CHAPTER 29

BENIGN PROSTATIC HYPERPLASIA

Richard Morel, M.D.

  Table of Contents

            Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate.  It is the most common cause of bladder outlet obstruction in the male geriatric population and is highly prevalent in men over 40 of all races and cultures.  Occasionally it can lead to complications including urinary retention, renal insufficiency, urinary tract infections, gross hematuria and bladder stones, but the vast majority of patients present with symptomatic complaints including urinary frequency, nocturia, urgency, hesitancy, weak stream, intermittent stream or the sensation of incomplete bladder emptying.  This chapter will discuss the prevalence of prostatism, pathophysiology of BPH and outlet obstruction, initial evaluation of the patient, and both medical and surgical treatment options.

Prevalence and Incidence

            Benign prostatic hyperplasia is the most common nonmalignant neoplasm in older men.  Microscopic evidence of BPH is found in 50 percent of men by the age of 60 and 90 percent of men by the age of 85.[i] It is estimated that one in every four males will seek treatment for BPH by the age 80. Transurethral resection of the prostate (TURP) is the second most common surgical procedure in men over 65, second only to cataract surgery with approximately 300,000 to 400,000 resections performed each year.  In a population based survey of men over 60 with no history of prostate surgery the prevalence of one or more symptoms of prostatism (hesitancy, straining, weak stream, intermittency or use of a catheter) was 35 percent. The annual incidence rates during one and two years of follow up were 16.4 percent and 16.1 percent respectively.[ii]

Pathophysiology

            BPH is due to excessive cellular growth of both the glandular and stromal components of the prostate gland.  This growth is androgen sensitive and does not develop in men who have been castrated; castration has also been shown to promote regression.  This excessive growth originates in the transition zone of the prostate which surrounds the urethra leading to compression of the urethral lumen and symptoms of obstruction.

Patient Evaluation

            The presumptive diagnosis of BPH can be made when a male patient over the age of 50 presents with one or more symptoms of prostatism. The Agency for Health Care Policy and Research has published guidelines for evaluation and management of patients with BPH.[iii]  It is recommended that all patients presenting with symptoms of prostatism have as part of their initial evaluation: complete medical history with special attention focused on the urinary tract, a complete physical exam including a digital rectal exam, urinalysis and serum creatinine. Measurement of prostate-specific antigen (PSA) is considered optional.  Tests which may be helpful include uroflowmetry – this may be helpful in identifying patients with low urine flow rates who may benefit more from therapy and as a means of following therapy.  Post-void residual (PVR), preferably measured by ultrasound, can be used to identify patients with higher PVR who may also be more likely to benefit from therapy.  Pressure-flow studies may be useful in distinguishing patients who may have some component of bladder dysfunction.   Tests that are presently not recommended as part of the initial evaluation include imaging of the upper urinary tract by ultrasound or intravenous urography, filling cystometry and urethroscopy.

            Formal assessment of symptom severity is best done by using the American Urological Association (AUA) Symptom Index for BPH. The index is a self- or physician-administered questionnaire (Figure 1) which has been found to correlate highly with a subject’s global ratings of the magnitude of their urinary problem.  It has also been found to be clinically responsive.[iv]  Symptoms are classified as mild (0 - 7), moderate (8 - 19) and severe (20 - 35).  The index should be used in treatment planning and in periodic reassessment.

Treatment

            A treatment plan should be guided by the severity of symptoms and patient preferences.  For patients who have mild symptoms by the AUA index, watchful waiting is the appropriate treatment. 4  It is not currently possible to predict which of these patients will have progression of symptoms or complications of the disease.  In a survey of patients with mild symptoms, 37.5 percent reported no symptoms one year later, and only 12.5 percent progressed to severe symptoms.2  These patients should be reassessed on a regular basis with symptom index, physical exam and routine laboratory tests (UA, creatinine).  Patients with moderate to severe symptoms should be educated about the different treatment options and an informed decision be made according to the patient’s preferences.  These treatment options include watchful waiting, medical therapy and surgery.  Any patient with a complication of BPH (refractory retention, recurrent UTIs, recurrent or persistent hematuria, bladder stones, renal insufficiency) should be referred for surgery. 4

Medical Therapy

             Alpha-1-adrenergic receptor blockers (terazosin, doxazosin, prazosin) block the adrenergic receptors in hyperplastic prostatic tissue, the prostatic capsule and the bladder neck.  This results in decreased smooth muscle tone and a decrease in resistance to urinary flow through the bladder neck and prostatic urethra.[v]  The alpha-adrenergic antagonist that has been most studied is terazosin.  In a randomized, double-blind, placebo-controlled, multicenter study of 285 men with symptomatic BPH randomly assigned to receive placebo, or 2, 5, or 10mg of terazosin administered once daily for 12 weeks, the men in the 5 and 10 mg terazosin groups had a significantly greater decrease in symptom score compared to those who received placebo. The percentage reduction in symptom index for placebo, and 2, 5 and 10mg treatment groups were 23 percent, 32 percent, 32 percent and 44 percent respectively.  The group receiving 10mg of terazosin also had a statistically significant increase in urinary peak flow over the placebo group.[vi]  In a second study of 160 men over 45 years of age and with symptoms of BPH, the terazosin treated group  had a 42 percent decrease in symptoms score and a 30 percent increase in urinary peak flow compared to 11 percent and 14 percent respectively for the placebo group.[vii]  The time to maximal benefit was 4 to 6 weeks.  The side effects of terazosin in each of these studies included dizziness (10 - 19 percent) and postural hypotension (8.3 percent) with one patient in the 10 mg treatment group suffering a syncopal episode. These results suggest that terazosin given once daily in doses up to 10 mg is effective in alleviating the symptoms of BPH.  We recommend starting with a low dose (1mg daily) and titrating up over two to three weeks to a maximum of 10 mg/day.

            5 alpha-reductase inhibitors: Within the prostate, 5 alpha-reductase enzymatically converts testosterone to dihydrotestosterone.  Blockage of this enzyme results in androgen deprivation within the prostate.[viii] Finasteride is a potent inhibitor of 5 alpha-reductase.  In a randomized, double-blind, multicenter, placebo controlled study, 895 men with symptoms of BPH and an enlarged prostate by digital rectal exam were treated with finasteride (1 mg/day or 5 mg/day) or placebo.  As compared with the men in the placebo group, the men treated with finasteride 5mg/day had a significant decrease in the total urinary-symptom scores (21 percent vs. 2 percent), an increase of 1.6 ml/sec in maximal urinary-flow rate and a 19 percent decrease in prostatic volume.[ix] The changes in symptoms score reached statistical significance after 2 months of therapy.  These results have been replicated in several other studies. [x]’[xi]’[xii] The side effects in these trials included decreased libido, ejaculatory dysfunction and impotence in approximately 5 percent of the patients.

     Comparison of medical therapies: A recent trial compared placebo, terazosin (10mg/day), finasteride (5mg/day) and the combination of both drugs in 1229 men 45 to 80 years of age with symptomatic BPH.  AUA symptom index scores and urinary flow rates were evaluated at baseline and follow up for one year.  The mean changes from base line symptom scores in the placebo, finasteride , terazosin and combination therapy group were 2.6, 3.2, 6.1 and 6.2 points respectively.  Urinary flow rates increased 1.4, 1.6, 2.7 and 3.2 ml/sec respectively.[xiii] The conclusion of the authors of this study was that in men with BPH, terazosin was effective whereas finasteride was not and the combination of the two was no more effective than terazosin alone. One important note to make on the difference between this study and the previous studies on finasteride is that in this study an enlarged prostate was not a criterion for entrance into the study and the average prostatic volume was 37 ml whereas in all of the previous studies on finasteride, prostatic enlargement was a criterion for admission and the average prostate size ranged from 47 to 60 ml.  In conclusion it appears that terazosin is more effective and has a more rapid onset of action than finasteride and should therefore be used as a first line agent, but in men with an enlarged prostate finasteride may be a reasonable option.

Surgical Therapy

            Transurethral resection of the prostate (TURP) is the most common surgical treatment for BPH, and prior to the recent developments in medical and newer surgical therapies it was the mainstay of treatment.  A multicenter, randomized trial was conducted comparing TURP with watchful waiting in 556 men with moderate symptoms of BPH with a primary endpoint of treatment failure, defined as death, repeated or intractable urinary retention, a residual urinary volume of >350 ml, the development of bladder calculus, new and persistent incontinence, a high symptom score, or a doubling of the serum creatinine.  After an average follow-up of 2.8 years, TURP was superior to watchful waiting in preventing treatment failure (23 vs. 47 patients respectively) and in improving symptom scores (mean score at follow-up, 4.9 vs. 9.1, change from baseline,    -9.6 vs. -5.5).[xiv]  Surgery in this study was not associated with impotence or urinary incontinence, however in other studies erectile dysfunction that was not present preoperatively occurred in 10 to 15 percent of patients and retrograde ejaculation occurred in at least one third of patients. 9

In a retrospective review of 3,885 patients who underwent TURP, the postoperative mortality rate was 0.2 percent and the immediate postoperative morbidity rate included failure to void (6.5 percent), bleeding requiring transfusion (3.9 percent), genitourinary infections (2.3 percent) and discharge from hospital with indwelling catheter (2.4 percent).[xv]  In conclusion, surgery appears to offer the best chance for symptom improvement but it also has the highest complication rates.  Other minimally invasive surgical treatments have developed in recent years. The best studied of these is transurethral incision of the prostate (TUIP).  It appears to have the same efficacy as TURP with fewer side effects, but it is limited to men with prostates of 30 grams or less. 4  Prostatic stents, microwave therapy and laser prostatectomy are all being studied at present, but not enough data are published to draw conclusions at this time.  Balloon dilatation of the prostatic urethra is less effective than surgery but can provide temporary relief of symptoms (<2 years) with few complications.  Of note surgery need not be left as a treatment of last resort.  Some patients may prefer to undergo a surgical procedure over being placed on chronic medical therapy.  Surgery is also the treatment of choice for any patients with complications of BPH.