EVALUATION AND MEDICAL MANAGEMENT

Benign Prostatic Hyperplasia

August 2006

Author: Mark Bibler, M.D.

Competencies: Medical Knowledge, Patient Care

Learning Objectives: After reading this information you should be able to

1. Outline an appropriate initial evaluation of a man presenting with symptoms suggesting BPH.

2. Identify which patients need treatment for BPH.

3. Discuss the available medical therapies for BPH.

Key Points

· BPH affects 50% of men at age 60 and as many as 90% by age 85

· Measurement of the serum PSA should be offered to the following patients: 1) those with at least a 10-year life expectancy and for whom knowledge of prostate cancer would change management; or 2) those for whom the PSA measurement may change the management of their voiding symptoms

· The AUA Symptom Index should be used as the symptom-scoring instrument in the initial assessment of each patient presenting with BPH

· The individual perception of the severity of symptoms and the extent to which they interfere with quality of life should be the primary considerations in choosing among therapeutic alternatives

· Treatment options for patients with bothersome moderate to severe symptoms include watchful waiting, medical therapy, or surgical therapy

INTRODUCTION

A common disease of aging men, benign prostatic hyperplasia (BPH) can be associated with bothersome lower urinary tract symptoms (LUTS) that have a significant impact on quality of life by interrupting normal daily activities and sleep patterns. In 2003 a committee was formed by the American Urological Association to update practice guidelines on the diagnosis and treatment of BPH. After an extensive review of prior guidelines and current medical literature, the committee promulgated the evidence-based guidelines that follow. They have been abridged for this discussion. The full text publication is available at www.auanet.org/guidelines/bph.cfm.

The prevalence of histopathologic BPH increases with age, affecting 50% of men at age 60 and as many as 90% by age 85. Although the prevalence of LUTS parallels that of BPH, only about half of those men with histologic BPH have moderate to severe LUTS. Moreover, the degree to which patients find these symptoms bothersome may differ widely among those with the same degree of symptom frequency and severity. The risk of measurable medical complications from BPH such as complete urinary retention and post-obstructive renal failure is quite low. Because the impact and natural history of BPH and associated LUTS on a given patient’s quality of life are highly variable, his individual perception of the severity of his symptoms and the extent to which they interfere with his quality of life should be the primary considerations in choosing among therapeutic alternatives.

Benign prostatic hypertrophy is defined histologically as a disease process characterized by stromal and epithelial cell hyperplasia beginning in the periurethral zone of the prostate. Patients with associated LUTS complain most often of urinary frequency, urgency, nocturia, decreased or intermittent force of stream, and incomplete bladder emptying. The relationship between BPH and LUTS is complex. As above, not all men with histologic BPH will develop LUTS. Conversely, not all men with LUTS and BPH have prostate enlargement.

DIAGNOSTIC EVALUATION

It is important to note that LUTS are not specific for BPH and may be caused by a variety of other urinary tract problems. Nonprostatic causes of these symptoms can be excluded in most cases on the basis of medical history, physical examination, and limited lab tests.

Recommended: In the initial evaluation of all patients presenting with LUTS suggestive of BPH:

· A medical history should be taken to identify other causes of voiding dysfunction or comorbidities that may complicate treatment.

The history should elicit underlying general medical conditions that can lead to bladder dysfunction or excessive urine production. Examples would include neurologic disorders, diabetes, and diuretic use. The urologic history should focus on irritative symptoms that might suggest infection or malignancy and prior episodes of urethritis, catheterization or surgery that could lead to stricture formation. Family history of BPH and prostate cancer is important. A patient voiding diary where the frequency and volume of each void are recorded is helpful in distinguishing between urinary frequency and polyuria especially in patients with nocturia.

· A physical exam, including both a digital rectal exam and a focused neurologic exam, should be performed.

Locally advanced prostate cancer can usually be excluded as a cause for LUTS by DRE. Although DRE tends to underestimate true prostate size, the finding of an enlarged prostate may affect the choice of pharmacologic treatment alternatives (see below). A focused neurologic exam should include a patient’s general mental status, ambulatory status, lower extremity neuromuscular status, and anal sphincter tone.

· A urinalysis should be performed by dipstick testing or microscopic examination of the urinary sediment to screen for hematuria and UTI.

Bladder cancer, UTI, urethral stricture, and distal urethral or bladder stones can all produce LUTS in aging men. A normal urine examination makes these conditions less likely although it does not rule them out.

· Measurement of the serum PSA should be offered to the following patients: 1) those with at least a 10-year life expectancy and for whom knowledge of prostate cancer would change management; or 2) those for whom the PSA measurement may change the management of their voiding symptoms (recommendation based on the Panel’s expert opinion).

Serum PSA has been shown to be a predictor of the natural history of BPH. Men with higher PSA values have a higher risk of future prostate growth, symptom and flow rate deterioration, acute urinary retention, and prostate surgery. This recommendation does not address the potential value of PSA screening for prostate cancer in asymptomatic men. In most patients a normal DRE should be sufficient to exclude locally advanced cancer as a cause of voiding dysfunction. If found, however, significant elevation of the PSA may be evaluated by further diagnostic testing to exclude malignancy.

Not recommended: The routine measurement of serum creatinine levels is not indicated in the initial evaluation of men with LUTS secondary to BPH (recommendation based on the Panel’s expert opinion).

Baseline renal insufficiency appears to be no more common in men presenting with BPH than in men in the general population. If the history or urinalysis suggest the possibility of underlying renal disease or urinary retention, then measurement of serum creatinine may be desirable particularly if imaging studies using intravenous contrast are anticipated.

SYMPTOM ASSESSMENT

Most patients who seek treatment for BPH do so because symptoms alter quality of life. On the other hand, patients who acknowledge moderate to severe voiding symptoms may not find these symptoms to be sufficiently bothersome to warrant treatment. Symptom quantification is therefore of importance in determining severity of disease and response to treatment.

Recommended: The AUA Symptom Index should be used as the symptom-scoring instrument in the initial assessment of each patient presenting with BPH.

Symptom score changes and the degree of each patient’s bother due to the symptoms should be the primary determinants of treatment response or disease progression. See the instrument below. A score of 7 or less indicates mild symptoms and 8 or greater indicates moderate to severe symptoms. Symptom scores alone do not delineate the morbidity of the problem as perceived by an individual patient. Therapeutic intervention may be indicated for a patient with moderate symptoms who finds his symptoms bothersome but not for a patient with severe symptoms who finds his symptoms tolerable.

Optional: Determination of the urinary flow rate and post-void residual may be helpful in those patients desiring invasive therapy.

A lower urinary flow rate may predict a favorable response to surgery but does not correlate with response to medical therapies. Within the range of 0-300 ml, the PVR does not predict the response to medical therapy. Many patients tolerate this degree of urinary retention without infection, progression to renal insufficiency, or bothersome symptoms.

TREATMENT

From the initial evaluation the physician should determine the degree of symptoms and the morbidity they cause to the individual patient. Treatment recommendations depend on both factors.

Recommended: Patients with mild symptoms of BPH (AUA Symptom Score of 7 or less) and patients with moderate or severe symptoms who are not bothered by their symptoms should be managed using a strategy of watchful waiting.

Patients who have only mild symptoms or who are not bothered by their symptoms generally will not benefit from therapy because these symptoms do not significantly impact their quality of life. The risks of medical therapy—including cost, the need to take daily medication, and side effects—may outweigh the benefits in this group. Symptoms may be reduced by reducing fluid intake at bedtime and decreasing caffeine and alcohol intake generally.

Recommended: Treatment options for patients with bothersome moderate to severe symptoms include watchful waiting, medical therapy, or surgical therapy.

Information regarding the risks and benefits of all therapeutic options should be discussed with the patient at this point. Patients choosing medical therapy may be prescribed the most appropriate agents at this time without additional testing. The published AUA guideline provides tables that attempt to quantify the benefit to be expected from multiple different medical and surgical therapies.

· Alpha-adrenergic blocker therapy. Alfuzosin, doxazosin, tamulosin, and terazosin are appropriate treatment options for patients with LUTS secondary to BPH. Alpha-blocker therapy is based on the hypothesis that clinical BPH is partly caused by alpha-1-adrenergic-mediated contraction of prostatic smooth muscle, resulting in bladder outlet obstruction. These medications block the receptor and thereby relieve the obstruction. They are efficacious in men with either normal or enlarged prostates. Side effects include orthostatic hypotension, dizziness, fatigue, nasal congestion, and ejaculatory dysfunction. All four drugs are equally efficacious when titrated to their maximal doses. There are slight individual differences in their side effect profiles.

· 5 Alpha-reductase inhibitor therapy. Finasteride and dutasteride are appropriate and effective treatment for symptomatic patients with prostatic enlargement. They can reduce the size of the prostate and retard progression of prostatic enlargement. They also reduce the risk of acute urinary retention and the need for future surgery. They are less effective than the alpha-blockers in reducing symptoms. They provide no benefit in men without enlarged prostates. Side effects are uncommon and include decreased libido, ejaculatory dysfunction, and erectile dysfunction.

· Combination therapy. In short-term studies, the combination of an alpha-blocker and a 5 alpha-reductase inhibitor has shown no greater symptom relief than an alpha-blocker alone. However, in a recent 5-year study, combination therapy did demonstrate a significant reduction in progression of symptoms and development of acute urinary retention and surgery compared to alpha-blocker therapy alone. Patients most likely to benefit from combination therapy are those with larger prostates and higher PSA values.

· Surgical therapy. A wide variety of minimally-invasive and more invasive surgical options are available for patients who prefer a surgical approach or who have failed attempted medical therapy. These options and their relative expected effectiveness are discussed in the guideline paper.

CASES AND QUESTIONS

1. A 60-year-old traveling salesman presents to the office complaining of frequent urination and nocturia. He often has to stop to find a restroom while traveling and complains of poor sleep. He notes mild diminution of his force of stream but no dysuria or hematuria. Past medical history is unremarkable. He currently takes no medications. He smokes 1 pack of cigarettes per day and does not drink alcohol. His father had surgery for prostate problems. His general physical examination is normal. His prostate does not feel enlarged and has no nodules.

Which initial tests should you order for this patient?

A. UA

B. PSA

C. Creatinine

D. Ultrasound of the bladder and kidneys

2. The tests you have ordered above all come back normal. What two additional tests should you consider before discussing therapeutic alternatives with this patient?

3. You have made a diagnosis of BPH in this patient. What medical therapy would you suggest to him?

A. Watchful waiting

B. An alpha-blocker

C. A 5 alpha-reductase inhibitor

D. Both B and C

4. A 60-year old man comes for his annual physical exam. He denies any ongoing complaints or medical problems, but on review of systems he admits to urinary frequency, decreased force of stream, intermittency, and nocturia three times per night. He is not concerned about these symptoms. Past medical history is unremarkable. He currently takes no medications. He smokes 1 pack of cigarettes per day and does not drink alcohol. His father had surgery for prostate problems. His general physical examination is normal. His prostate is enlarged and has no nodules.

After initial evaluation, you have made a diagnosis of BPH in this patient. What medical therapy would you suggest to him?

A. Watchful waiting

B. An alpha blocker

C. A 5 alpha-reductase inhibitor

D. Both B and C

5. One year later the patient returns stating that his symptoms have progressed and he now feels that he is not emptying his bladder completely. He wants to re-evaluate his treatment for BPH but does not want surgery. An ultrasound exam shows a post-void residual of 200cc. What therapy would you suggest?

A. Watchful waiting

B. An alpha-blocker

C. A 5 alpha-reductase inhibitor

D. Both B and C

E. Surgical referral despite the patient’s reluctance

ANSWERS

1. Answer A, urinalysis. Voiding symptoms are not specific for BPH and may also be due to infection, bladder cancer, stone disease, or urethral stricture. A normal urinalysis makes these alternatives less likely. A normal DRE excludes locally advanced prostate cancer as a cause for the patient’s voiding symptoms. A PSA may be offered if it will change the management of the patient’s symptoms—in this case discovery of occult prostate cancer, an issue unrelated to the present discussion. Although an elevated PSA may be correlated with progression of symptoms over time, it is unlikely to be elevated in the face of a normal prostate exam. Baseline creatinine determination is not recommended because renal insufficiency appears to be no more common in men presenting with BPH than in men in the general population. Determination of post-void residual is not recommended in patients not being considered for surgery. Elevation of PVR up to 300 ml does not predict response to medical therapy. Many patients tolerate this degree of retention without UTI or development or renal insufficiency.

2. Appropriate additional studies at this juncture would include a voiding diary and completion of the AUA Symptom Index for BPH. A log wherein the frequency and volume of each void are recorded helps to distinguish true polyuria as might be seen with diabetes, peripheral edema, or renal concentrating abnormalities from simple urinary frequency. The AUA Symptom Index permits quantification of the severity of the patient’s voiding symptoms and can be monitored over time to assess response to therapy or progression of disease. (Note: we will have the AUA symptom index available soon in the new handout bins in the practice).

3. Answer B, an alpha-blocker. The efficacy of alpha-blockers in reducing obstructive voiding symptoms has been well established in multiple clinical studies. Although this patient has a normal prostate exam, he has moderately severe symptoms that significantly impact his quality of life; watchful waiting is therefore not an appropriate alternative. Therapy with 5 alpha-reductase inhibitors is not efficacious in patients without prostatic enlargement.

4. Answer A, watchful waiting. Although this patient has moderately severe voiding symptoms, he does not find them sufficiently bothersome to warrant treatment. The risks of medical therapy including cost and side effects outweigh the benefits in this patient. Therapy with alpha-blockers may improve his symptoms but will not alter disease progression. Therapy with a 5 alpha-reductase inhibitor may slow the progression of his disease, but the admittedly small risks are not justified in a patient without intolerable symptoms.

5. Answer D, combination therapy with an alpha-blocker and a 5 alpha-reductase inhibitor. Watchful waiting is no longer an appropriate option since the patient is now symptomatic. Treatment with an alpha-blocker alone will provide symptomatic relief but will not alter the natural history of disease progression. Treatment with a 5 alpha-reductase inhibitor alone will also provide symptomatic relief but to a lesser extent than with an alpha-blocker. A long-term study has shown that combination therapy with an alpha-blocker and a 5 alpha-reductase inhibitor not only provided symptomatic relief but also reduced the size of the prostate and reduced the risk of acute urinary retention and the need for surgery. Combination therapy therefore appears to be the optimal choice for symptomatic men with prostatic enlargement. Although the patient had a significant PVR, this does not predict response to medical therapy and is not in and of itself an indication for surgery.