1 BPH Bruce B. Sloane, MD FACS Drexel University College of Medicine.

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BPH

Bruce B. Sloane, MD FACS

Drexel University College of Medicine

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ZONAL ANATOMY OF THE PROSTATE

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BPH

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Benign Prostatic Hyperplasia

• Afflicts many men

• Interferes with normal activities

• Reduces sense of well-being

• Progresses in many men

* N Engl J Med 1998; 338: 557-563.

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Epidemiology of Benign Prostatic Hyperplasia

• 50% of men by age 50 yrs

• 90% of men by age 80 yrs

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Epidemiology of BPH

• 17 Million Men Afflicted

• Only Half Diagnosed

• -1/3 Receive Treatment

• - 2/3 Watchful Waiting/Surveillence

• 88% Choose Pharmacologic Therapy (Alpha Blockers and 5-alpha reductase inhibitors

• Direct Costs of BPH > $1 Billion Annually!

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Major Risk Factors for BPH

• Increasing Age

• Normal Androgen Levels (Functioning Testes)

* McConnell, JD. Urol Clin N Amer, 1990.

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Prostate Physiology

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Normal Prostate vs. Prostate Hyperplasia

Coffey and Griffiths

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Current Basic Science Research on BPH

• Histopathology Strongly Implicates Local Paracrine and Autocrine Growth Factors and Inflamatory Cytokines in Pathogenesis of BPH

• Growth Regulatory Proteins (members of fibroblast, insulin-like and tranforming growth factor, interleukins) are overexpressed in BPH

• A Landscape of Increased Stromal and Epithelial Growth and Mesenchymal Transdifferentiation Leads to Progression

• Inflammation may contribute to tissue injury and drive local Growth Factor Production

• New Treatments aimed at these Pathways may emerge

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Prostate Growth With Age

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Prostate Size and Advancing AgeRelationship to Progression

• Prostate growth in population-based studies – 0.7 to 1.5 mL/yr over 4 years

• Prostate growth in BPH clinical study– 1.8 mL/yr over 4 years

*J Urol 132:474-479, 1984*J Urol 152(5 Pt 1):1501-1505, 1994*JAMA 270:860-864, 1993*Br J Urol 75:347-353, 1995*NEJM 338(6), 2/26/98

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Impact Of Size Progression With Age

2.5% Increase/year2.5% Increase/year

5.0% Increase/year5.0% Increase/year

45 years

IPSS = 3

20 ml

20 ml

30 ml 42 ml

42 ml 90 ml

60 yearsIPSS = 13

IPSS = 13

IPSS = 15

IPSS =23

Andersen, Nickel et al, 1997

75 Years

IPSS = 3

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The Definitions of Benign Prostatic Hyperplasia

Histology SymptomatologyProstate Volume

Peak Flow Rates Pressure Flow Variables

Post-void ResidualsQuality of Life Quantitations

Combinations of these

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Definition of BPH

• HISTOLOGIC

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Definition of BPH

OBSTRUCTIVE

• Bladder Outlet Obstruction

• Increasing Residual Urine leading to Urinary Retention

• Recurrent Urinary Tract Infections

• Pathologic Changes in Bladder Structure and Function

• Hydronephosis/Renal Failure

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Definition of BPH

• SYMPTOMATIC

• No Obstruction

• Varying degrees of bother

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Clinical Manifestations of BPH

Obstructive Irritative Hesitancy Frequency Weak Stream Urgency Incomplete Voiding Urge Incontinence Straining to Void Nocturia Prolonged Micturition Dysuria Overflow Incontinence Postvoid Dribbling

*In the majority of men symptoms are:

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Diagnosis of BPH

• A thorough History is essential!

• Make sure voiding sx’s are from BPH

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Other Causes of Voiding Symptoms

• Diabetes, Parkinson’s, Stroke, Spinal Cord Injury, Multiple Sclerosis, Transverse Myelitis, Dementia, Urethral Stricture, Radical Pelvic Surgery

• Medications: Anticholinergics, Alpha Agonists, Analgesics

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Diagnosis of BPH• Medical history and Physical examination• Symptom score

– Bother score

• Urinary flow rate +/- Urodynamic Studies• Post Void Residual Measurement• Histology during biopsy, surgery, or autopsy

• PSA

*Urology vol 58, no 6A, Suppl, Dec 2001

Initial Evaluation for BPH

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Diagnosis of BPH

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BPH Treatment GuidelinesNeed to Assess Symptoms and Size

0 - 7

8 - 35

Watchful Waiting

Treatment

Symptom Score Clinical Decision

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Evaluation and Treatment Algorithm

Acute Urinary Retention and Surgical Intervention

Risk Factors

AGE

SYMPTOMS

PROSTATESIZE

Acute Urinary Retention or SurgeryWho’s at risk?

• AGE– Men in their 50s have 3 times the risk as men in their 40s– Men in their 70s have 8 times the risk as men in their 40s

• SYMPTOMS– Men with moderate to severe symptoms have 3 times the risk as men with

mild symptoms

• PROSTATE SIZE– Men with larger prostates are at 3 times greater risk

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Abstract #1085 at AUA 2001PSA Predicts the Long-Term Risk of Prostate

Enlargement: Results from the Baltimore Longitudinal Study of Aging

PSA < .30 PSA > .30

89% 63%

20-Year CumulativeProbability Freedom from

Prostate Enlargement

PSA < .80 PSA > .80

90% 59%



PSA < 1.7 PSA > 1.7

83% 27%



Age 40-49 Age 50-59 Age 60-69

*Wright et al

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Risk Factors for BPH Progession

• Advance Age• Increased Total Prostatic Volume• Elevated PSA• Higher AUA Symptom Index• Increased Bother• Decreased Peak Urinary Flow Rate• Rising Post Void Residual• Obesity• Chronic Prostatic Inflammation

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Abstract #1090 at AUA 2001Acute Urinary Retention: What is the

Impact on Quality of Life?

• Introduction: – Acute urinary retention (AUR) is the most common

urological emergency.

• Objective:– To assess the impact of admission for AUR on

patients’ health related quality of life (HRQoL)

*Kirby et al

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• Methods:– Consecutive male patients over 50 years old admitted

to emergency room with AUR– Self completion questionnaire administered

• HRQoL (general health, daily living activities, anxiety, pain, urological symptoms)

• 5 time points (within 72 hrs, 1, 2, 3, and 6 months)

*Kirby et al

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Admission Within72 hrs

1mo

2mo

3mo

6mo

WorstHRQoL

SomeImprovement But HRQoL score remained low

during the 6-month follow up

*Kirby et al

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• Results:– Mean HRQoL were lowest at admission– There was a modest improvement after discharge– HRQoL remained low during the 6-month follow up

*Kirby et al

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• Conclusions:– This study is the first to show that AUR appears to

have a significant and persistent impact upon patients in terms of their HRQoL.

– Further preventative measures may be justified to avoid episodes of AUR and its adverse effect on patients’ quality of life.

*Kirby et al

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Treatment Alternatives for BPH

Medical TherapyMedical Therapy SurgerySurgery

Minimally InvasiveMinimally Invasive Watchful WaitingWatchful Waiting

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Alpha Blockade in BPH• Reduce the sympathetic tone of the prostate

• Contraction of smooth muscle is predominantly mediated by alpha 1 (1A and 1D) receptors

• Many of the side effects appear to be caused by alpha 2 receptors

• Extraprostatic factors may be involved in symptoms of storage and voiding

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Alpha Blocker Therapy

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Alpha Blockade in BPH

• There are no significant differences in efficacy among all alpha blockers

• However, there are differences in the adverse events associated with their use.– Alfuzosin and Tamsulosin appear to have fewer

adverse events associated with their use.

*Urology vol 58, no 6A, Suppl, Dec 2001

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Treatment of BPH – Alpha Blockers

• Medical Therapy with Alpha Blockers is mainstay of treatment

• Several different Alpha Blockers available: Terazosin, Doxazosin, Tamsulosin, Alfuzosin

• Tamsulosin and Alfuzosin = “prostate specific” – work on alpha 1a receptors

• All have equal efficacy• Used in combination with 5 Alpha Reductase inhibitors

in certain patients

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5 Alpha Reductase Inhibitors

• Mechanism of action = Reduces intraprostatic DHT levels

• Results in reduction in prostate size• Lowers PSA• Finasteride shown to decrease risk of Prostate Cancer by

22%• Reduces risk of urinary retention and need for surgery in

some men (prostate size > 30 gms, PSA>1.2)• May interfere with natural history of progressive BPH• MTOPS Study generated above data

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Prostate Physiology

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5 ARI’s Mechanism of Action

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5 ARI Mechanism of Action

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CYSTOSCOPIC VIEW of BPH

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TURP

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Minimally Invasive Treatments for BPH~~~~~~~~~~

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HoTURP

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TUEVP

http://www.circoncorp.com/products/gyne/gynetrends/gt_v1_n1/wn_n_gt_b2.jpg

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TUMT

http://www.urolog.nl/menu/tumt2.jpg

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TUNA®

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Sonablate™ (HIFU)

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Minimally Invasive Techniques for the Treatment of BPH

Technique Description

TVP Electrosurgical vaporization + coagulation

TUNA Tissue necrosis by deliveringradiofrequency energy through needles

TUMT Heat energy within the prostate lobeswhile cooling the urethral mucosa

VLAP Quartz laser fiber that deflects anNd:YAG laser beam at a right angle intothe parenchyma of prostate

ILC Laser creates an intraprostatic coagulativelesion

TUEA Enzymatic solubilization to reversestromal rigidity

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Phytotherapy in the Treatment of BPH

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Phytotherapeutic Agents� The most frequently used plant extracts are:

• bark of Pygeum africanum

• pollen extract

• leaves of trembling poplar

• root of Hypoxis rooperi

• seeds of Cucurbita pepo

• fruit of Serenoa repens (Sabal serrulata)

• roots of Echinacea purpura

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Phytotherapeutic Agents

� some patients like the idea of “natural” treatments

� few placebo-controlled studies

� no long-term data on side effects

� no standardization in product formulations

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BPH: Conclusion

• BPH has a high prevalence among the aging male population

• There are varying definitions of BPH – Symptomatic, Obstructive, Histologic

• It is often (but not always) a progressive condition• Medical Treatment ( Alpha Blockers) is the Mainstay of

Therapy• Be aware of other conditions which cause voiding sx’s in

men• Minimally invasive procedures are available

1 BPH Bruce B. Sloane, MD FACS Drexel University College of Medicine.

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Transcript of 1 BPH Bruce B. Sloane, MD FACS Drexel University College of Medicine.