Benign prostatic hyperplasia

Contributors of Campbell-Walsh-Wein, 12th edition

Paolo Capogrosso, Andrea Salonia, Francesco Montorsi, Sevann Helo, R. Charles Welliver Jr., Kevin T. Mcvary, Misop Han, Claus G. Roehrborn, and Douglas William Strand

Epidemiology and pathobiology

Benign prostatic hyperplasia (BPH), a noncancerous enlargement of the prostate gland, is the most common benign tumor found in men. BPH is a pathologic process but certainly not the only cause of lower urinary tract symptoms (LUTS) in aging men. Despite intense research efforts to elucidate the underlying etiology of BPH, cause-and-effect relationships have not been established. Previously held notions that the clinical symptoms of male LUTS are caused by a mass-related increase in urethral resistance are too simplistic. It is now clear that symptoms are caused by age-related detrusor dysfunction and other conditions such as polyuria, sleep disorders, and a variety of systemic medical conditions unrelated to the prostate-bladder unit.

It is well recognized that voiding symptoms poorly correlate with underlying pathophysiology. This has led to the recognition that LUTS may commonly be related to bladder outlet obstruction (BOO) as a result of benign prostatic obstruction (BPO), which is often associated with benign prostatic enlargement resulting from the histologic condition of BPH ( Fig. 21.1 ). Failure to empty can be related either to an outlet obstruction, detrusor under activity of the bladder, or a combination of both. Postmicturition symptoms, such as post void dribbling, are very troublesome and may cause significant interference with quality of life.

LUTS symptoms are encompassed by the term overactive bladder (OAB) syndrome, which is defined as urgency, frequency, nocturia, and urgency incontinence (irritative symptoms) , and are believed to be correlated with an underlying detrusor over activity. These symptoms tend to be more bothersome, especially if they are associated with incontinence. Storage (obstructive) symptoms include hesitancy, intermittent stream, straining to void, prolonged micturition, feeling of incomplete emptying, and dribbling . LUTS (both irritative and obstructive) can also be associated with urinary infections or, more rarely, with other conditions, such as bladder stones, carcinoma, or carcinoma in situ in the bladder and must be differentiated.

Histopathologically, BPH is characterized by an increased number of epithelial and stromal cells in the periurethral area of the prostate. The precise molecular etiology of this hyperplastic process is uncertain. Androgens, estrogens, stromal-epithelial interactions, growth factors, and neurotransmitters may play a role, either singly or in combination, in the etiology of the hyperplastic process.

The pathophysiology of BPH is complex. Prostatic hyperplasia increases urethral resistance, resulting in compensatory changes in bladder function. However, the elevated detrusor pressure required to maintain urinary flow in the presence of increased outflow resistance occurs at the expense of normal bladder storage function. Obstruction-induced changes in detrusor function, compounded by age-related changes in both bladder and nervous system function, lead to urinary frequency, urgency, and nocturia, the most bothersome BPH-related complaints.

There is no globally accepted epidemiologic definition of BPH since the pathological manifestation and the clinical symptom complex poorly coincide in many men. The prevalence of BPH thus can either be calculated based on histologic criteria (autopsy prevalence) or clinical criteria (clinical prevalence). Numerous other demographic and environmental factors have been suggested as risk factors or contributors to the disease process, including religion, socioeconomics, sexual activity, vasectomy, alcohol use, liver disease, hypertension, smoking, and obesity.

As is true for prostate cancer, BPH occurs more often in the West compared with Eastern countries, such as Japan and China, and may be more common among blacks. Not long ago, a study found a possible genetic link for BPH in men younger than age 65 years who have a very enlarged prostate: Their male relatives were four times more likely than other men to need BPH surgery at some point in their lives, and their brothers had a six fold increase in risk.

Clinical manifestations

The presentation of LUTS is often that of BOO secondary to BPH. Symptoms may significantly and impair health-related quality of life and are classified as voiding (hesitancy, weak stream, straining, and prolonged voiding), storage (frequency, urgency, nocturia, urge incontinence, and voiding of small volumes), or postmicturition (post void dribble, incomplete emptying). Most men who have LUTS present with a combination of these symptoms. Although rare in the present day, some men present with urinary retention as the initial sign of BPH/LUTS, and this often heralds the need for surgical intervention.

The American Urological Association (AUA)/IPSS (International Prostate Symptom Score) (0–35) and associated bothersome index score (0–6) ( Fig. 21.2 ) are routinely utilized and documented into the medical record to gauge the degree of risk (low [0–7], moderate [8–19], or high [20–35]) and degree of bother related to the symptoms. This risk level can guide management (conservative, medical or surgical) and be used to gauge success of therapy or progression of disease.

Key Points

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The autopsy prevalence of benign prostatic hyperplasia (BPH) increases linearly starting at 40 years of age and is remarkably similar across cultures and ethnicities.
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Cross-sectional studies suggest increases KEY in lower urinary tract symptoms (LUTS) severity, frequency, bother, and quality-of-life impairment with age that are fundamentally similar in all societies studied.
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Analytical studies have failed to reveal significant risk factors for the development of BPH and LUTS.
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The natural history of BPH in individual patients is highly variable and measured primarily by prostate volume growth
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Inter individual variability is also noted in secondary physiologic measures such as urinary flow and residual urine, the development of complications, the risk for urinary retention and the need for surgery.
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There are certain baseline factors allowing an assessment of risk for volume growth, progression, and risk for complications.

Diagnosis and testing

Physical examination and a complete history are an important first step in the basic workup of every patient complaining of LUTS and should not be neglected. Assessment should begin with a medical history and review of medications. The history should include questions related to any causes that may lead to bladder dysfunction, such as cerebrovascular disease, previous surgical procedures, and history of prostatic disease (inflammatory, benign, and cancer). Document onset and duration of symptoms, sexual history, and previously attempted treatment(s).

Medications, such as diuretics, and over-the-counter preparations, such as nasal decongestants and antihistamines, exacerbate urinary symptoms. Additionally, dietary factors such as water intake, caffeine, and alcohol use can contribute to the clinical manifestations of LUTS symptoms.

The exam should accurately assess the male pelvis, mostly to identify disorders potentially associated with LUTS. To this aim, examine the suprapubic area and palpate for a bladder; inspect the penis for evidence of a urethral stricture or phimosis and the scrotum and testicles. An elevated body mass index and signs suggestive for metabolic syndrome should be noted. In addition, the motor/sensory functions of the perineum and the lower limbs should be assessed to rule out neurologic alterations. As the last step of the physical assessment, a digital rectal examination should be performed to estimate volume and texture of the prostate.

Additionally, voiding charts and diaries can provide useful information. Urinalysis (dipstick and microscopic exam) is performed looking for blood, pyuria, and crystals. Urine cytology may be ordered if history of smoking indicates. Serum prostate-specific antigen (PSA) can be ordered to estimate prostate volume (PSA <1.6, >2, and >2.3 predicts prostate volume >40 cc for men in their 50s, 60s, and 70s, respectively) and need for further prostate cancer evaluation (if history of 5-α-reductase use PSA will be lower). Uroflowmetry (normal >15 cc/sec), postvoid residual measurement, (normal <30 cc – severe >300 cc), and pressure-flow studies may be ordered in select patients. Urodynamic studies are considered optional and best suited for patients who demonstrate LUTS in which the diagnosis of BOO is unclear.

Before surgical intervention, clinicians should consider assessment of prostate size and shape via abdominal or transrectal ultrasonography (TRUS) or cross-sectional imaging (i.e., magnetic resonance imaging [MRI] or computed tomography [CT]). Cystourethroscopy should be reserved for those with gross hematuria, history or suspicion of bladder cancer, recurrent severe urinary tract infection (UTI), crystals suggestive of bladder stone, or trauma.

Key Points

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Assessing symptom severity is the first step in the workup of patients with lower urinary tract symptoms.
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The prostate-specific antigen test should be considered for patients with a life expectancy longer than 10 years.
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Ultrasound imaging and uro-flow measurement should be considered for patients with moderate to severe symptoms.
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Invasive urodynamic tests should be considered if bladder motility alterations are suspected.

Treatment

LUTS should be carefully assessed according to diagnostic algorithms ( Figs. 21.3 and 21.4 ) aimed to evaluate symptom severity and better understand the underlying pathologic condition. The clinical management is based on patients’ symptoms and expectations; besides conservative strategies, medical therapy and surgical interventions all play a major role throughout treatment management for men with BPH/LUTS. Physicians should maintain a careful balance between the potential benefits (symptom relief) and harm (adverse events) associated with each treatment modality and discuss with the patients appropriately.

Watchful waiting or conservative management

Conservative management is the preferred approach for patients with mild symptoms (IPSS 0–7) and without complicating factors. Watchful waiting is based on patient education, lifestyle interventions, and disease monitoring. Lifestyle modifications include proper daily fluid intake; tea, caffeine, and alcohol avoidance or restriction; and concurrent medication adjustment. Patients should be followed up yearly to detect worsening of symptoms or the occurrence of complications.

Medical treatment for LUTS

Medical therapy plays a major role in the management of patients with LUTS. The current drug armamentarium ( Table 21.1 ) includes α-adrenergic blockers (α1-blockers), 5-α reductase inhibitors (5-ARIs), antimuscarinic drugs, phosphodiesterase type 5 inhibitors (PDE5Is), β3-agonists, and numerous plant extracts (not listed). Of note, different combinations of medical compounds (α-blocker + 5-α-reductase inhibitor) also play a relevant role in the management of LUTS ( Fig. 21.5 ).

Key Points

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Conservative management is the preferred approach for patients with mild symptoms and without complicating factors.
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Watchful waiting is based on patient education, lifestyle interventions, and disease monitoring.
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Lifestyle modifications include proper daily fluid intake; tea, caffeine, and alcohol avoidance or restriction; and concurrent medication adjustment.
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Patients should be followed up early to detect worsening of symptoms or the occurrence of complications.

Table 21.1

Minimally Invasive and Surgical Options for Treatment of Lower Urinary Tract Symptoms

ANTIMUSCARINIC DRUGS	AVAILABLE FORMULATION	RECOMMENDED DAILY DOSE
Darifenacin ER	7.5-, 15-mg capsule	1 × day
Fesoterodine ER	4-, 8-mg capsule	1 × day
Oxybutynin ER	5-, 10-, 15-mg ^bcapsule	1 × day (up to 20 mg/day)
Oxybutynin IR	2.5-, 5-mg ^acapsule	3–4 × day (max, 20 mg/day)
Propiverine ER (no US)	30-mg capsule	1 × day
Propiverine (no US)	15-mg capsule	2–3 × day
Solifenacin	5-, 10-mg capsule	1 × day
Tolterodine IR	1-, 2-mg capsule	2 × day
Tolterodine ER	2-mg ^b, 4-mg capsule	1 × day 1 × day
Trospium IR	20-mg capsule	2 × day
Trospium ER	60-mg capsule	1 × day
β3 Agonist
Mirabegron	25-mg capsule	1 x day

CLASS OF α-BLOCKERS	AVAILABLE FORMULATION	RECOMMENDED DAILY DOSE	RECOMMENDED ADMINISTRATION
Nonselective
Terazosin	1 ^d, 2, 5, 10 ^dmg capsule	5 or 10 mg qi	Initial dose is 1 mg at bedtime. The dose should be titrated up to 5 or 10 mg.
Doxazosin IR	1-, 2-, 4-mg capsule	2–8 mg qd	Initial dose is 2 mg at bedtime. The dose should be titrated up to 4 or 8 mg.
Doxazosin SR	4-, 8-mg capsule	4 or 8 mg qd	Initial dose is 4 mg after breakfast, eventually increased to 8 mg.
Uroselective
Alfuzosin ER ^b	10-mg capsule	10 mg qd	Initial dose is 10 mg with the same meal each day.
Tamsulosin	0.4, 0.8 ^dmg capsule	0.4–0.8 mg qd	Initial dose is 0.4 mg with the same meal each day.
Silodosin	4-, 8-mg capsule	8 mg qd	Initial dose is 8 mg with the same meal each day.

FIVE α-REDUCTASE INHIBITORS	RECOMMENDED DAILY DOSAGE	COMMENTS
Finasteride	5 mg qd. Treatment is recommended for at least 6 months	• PSA levels decrease by approximately 50% • Finasteride is not indicated for PCa prevention -increased risk for high-risk disease • Patients should be warned regarding risk for sexual dysfunction and depression
Dutasteride	0.5 mg qd. Treatment is recommended for at least 6 months	• PSA levels decrease by approximately 50% • Dutasteride is not indicated for PCa prevention because of an observed increased risk for high-risk disease • Patients should be warned regarding risk for sexual dysfunction and depression