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

ZONAL ANATOMY OF THE PROSTATE

BPH

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.

Epidemiology of Benign Prostatic Hyperplasia 50% of men by age 50 yrs 90% of men by age 80 yrs 4

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!

Major Risk Factors for BPH Increasing Age Normal Androgen Levels (Functioning Testes) * McConnell, JD. Urol Clin N Amer, 1990.

Prostate Physiology

Normal Prostate vs. Prostate Hyperplasia Coffey and Griffiths

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

Prostate Growth With Age

Prostate Size and Advancing Age Relationship 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

Impact Of Size Progression With Age 45 years 60 years 75 Years IPSS = 15 IPSS = 3 IPSS = 13 20 ml 30 ml 42 ml 2.5% Increase/year IPSS =23 IPSS = 13 IPSS = 3 20 ml 42 ml 90 ml 5.0% Increase/year Andersen, Nickel et al, 1997

The Definitions of Benign Prostatic Hyperplasia Symptomatology Histology Prostate Volume Peak Flow Rates Pressure Flow Variables Post-void Residuals Quality of Life Quantitations Combinations of these 2

Definition of BPH HISTOLOGIC

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

Definition of BPH SYMPTOMATIC No Obstruction Varying degrees of bother

Clinical Manifestations of BPH *In the majority of men symptoms are:

Diagnosis of BPH A thorough History is essential! Make sure voiding sx’s are from BPH

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

Diagnosis of BPH PSA 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

Diagnosis of BPH

BPH Treatment Guidelines Need to Assess Symptoms and Size Clinical Decision Symptom Score 0 - 7 Watchful Waiting Treatment 8 - 35

Evaluation and Treatment Algorithm

Acute Urinary Retention and Surgical Intervention Risk Factors SYMPTOMS PROSTATE SIZE AGE

Acute Urinary Retention or Surgery Who’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

Abstract #1085 at AUA 2001 PSA Predicts the Long-Term Risk of Prostate Enlargement: Results from the Baltimore Longitudinal Study of Aging Age 40-49 Age 50-59 Age 60-69 20-Year Cumulative Probability Freedom from Prostate Enlargement 10-Year Cumulative Probability Freedom from Prostate Enlargement 10-Year Cumulative Probability Freedom from Prostate Enlargement *Wright et al

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

Abstract #1090 at AUA 2001 Acute 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

Abstract #1090 at AUA 2001 Acute 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

Abstract #1090 at AUA 2001 Acute Urinary Retention: What is the Impact on Quality of Life? mo 2 mo 3 mo 6 mo Admission Within 72 hrs Worst HRQoL Some Improvement But HRQoL score remained low during the 6-month follow up *Kirby et al

Abstract #1090 at AUA 2001 Acute 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

Abstract #1090 at AUA 2001 Acute 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

Treatment Alternatives for BPH Medical Therapy Surgery Minimally Invasive Watchful Waiting

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

Alpha Blocker Therapy

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

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

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

Prostate Physiology

5 ARI’s Mechanism of Action

5 ARI Mechanism of Action

CYSTOSCOPIC VIEW of BPH

TURP

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

HoTURP Essentially an enucleation of prostate

TUEVP Edges of grooves have highest current density.

TUMT Different size catheters. Takes a while for channel creation

TUNA® 2 twin needles at 90o, not seen, act as thermal electrodes with insulating sheath to protect urethra.

Sonablate™ (HIFU)

Minimally Invasive Techniques for the Treatment of BPH

Phytotherapy in the Treatment of BPH

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

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

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