NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

McConnell JD, Barry MJ, Bruskewitz RC. Benign Prostatic Hyperplasia: Diagnosis and Treatment. Rockville (MD): Agency for Health Care Policy and Research (AHCPR); 1994 Feb. (AHCPR Clinical Practice Guidelines, No. 8.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Cover of Benign Prostatic Hyperplasia: Diagnosis and Treatment

Benign Prostatic Hyperplasia: Diagnosis and Treatment.

Show details

3Initial Evaluation

Medical History

A detailed medical history focusing on the urinary tract, previous surgical procedures, general health issues, and fitness for possible surgical procedures is recommended.

Specific areas to discuss when taking the history of a man with BPH symptoms include a history of hematuria, urinary tract infection, diabetes, nervous system disease (for example, Parkinson's disease or stroke), urethral stricture disease, urinary retention, and aggravation of symptoms by cold or sinus medication. Current prescription and over-the-counter medications should be examined to determine if the patient is taking drugs that impair bladder contractility (anticholinergics) or that increase outflow resistance (sympathomimetics).

Physical Examination

A DRE and a focused neurologic examination are recommended.

The DRE and neurologic examination are done to detect prostate or rectal malignancy, to evaluate anal sphincter tone, and to rule out any neurologic problems that may cause the presenting symptoms. The presence of induration is as important a finding as the presence of a nodule.

The outcomes of these tests are not entirely known, and the specificity of the rectal examination for the detection of prostate cancer is limited. Only 26 to 34 percent of men with suspicious findings on DRE have positive biopsies for cancer (Thompson, Ernst, Gangai, et al., 1984 ; Chodak, Keller, and Schoenberg, 1988 ; Lee, Littrup, Torp-Pedersen, et al., 1988). The sensitivity is equally low and in one study was found to be only 33 percent (Vihko, Kontturi, and Lukkarinen, 1985).

Nevertheless, given the minimal expense, discomfort, and time involved, most patients would opt to have the DRE done. Although the Preventive Services Task Force (1989) could not recommend for or against inclusion of the DRE in periodic health examinations, that recommendation applies to screening of asymptomatic men and not specifically to aging men with symptoms of prostatism.

Furthermore, the rectal examination establishes the approximate size of the prostate gland. In patients who choose or require invasive therapy such as surgery or balloon dilation, estimation of prostate size is important to select the most appropriate technical approach. DRE provides a sufficiently accurate measurement in most of these cases.

However, the size of the prostate should not be considered in deciding whether active treatment is required. Prostate size does not correlate with symptom severity, degree of urodynamic obstruction, or treatment outcomes (Roehrborn, Chinn, Fulgham, et al., 1986 ; Simonsen, Moller-Madsen, Dorflinger, et al, 1987 ; Dorflinger, Bruskewitz, Jensen, et al., 1986 ; Bissada, Finkbeiner, and Redman, 1976 ; Meyhoff, Ingemann, Nordling, et al., 1981). If a more precise measurement of prostate size than can be obtained from a DRE is needed to determine whether to perform open prostatectomy rather than TURP, ultrasound (transabdominal or transrectal) is more accurate than intravenous urography or urethrocystoscopy.

Urinalysis

A urinalysis is recommended, either by using a dipstick test or by examining the spun sediment to rule out urinary tract infection and hematuria.

There is insufficient evidence that urinalysis is an effective screening procedure for asymptomatic men (Preventive Services Task Force, 1989). Because serious urinary tract disorders are relatively uncommon, the positive predictive value of screening for them is low, and the effectiveness of early detection and intervention is unproven.

However, in older men with BPH and a higher prevalence of these disorders, the benefits of an innocuous test such as urinalysis clearly outweigh the harms involved. The test permits the selective use of renal imaging and endoscopy for patients with the greatest chance of benefiting from them. More important, urinalysis assists in distinguishing urinary tract infections and bladder cancer from BPH. These conditions may produce urinary tract symptoms (such as frequency and urgency) that mimic BPH.

The positive predictive value of urinalysis for cancer or other urologic diseases is 4 to 26 percent, depending on the patients screened and the rigor of followup studies (Mohr, Offord, Owen, et al., 1986 ; Mohr, Offord, and Melton, 1987 ; Messing, Young, and Hunt, 1987). If a dipstick approach is used, a test that includes leukocyte esterase and nitrite tests for the detection of pyuria and bacteriuria should be utilized (Preventive Services Task Force, 1989).

Creatinine Measurement (Assessment of Renal Function)

Measurement of serum creatinine is recommended in all patients with symptoms of prostatism.

There are many reasons for recommending creatinine measurement. One is the percentage of BPH patients who may have renal insufficiency. The panel's data base of BPH treatment arms contains seven studies in which the percentage of patients with renal insufficiency is mentioned (Attachment C). In these studies, the percentage of patients with renal insufficiency ranges from 0.3 to 30 percent. The mean is 13.6 percent. This may be an overestimation because the reports contain information only on patients eventually receiving treatment. Still, the number of patients with renal insufficiency, in a population of patients seeing a physician for symptomatic prostatism, may be as high as 1 in 10.

It is well established that BPH patients with renal insufficiency have increased risk for postoperative complications. The risk is 25 percent for patients with renal insufficiency, compared with 17 percent for patients without the condition (Mebust, Holtgrewe, Cockett, et al., 1989). Moreover, the mortality increases up to sixfold for BPH patients treated surgically if they have renal insufficiency (Holtgrewe, and Valk, 1962 ; Melchior, Valk, Foret, et al., 1974b). Of 6,102 patients evaluated in 25 studies by intravenous urography prior to prostate surgery, 7.6 percent had evidence of hydronephrosis. Of these patients, 33.6 percent had associated renal insufficiency.

Elevated serum creatinine in a patient is a reason for recommending appropriate imaging studies to evaluate the upper urinary tract. In a retrospective analysis of 345 patients who had undergone prostatectomy, 1.7 percent (n = 6) had occult and progressive renal damage (Mukamel, Nissenkorn, Boner, et al., 1979). These patients had minimal or no urinary symptoms and presumably fit the category of patients with "silent prostatism." Measurement of serum creatinine is one modality to identify such patients. Although renal insufficiency from minimally symptomatic BPH is probably rare, the probability has yet to be defined. Meanwhile, routine creatinine measurement is reasonable.

Prostate-Specific Antigen

Measurement of serum PSA is an optional test in men with prostatism.

Measurement of the serum PSA, in combination with the DRE, increases the detection rate of prostate cancer over DRE alone. However, a policy mandating the measurement of serum PSA cannot be issued because of (1) the significant overlap in PSA values between men with BPH and men with pathologically organ-confined cancer, (2) a lack of consensus concerning the optimal evaluation of minimally elevated PSA[sub s], and (3) a lack of evidence showing that PSA testing reduces the morbidity or mortality of men with prostatic disease.

Background

In the early 1970s, reports identifying prostate-specific antigens were first published by Ablin, Soans, Bronson, et al. (1970) and Hara, Inorre, and Fukuyama, (1971). The same antigen was isolated from prostatic tissue, purified, and demonstrated to be specific for prostatic tissue (Wang, Valenzuela, Murphy, et al., 1979-80). Although identified in all types of prostatic tissue (normal, benign hyperplastic, and malignant), it could not be found in any other human tissue. Thus, it became known as prostate-specific antigen.

PSA is a glycoprotein with kallikrein-like serine protease activity produced by the epithelial cells that line the acini and ducts of the prostate gland. PSA is secreted into the prostatic ductal system and causes liquefaction of the seminal coagulum at the time of ejaculation.

Concentrations of PSA per gram of tissue do not differ significantly among normal, hyperplastic, and cancerous prostate tissue. PSA can be detected in the serum of young men with small, nonhyperplastic prostates, older men with BPH, and men with localized or metastatic prostate cancer. For the individual with no prostatic disease (prostatitis, BPH, or prostate cancer), the serum concentration is extremely low. It has recently been demonstrated that the mean serum value for such a patient is 0.07+/-0.4 ng/mL (Glenski, Klee, Bergstrahl, et al., 1992). This is markedly lower than the upper limit of the reference range (4.0 ng/mL) by either the Tandem-R PSA assay or the IMx PSA assay (Oesterling, 1991).

For PSA to enter the general circulation, it must pass through a number of physiologic barriers, including the basal cell layer, the basement membrane of the acini, the prostatic stroma, the capillary basement membrane, and the capillary endothelial cells. Breakdown of these barriers, allowing serum PSA concentration to increase, may be caused by a number of conditions. They include prostatic infarction (a common phenomenon associated with acute urinary retention), prostatitis, BPH, and prostate cancer. Thus, an elevated serum PSA level is not pathognomonic for prostate cancer.

Agents and Procedures Affecting PSA Levels

The serum PSA level is affected by the new drug finasteride. Finasteride therapy for BPH reduces serum PSA by approximately 50 percent. Whether longitudinal followup of the serum PSA will have, for men on finasteride, the same diagnostic value as in the general population remains unclear. (Theoretically, differential suppression of PSA in men with BPH and prostate cancer could actually increase the information value of PSA measurements after treatment with finasteride.) If the patient and the physician elect to include PSA measurement in the initial BPH evaluation, a baseline should be reestablished after beginning finasteride.

Prostatic biopsy, surgery, and urethrocystoscopy can temporarily elevate the serum PSA level. It had been speculated that manipulation of the prostate during DRE might also raise the serum PSA level. However, in a multicenter study of 2,754 healthy men age 40 years and older (Crawford, Schutz, Clejan, et al., 1992), the increase observed after a DRE was not clinically or statistically significant for men with a serum PSA level <10.0 ng/mL (n = 2,667). For men with PSA values >10.0 ng/mL, a trend toward increased serum PSA levels was noted. At these already high levels, the increase would not interfere with clinical management.

Chybowski, Bergstralh, and Oesterling (1992), in the only prospective randomized study examining this issue, also found that a DRE does not have a clinically significant effect on serum PSA concentration. The median increase following a DRE was 0.4 ng/mL. For the majority of patients, such a minimal increase would not alter clinical management. Unlike for prostatic acid phosphatase, physicians do not have to obtain a serum PSA level before performing a DRE. Neither do they have to wait a period of time after the DRE to allow the serum PSA concentration to return to baseline before measuring the serum PSA level.

Serum PSA Levels and BPH

A significant percentage of men with histologically proven BPH have an elevated serum PSA level >4.0 ng/mL. Table 1 summarizes the findings of four major investigations with respect to the association between BPH and serum PSA.

Table 1. Serum PSA concentration in patients with histologically confirmed BPH [1].

Table

Table 1. Serum PSA concentration in patients with histologically confirmed BPH [1].

Other studies confirm the association between BPH and elevated serum PSA levels. Stamey, Yang, Hay, et al. (1987) used the Pros-Check PSA assay (Yang Laboratories, Bellevue, WA) to evaluate 73 patients with BPH and found 86 percent to have an elevated serum PSA level. The preoperative values ranged from 0.3 to 37 ng/mL, with the mean level being 7.9 ng/mL. After TURP, the mean value decreased to 1.3 ng/mL, with the range being 0.1 to 6.7 ng/mL. Based on these findings, the investigators concluded that benign hyperplastic tissue elevates the serum PSA level at a rate of 0.3 ng/mL per gram of BPH tissue (0.2 ng/mL by the Tandem-R PSA assay).

Daver, Soret, Coblentz, et al. (1988) found elevated PSA levels in 68 percent and 70 percent, respectively, of clinically and histologically confirmed BPH patients (n = 150). Another study (Buamah, Johnson, and Skillen, 1988), using the Tandem-R PSA assay with an established upper limit of normal of 5 ng/mL, found that 21 of 45 patients (47 percent) with histologically proven BPH had an elevated serum PSA level. Filella, Molina, Jo, et al. (1990), also utilizing the Tandem-R PSA assay, found that 87 percent of patients with BPH had PSA levels greater than 2 ng/mL; 13 percent had levels greater than 10 ng/mL.

Distinguishing Prostate Cancer from BPH

To be a valuable detector of early prostate cancer in patients with symptoms of prostatism, a PSA test must be able to identify and distinguish curable cancer from purely benign conditions of the prostate. In other words, a PSA test must have high sensitivity and specificity, low false-negative and false-positive rates, and high negative and positive predictive values.

Because BPH tissue contributes to the serum PSA concentration and has a high prevalence among men age 50 and over, one way to evaluate the serum PSA value as a reliable detector of early, curable prostate cancer is to compare serum PSA values in men with organ-confined prostate cancer (patients who have the greatest likelihood of cure from definitive therapy) with serum PSA values in men who have BPH only. Table 2 summarizes the serum PSA values for these two groups of patients, as determined from three major investigations published in the urologic literature.

Table 2. Comparative PSA values for BPH and organ-confined prostate cancer [1, 2].

Table

Table 2. Comparative PSA values for BPH and organ-confined prostate cancer [1, 2].

Pooling data from the three studies, Table 2 shows that, of patients with organ-confined prostate cancer, 43 percent (136 of 319) have a PSA value within the normal range (0.0 to 4.0 ng/mL). Of men with BPH, 25 percent (148 of 597) have a PSA value above 4.0 ng/mL.

Further analysis of the data (Table 3) demonstrates mediocre sensitivity and specificity for PSA when the values are between 4 and 10 ng/mL. The false positive rate is significant. However, true positive and negative predictive values cannot be calculated from these data because the ratio here between cancer and BPH cases is artificially high.

Table 3. Ability of PSA to distinguish organ-confined prostate cancer from BPH, based on data in Table 2.

Table

Table 3. Ability of PSA to distinguish organ-confined prostate cancer from BPH, based on data in Table 2.

Comparing the individual serum PSA values for men who have BPH with the values for patients who have organ-confined prostate cancer, Partin, Carter, Chan, et al. (1990) found no statistically significant difference between the two groups. The mean value (+/- standard error) for men with BPH was 5.98+/-1.0 ng/mL, whereas the mean level for the patients with organ-confined prostate cancer was 5.62+/-0.6 ng/mL. Similar results are obtained when clinical stage A and B prostate cancer patients are compared with men who have BPH (Chan, Bruzek, Oesterling, et al., 1987). These findings indicate that serum PSA concentration does not have either the sensitivity or the specificity of an ideal detector. On an individual basis, serum PSA is not a reliable test for distinguishing men with BPH from patients with early prostate cancer.

Serum PSA Compared with DRE

Recently, two large-scale studies have been conducted examining the role of PSA as a screening test for prostate cancer (Catalona, Smith, Ratliff, et al., 1991 ; Brawer, Chetner, Beatie, et al., 1992). At Washington University in St. Louis, Missouri, Catalona and associates evaluated 1,653 healthy, asymptomatic men who had a serum PSA concentration; 37 of the men were diagnosed with cancer, for an overall detection rate of 2.2 percent. At the University of Washington in Seattle, Brawer and colleagues had a detection rate of 2.6 percent in a study of 1,249 men. These values are somewhat better than the 1.3 to 1.5 percent reported for DRE by Cupp and Oesterling (1993).

In the St. Louis study, 32 percent of the cancers identified would have been missed if DRE alone had been used. The Seattle group found that 38 percent of cancers in their study population would not have been identified if DRE alone had been used. From these studies, it appears that measurement of the PSA level can identify prostate cancer not detectable by DRE (impalpable lesions) and that, for a given population, PSA measurements can identify 50 to 61 percent more prostate cancers than can DRE.

However, DRE has also been shown to detect prostate cancers not identifiable by an elevated serum PSA concentration. Catalona, Smith, Ratliff, et al. (1991) examined 300 men who underwent prostate biopsy for various reasons, but not necessarily because of an elevated serum PSA value. They found that 21 percent of the patients with biopsy-proven cancer had a serum PSA value in the reference range (0.0 to 3.9 ng/mL, using the Tandem-R PSA assay) and would have been missed if the decision to take a biopsy specimen were made on the basis of PSA level alone. Cooner, Mosley, Rutherford, et al. (1990), evaluating over 1,800 patients presenting to a urologic practice, made very similar observations.

These data suggest (1) that PSA measurements cannot identify all detectable cancers and (2) that DRE can detect lesions that would be missed by relying on the serum PSA concentration alone. All the studies taken together indicate that the most sensitive test strategy for prostate cancer is use of both DRE and serum PSA measurements. Some cancers are identified by DRE, some by serum PSA. They are not necessarily the same lesions.

PSA Velocity and PSA Density

The ability of serum PSA measurement to detect prostate cancer at an early, curable stage and distinguish it from BPH was examined further by Carter, Pearson, Metter, et al. (1992). Carter and associates investigated the concept of "PSA velocity," the rate of change in serum PSA. In a unique study based on banked serum from the Baltimore Longitudinal Study of Aging (BLSA), they demonstrated that the rate of change was more useful than the actual serum PSA level for detecting prostate cancer. When a cutoff of 0.75 ng/mL or higher per year for the rate of change was used, the specificity was 90 percent as compared with 60 percent for the cutoff of 4.0 ng/mL or higher for the serum PSA concentration. The sensitivity for the rate of change, however, was not significantly better than for the serum PSA concentration. The number of cancer patients studied was small (n = 20). The validity of PSA velocity needs further prospective evaluation.

Another technique for improving PSA's ability to detect early prostate cancer is to correlate the serum PSA concentration with the prostatic volume. A mildly elevated serum PSA level associated with a small prostate gland may be indicative of cancer, whereas the same value in a patient with a large gland may be only indicative of BPH.

To investigate this concept, Benson and associates (Benson, Whang, Olsson, et al., 1992 ; Benson, Whang, Pantuck, et al., 1992) defined the parameter of "PSA density." PSA density is a quotient, the serum PSA concentration divided by the volume of the prostate gland as determined by transrectal ultrasonography. The investigators found this parameter useful for distinguishing men with BPH from patients with prostate cancer, especially when the serum PSA value is between 4 ng/mL and 10 ng/mL and the DRE is negative. Patients with values in this "mildly elevated range" who also have an elevated PSA density may be at increased risk for having prostate cancer. Patients with PSA values in the same range, but with a low PSA density, are unlikely to harbor a malignancy in the prostate.

PSA density may become a useful tool to help physicians decide which patients with an intermediate PSA level should undergo prostate biopsy and which to follow with annual evaluation. Other studies are underway. Currently, however, the panel is unable to validate the predictive value of PSA density. Like PSA velocity, PSA density requires further investigation before it can be recommended as a valid diagnostic test.

Impact of PSA Testing on Ultimate Outcomes

When the role of PSA in the diagnostic workup of patients with BPH is evaluated, a key question is how many of the approximately 10 to 15 percent of patients found to have stage A1 or A2 prostate cancer at the time of TURP would be detected prior to surgery. Some of these men might be approached differently if a preoperative evaluation uncovered an impalpable prostate cancer.

Although most of this discussion has focused on the accuracy of PSA testing, a more important issue is that the value of early prostate cancer detection itself is controversial. Unfortunately, no data are available to establish that earlier diagnosis leads to decreased morbidity or mortality. The average age of patients undergoing surgical treatment of BPH is 67 years. Therefore a substantial number of men presenting with prostatism will be over 70, when the value of aggressive treatment with radical prostatectomy or radiation therapy is subject to question even by advocates of early detection and treatment.

Several large-scale investigations are underway to address these issues. Until this information becomes available, it is reasonable that a serum PSA determination be considered an optional diagnostic test in evaluating men presenting with prostatism. PSA determination would presumably be of most value in those men for whom the diagnosis of nonpalpable prostate cancer would change the BPH treatment recommendation.

Views

  • PubReader
  • Print View
  • Cite this Page

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...