Pathophysiology, treatment

The condition
Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate gland that is due to both epithelial and stromal hyperplasia. Although the exact origin of this condition is not well defined, it is thought to arise as microscopic nodules in the periurethral tissue (transition zone) of the prostate gland in men as young as their late 20s. With advancing age and the presence of androgens, this histologically identifiable hyperplastic tissue progresses to a macroscopic state, which is a palpably enlarged prostate. This enlarged prostate can cause clinically significant obstruction of the bladder outlet in many men due to constriction of the urethra as it courses from the bladder neck to the external urinary sphincter. The constellation of symptoms associated with this intravesical obstruction is known as prostatism.

It is estimated that more than 16 million men in the United States suffer from prostatism or clinically significant BPH. Fifty percent of men over the age of 50 years have some degree of hyperplastic enlargement of the prostate, while 95% of men will experience symptoms related to this enlargement of the prostate by the time they reach the age of 85 years. Twenty-five percent of all patients seen by urologists suffer from BPH. Over 400,000 patients were treated surgically during 1990 in the United States, and worldwide during the same year, 1,200,000 men underwent a prostatectomy for symptomatic BPH. Although this represents only 4% of the number of patients with this condition, intervention can be expected to increase with the advent of efficacious, less invasive therapies. One source estimates that 2,250,000 interventions (medical, minimally invasive, and surgical) for BPH will be performed in the United States by the year 2000. Thus, it is safe to say that BPH is the single most prevalent condition treated in urologic practice today.

Making the diagnosis
When evaluating a patient with symptoms of prostatism, it is important to: 1) make sure that the symptoms are truly due to an enlarged prostate gland, and 2) assess the severity of the condition to determine whether therapeutic intervention is necessary. All patients with prostatism should be evaluated with both a digital rectal examination and serum prostate-specific antigen (PSA) determination to exclude a clinically significant prostate cancer. A urinalysis also should be performed to eliminate the possibility of an infectious process. In addition, it is wise to obtain a serum creatinine level to determine the baseline renal function; marked, longstanding bladder outlet obstruction due to BPH can result in kidney damage. Intravenous pyelography (IVP) should only be performed for select patients, such as men with a history of nephrolithiasis or an upper tract transitional cell carcinoma.

To assess the degree of bladder outlet obstruction, the single most useful test is the American Urological Association symptom index. This is a self-administered questionnaire consisting of seven questions relating to the ability to urinate (Fig. 1). A score between 0 and 7 is consistent with mild prostatism, 8 to 18 is indicative of moderate prostatism, 19 to 35 is compatible with severe prostatism. Only patients with moderate or severe bladder outlet obstruction should be considered candidates for therapy of any type.

Another diagnostic test that can provide objective information about a patient's ability to urinate is the urinary flow rate. It is an electronic recording of the velocity of the urine being expelled from the bladder during micturition and represents the single best noninvasive urodynamic test to assess bladder outlet obstruction. From several investigations, it has been learned that the peak value more specifically identifies men with BPH than does the mean rate. Also of importance is the fact that flow rate is dependent upon the patient's age and the volume of urine voided; with advancing age and decreasing urine volume, the flow rate diminishes. Nevertheless, for a man in the seventh and eighth decade of life who voids 150 ml or more, a peak urinary flow rate of 15 ml/second or greater should be interpreted as appropriate. On the other hand, a peak flow rate less than 10 ml/second in the same clinical setting is consistent with significant bladder outlet obstruction. Only in select patients is it necessary to obtain a "pressure-flow'' study, in which the intravesical pressure is monitored while the peak urinary flow rate is recorded. Cystoscopy should not be a part of the diagnostic evaluation unless a specific indication exists, such as hematuria.
Treatment options

In 1994, there are numerous medical, minimally invasive, and surgical treatments available for the management of symptomatic BPH (Table 2). It is beyond the scope of this chapter to discuss the scientific rationale, clinical results, advantages, and disadvantages of each. In the discussion that follows, a general overview is provided.

For the past 50 years, transurethral resection of the prostate (TURP) has been the mainstay of treatment for this condition. In recent times, it has been the second most common operation performed in men over 65 years of age in the United States; only cataract extraction was performed more frequently. Although TURP is an effective treatment for most patients with symptomatic BPH, it appears that approximately 20 to 25% of patients undergoing a TURP do not obtain a satisfactory, long-term outcome. Complications do occur and include retrograde ejaculation in most men (70-75%), impotence in 5 to 10%, some degree of urinary incontinence in 2 to 4%, and postoperative urinary tract infection in 5 to 10% of patients. Based on recent investigations published in the urologic literature, the risk of blood transfusion for patients undergoing a TURP is approximately 5 to 10%, and, thus, is a significant concern to many men in this era when various types of hepatitis and AIDS are increasing in prevalence. Another concern with TURP is that the reoperation rate is approximately 15 to 20% when patients are followed for 10 years or longer (2.2% per year). Also, several large-scale investigations have shown that the life expectancy of patients undergoing a TURP is less than that for men who receive an open prostatectomy as treatment for symptomatic BPH.

Because of these issues as well as the desire by men in our society to avoid surgery whenever possible, there has been tremendous interest in developing alternative treatments to TURP for the management of symptomatic BPH ( Table 2). These options include medical therapies, such as drugs that produce a state of androgen deprivation (luteinizing hormone-releasing hormone analogues, antiandrogens, and 5alpha-reductase inhibitors), alpha-adrenergic antagonists which eliminate the dynamic component of BPH, and aromatase inhibitors which eliminate the biosynthesis of estrogens in the male. In 1993, finasteride (Proscar), a potent 5 alpha-reductase inhibitor, became the first medication approved by the Food and Drug Administration (FDA) for the treatment of BPH. Terazosin (Hytrin), also with FDA approval for the indication of BPH, and doxazisin (Cardura) are selective alpha-1 adrenergic antagonists that are being used for the management of BPH. Adrenergic receptors in the prostatic adenoma and capsule mediate the tension in the smooth muscle of the prostate and blocking these receptors can decrease the resistance along the prostatic urethra.

Transurethral incision of the prostate (TUIP), a minimally invasive procedure, is being used with increasing frequency. When compared to TURP, TUIP is technically easier, can be performed more quickly, and has fewer side effects; patients can be discharged home the same or the following day, and the convalescence period is shorter than that for TURP. While enthusiasm for balloon dilatation of the prostate is diminishing as results of recent studies indicate that it is not an effective, long-term treatment, there is increasing interest in laser prostatectomy, and microwave therapy. Although both of the latter procedures are still investigational and not FDA-approved for widespread clinical use, preliminary data suggest that they can improve voiding symptoms. Prostatic stents, in FDA-approved clinical trials, have been demonstrated to improve the peak urinary flow rate and decrease the obstructive symptom score to a level similar to that of TUIP and TURP. Most recently, two other therapeutic modalities, transurethral needle ablation of the prostate (TUNA) and transrectal high-intensity focused ultrasound therapy (HIFU) have been developed and are currently being investigated in clinical trials in both the United States and Europe.

Summary
At the present time, the management of BPH is in a state of transition. TURP is no longer the only therapeutic option available. While it is still the most efficacious with regard to relieving bladder outlet obstruction and remains the gold standard of care, there are other treatment modalities that are attractive. The single most important advantage of medical therapies is that the patient can avoid a procedure; however, all medical treatments must be regarded as a life-time commitment, and their efficacy is not as good as the minimally invasive treatments. The surgical procedures, on the other hand, are a one-time event, but they are associated with greater risk and a recovery period.

In the future, it will be necessary to develop methods for deciding, on a scientific basis, the most appropriate treatment for each individual patient. However, once the physician has informed the patient of the benefits and risks of each therapy, the patient's preference must be considered because what is a risk to one may not be to another. With the physician and patient working together, the treatment can be tailored to the patient's specific needs and expectations.

Up to this point in time, the primary focus of investigation has been to develop the ``perfect'' treatment for BPH. In the years ahead, it will be important to gain a better understanding of both the pathogenesis of this disease process as well as the functional interaction that exists between the prostate gland and the bladder. In this manner, it may be possible to develop methods to prevent the disease or to identify it at an early stage so that clinically manifest BPH (prostatism) does not occur. Society would benefit tremendously.

Suggested Reading

Oesterling JE. Benign prostatic hyperplasia: its natural history, epidemiologic characteristics, and surgical treatment. Arch Fam Med 1992;1:257-266.

Barry MJ, Fowler FJ, Jr, O'Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, Cockett ATK and The Measurement Committee of the American Urological Association. The American Urological Association symptom index for benign prostatic hyperplasia. J Urol 1992;148:1549-1557.

Lepor H. Medical therapy for benign prostatic hyperplasia. Urology 1993;42:483-501.

McConnell JD, Barry MJ, Bruskewitz RC, et al. Benign Prostatic Hyperplasia: Diagnosis and Treatment. Quick reference guide for clinicians. No. 8. Rockville, M.D.: Department of Health and Human Services, 1994. (AHCPR publication no. 94-0583).

Oesterling JE. Benign prostatic hyperplasia: medical and minimally invasive treatment options. New England Journal of Medicine 1995;332:99-109.