the Prostate (TUIP)

Transurethral Incision of the Prostate (TUIP)

Variation of TURP Instead of removing

prostate tissue, small cuts are made in bladder neck

Shorter operative time Good for short glands, men

who have had radiation therapy and are at risk for incontinence or wish to preserve fertility

Transurethral Laser Surgery

Transurethral Laser Surgery

Usually a side-firing laser is placed through cystoscope

Holmium, Greenlight/PVP, Thullium

Laser destroys/vaporizes prostatic tissue

As good as a TURP with similar potential complications


Surgical “Open” Prostatectomy

In cases where the prostate is too large for a TURP or if the bladder has very large stones

Open incision or with DaVinci Robot

Opens the prostatic capsule and scoops out the prostatic tissue

Other treatments

UroLume urethral stent Migration, worsening irritative symptoms Encrustation and prostatic ingrowth

Intraprostatic ethanol and Botox injections Performed via transrectal ultrasound

SummaryDiagnosis

Subjective and Objective findings

Medical Treatment

Indications for surgery

Types of Surgery

Questions?

benign prostatic hypertrophy hyperplasia enlargement

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