19 - Benign Prostatic Hyperplasia | Smiths General Urology, Seventeenth Edition (LANGE Clinical Medicine)

Authors: Macfarlane, Michael T.

Title: Urology, 4th Edition

> Table of Contents > Part Two - Selected Topics > Chapter 19 - Benign Prostatic Hyperplasia

Chapter 19

Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is characterized by progressive enlargement of the prostate gland resulting in bladder outlet obstruction and increasingly difficult voiding. It is a disease of the elderly, rarely affecting males younger than age 40. The mean age at which patients develop symptoms is between 60 and 65 years.

Pathogenesis

The prostate consists of three distinct zones: an outer peripheral zone, a central zone, and a periurethral transition zone. BPH develops in the transition zone, whereas prostate cancer usually arises in the peripheral zone. Clinically, the prostate is still often considered to have five lobes: anterior, posterior, median, and two lateral lobes.

The cause of BPH remains unclear; however, its relationship to aging and the testes is well documented. Most current theories on the etiology of BPH focus on an increased sensitivity to androgens and a decreased rate of cell death. Direct stromal-epithelial interaction under hormonal control appears to be essential to the process.

Prostate growth and development are under the influence of the male hormone, testosterone, and its more active metabolite dihydrotestosterone (DHT). Testosterone, which is produced primarily by the testes under control of the hypothalamic-pituitary axis, is converted to DHT by the enzyme 5- -reductase. DHT is the major intracellular androgen and is believed to be responsible for the maintenance of BPH. With advancing age, Leydig cell testosterone production decreases, resulting in a relative excess of estrogens. Estrogens have been demonstrated to cause increased nuclear accumulation of DHT receptors and to result in a net increased formation of DHT within the prostate. DHT stimulation results in increased production of epidermal growth factor (EGF), whereas other factors cause a reduction in programmed cell death or apoptosis, presumably as a result of transforming growth factor- (TGF- ). BPH is believed to result from the imbalance of stromal and epithelial hyperplasia caused by EGF in the face of reduced apoptosis caused by TGF- .

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Pathophysiology

Prostatic hyperplasia would be of no importance were it not for the consequent bladder outlet obstruction. The pathophysiology of bladder outlet obstruction has three components: a mechanical component, a dynamic component, and the detrusor response.

Mechanical Obstruction

With progressive prostatic growth, patients will present clinically with lateral and/or median lobe enlargement. As prostatic enlargement encroaches on the urethra, urinary outflow obstruction occurs. The mechanical component of obstruction is a direct result of this enlarging mass of tissue and its ability to increase outlet resistance and obstruct urine flow. The outer prostate glands proper become compressed against the prostatic capsule during this growth, resulting in a thick pseudocapsule referred to as the surgical capsule.

The anatomic configuration of the prostate can have an important effect on the degree of obstruction produced. Some patients can develop primarily median lobe hyperplasia or just a hyperplastic posterior commissure of the bladder neck, which is commonly referred to as a median bar. In these settings, relatively small degrees of hyperplasia can result in major impairment of flow. The enlarging mass of hyperplastic tissue and the favorable or unfavorable anatomic configuration it takes are usually the major components of prostatic obstruction. The overall size of the prostate in BPH often correlates poorly with the degree of obstructive symptoms but can be predictive of the success or failure of various treatment modalities.

Dynamic Obstruction Prostate Smooth Muscle

The dynamic component of prostatic obstruction is related to the tone of the prostatic smooth muscle fibers. Smooth muscle fibers constitute a significant component of the true capsule, intervening stroma within the prostate, periurethral area, and the bladder neck.

Smooth muscle fibers of the prostate and bladder neck are richly innervated by adrenergic fibers of the sympathetic nervous system and ₁-type receptors. Specifically _1A-subtype receptors predominate within the prostate, whereas _1B-receptors mediate peripheral vasoconstriction. The baseline tone of the sympathetic autonomic nervous system is believed to modulate these smooth

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muscle fibers and, thus, prostatic urethral resistance. Medications containing adrenergic agonists (e.g., nasal decongestants) can result in worsening outlet obstruction or urinary retention. -Adrenergic blockers are effectively used to relax prostatic smooth muscle and thus lower bladder outlet resistance.

Detrusor Response

As outlet resistance increases, the bladder responds by increasing its force of contraction. By developing increased intravesical voiding pressures, the bladder can maintain flow and the appearance of normalcy. The added work to overcome outlet resistance results in detrusor hypertrophy, hyperplasia, and deposition of collagen within the bladder wall. This results in what is seen at cystoscopy as trabeculation, cellules, and diverticula. With thickening of the bladder wall, its normal elasticity is lost and compliance decreases. The loss of compliance results in a decrease in the functional capacity of the bladder, i.e., increased intravesical pressure for a given volume. These bladder changes also cause the development of detrusor instability, or loss of normal control over the reflex detrusor response.

Early in the course of obstruction, the bladder is able to compensate. However, with progression, irritative voiding symptoms (e.g., frequency, urgency, nocturia, and urgency incontinence) result. It is the irritative voiding symptoms that are most responsible for the patient's complaints. Untreated, this process can progress to severe bladder decompensation and dilatation, ureterovesical obstruction and hydroureteronephrosis, and, ultimately, renal insufficiency.

Diagnosis

Presentation/History

BPH is characterized by a spectrum of lower urinary tract symptoms (LUTS) previously referred to as prostatism:

Decreased force and caliber of stream
Hesitancy and straining to void
Interruption of stream
Postvoid dribbling
Sensation of incomplete emptying
Frequency and nocturia
Urinary retention (acute or chronic)

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LUTS (see Chapter 2) encompass both obstructive and irritative symptoms. Obstructive (voiding) symptoms (e.g., slow, weak stream) are a direct result of the increased outflow resistance, whereas irritative (storage) symptoms (e.g., frequency, urgency, nocturia) are secondary to bladder instability because of detrusor hypertrophy. Obstructive symptoms are the key feature. Irritative symptoms without obstructive symptoms are unlikely to be due to BPH. If irritative symptoms are the principal complaint, be alert for bladder cancer, infection, stones, or neurogenic bladder (such as Parkinson's disease or stroke) as the etiology. Exclude other causes of similar LUTS, such as polyuria from diabetes or congestive heart failure, history of urethral strictures, or medications (anticholinergics, antidepressants, or nasal decongestants).

A detailed and careful history and symptom assessment are critical. Symptom assessment can be enhanced by use of the International Prostate Symptom Score (IPSS) and the BPH Impact Index (BII). The IPSS is a data collection tool consisting of seven questions for the patient that quantitate his symptom severity. The maximum score is 35. A score of 0 to 8 is regarded as mild, 9 to 19 as moderate, and 20 or above as severe. BII quantifies how bothersome the symptoms are.

Differential Diagnosis

Bladder cancer
Infection (cystitis or prostatitis)
Bladder stones
Neurogenic (Parkinson's disease, stroke, dementia, multiple sclerosis, spinal cord injury, etc.)
Prostate cancer
Bladder neck contracture or urethral stricture
Medications (anticholinergics, antidepressants, decongestants, etc.)

Workup

Physical Examination

The digital rectal examination (DRE) is important. Carefully palpate the prostate, paying attention to size, shape, and consistency. Any suspicious areas (see Chapter 3) should be biopsied. The patient's symptoms are a better indication of the degree of obstruction than the size of the gland on DRE; however, a large prostate increases the risk for acute urinary retention. Examine

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the lower abdomen for evidence of a palpable bladder. Examine the penis for evidence of phimosis or meatal stenosis.

Laboratory Data

Urinalysis and culture, blood urea nitrogen (BUN), creatinine, and prostate-specific antigen (PSA) should be obtained. Urinalysis may suggest other possible causes for a man presenting with LUTS. Measurement of renal function (BUN and creatinine) may alert one to the severity of the obstruction. PSA determinations can help diagnose unsuspected prostate cancer (see Chapters 3 and 22) and give an estimate of prostate volume. Patients with a PSA of more than 1.6 ng/mL are at increased risk of urinary retention.

Uroflow/Postvoid Residual Urine

Measurement of the urine flow rate is the single best noninvasive method of estimating the degree of outlet obstruction. Peak flow rates of less than 15 mL/second (assuming a voided volume of >150 mL) are strong evidence of significant outflow obstruction. Measurement of postvoid residual urine (PVR), generally by noninvasive transabdominal ultrasound, can help identify patients who will respond to watchful waiting, medical, or surgical therapy. Patients with very reduced urinary flow rates (<10 mL/second) and postvoid residuals of more than 200 mL are at increased risk of urinary retention. More extensive urodynamic studies are generally not indicated in the routine workup of BPH.

Intravenous Urogram

Although not routinely indicated, an intravenous urogram (IVU) provides information about the upper tracts as well as the degree of residual urine. J-hooking of the lower ureters or elevation of the bladder base suggests marked intravesical prostatic enlargement. An IVU as routine screening for males with BPH has a low yield of incidental pathology (15%) and should be obtained only when otherwise indicated.

Cystourethroscopy

Cystourethroscopy is the only direct method of evaluating prostatic obstruction. The degree of lateral and median enlargement can

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be estimated. Inspect bladder for trabeculation, cellules, and diverticula. Examine bladder neck for contracture, bar formation, or a prominent median lobe. Estimate length of the posterior urethra and perform a water test for occlusion. Other pathologic causes such as bladder tumor or stones can be excluded. Cystoscopy can be performed in the office or just before prostatectomy, depending on the degree of uncertainty of the diagnosis.

Treatment

Treatment options for BPH continue to increase yearly. Transurethral resection of the prostate (TURP) is still the gold standard for severely symptomatic (IPSS >20) and obstructive BPH; however, many less invasive options have become popular. Most of these methods use different techniques, which range from lasers, radiofrequency, and microwaves, to heat the prostate to cause vaporization or coagulation necrosis. Medical management, primarily using -blocker therapy or 5- reductase medications, is the first line of treatment for patients with moderately symptomatic BPH (IPSS 9 19). Watchful waiting is appropriate for men with uncomplicated non-bothersome BPH.

Medical Therapy

-₁-Blockers

-₁-Adrenergic blocking agents are the most effective agents for relieving the IPSS symptoms of BPH. Tamsulosin (Flomax) is an antagonist of _1A-subtype adrenergic receptors in the prostate and has been effectively used to relax prostatic smooth muscle fibers and decrease bladder outlet resistance. Terazosin and doxazosin appear to be as effective at relieving symptomatic BPH but have higher incidences of side effects (e.g., tiredness, dizziness, headache, and postural hypotension). A new -₁-blocker, alfzosin (Uroxatral), has a favorable pharmacokinetic profile which appears to minimize the typical side effects of this class of agents. Generally, -blockers have been shown to increase peak urine flow rate and improve symptom scores (IPSS ~ 2 points) in about 60%.

5- -Reductase Inhibitor

5- -Reductase inhibitors, such as dutasteride (Avodart) and finasteride (Proscar), are used to block intracellular conversion of testosterone to DHT. This approach attempts to shrink hyperplastic glands and reduce further progression of BPH. 5- -Reductase

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inhibitors have been most effective in reducing the incidence of acute urinary retention in males with very large prostates (>50 mL) and improve IPSS approximately 1 to 2 points.

Combination Medical Therapy

Combining -blocker therapy with a 5- reductase inhibitor has been shown in a 5-year long-term therapy study (MTOPS) to be superior to either agent alone at preventing progression of LUTS and BPH; however, cost-effectiveness issues have been raised.

Surgical Therapy

Transurethral Resection of Prostate

Surgery is the gold standard for the treatment of BPH and produces the best improvements in symptoms and urine flow rates. TURP is the preferred method for all but the largest prostates that can be shelled out by open prostatectomy. In any simple prostatectomy, either TURP or open, the outer prostate gland is left in the surgical capsule. These patients are still at risk for developing prostate cancer. (Note there is a 10% incidence of unsuspected prostate cancer found in tissue removed for benign disease.) Approximately 70% of patients with secondary irritative symptoms (e.g., frequency, urgency, and nocturia) can be expected to have relief of these symptoms within 6 months of a TURP. The remaining 30% with persistent symptoms may require anticholinergic agents to control detrusor instability.

Indications for Surgery

Urinary retention
Hydronephrosis (with or without impaired renal function)
Recurrent urinary tract infections (secondary to residual urine)
Bladder stone (secondary to residual urine)
Severe obstructive symptoms (with or without bladder instability)

Miscellaneous

Intraurethral Stents

Placement of metal self-retaining intraurethral stents may be effective in relieving urinary retention in patients who are not candidates for surgical management; however, complications of migration, encrustation, and discomfort limit their use.

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Electrovaporization

Electrovaporization is a modification of the standard TURP using a metal roller with the diathermy set to a high current causing direct vaporization of the prostate with less hemorrhage. Long-term efficacy is unproved.

Laser Prostatectomy

Laser ablation of BPH using a neodynium:yttrium-aluminum-garnet (YAG) laser causes both vaporization and coagulation necrosis of the prostate by the high temperatures produced. However, these high temperatures can also cause postoperative pain and difficulty voiding for prolonged periods. Long-term outcome studies are still pending.

Hyperthermia

Other forms of hyperthermia have used radiofrequency energy such as in transurethral needle ablation (TUNA) and microwave energy in transurethral microwave thermotherapy (TUMT). These methods attempt to spare the urethra, thus minimizing side effects. However, a period requiring catheterization after these procedures is not uncommon, and further long-term outcome data will be necessary to fully evaluate their efficacy. Serious thermal injury complications have been reported.