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1
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%
10-Year CumulativeProbability Freedom from
Prostate Enlargement
PSA < 1.7 PSA > 1.7
83% 27%
10-Year CumulativeProbability Freedom from
Prostate Enlargement
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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Abstract #1090 at AUA 2001Acute Urinary Retention: What is the
Impact on Quality of Life?
• 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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Abstract #1090 at AUA 2001Acute Urinary Retention: What is the
Impact on Quality of Life?
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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Abstract #1090 at AUA 2001Acute Urinary Retention: What is the
Impact on Quality of Life?
• 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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Abstract #1090 at AUA 2001Acute Urinary Retention: What is the
Impact on Quality of Life?
• 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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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