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  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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Benign Prostatic Hyperplasia: Diagnosis and Treatment.

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9 Direct Treatment Outcomes— Symptom Improvement

The probability of symptom improvement, as well as the magnitude of that improvement, is greater for surgical treatment modalities than for nonsurgical treatment options. There is a large degree of uncertainty, based on reported data, regarding the probability of symptom improvement following alpha blocker therapy and balloon dilation, which may be due to the limited number of patients studied and widely varying data among studies. All active treatment modalities are superior in regard to probability of symptom improvement when compared with watchful waiting in short-term studies.

Probability of Symptom Improvement

BPH is characterized by a constellation of symptoms usually referred to as "prostatism." For the vast majority of patients, these symptoms are the dominant aspect of the disease and the motivating factor in seeking medical attention. More than 90 percent of all surgical procedures performed for BPH in the United States are done for symptoms or a combination of symptoms and other indications (Mebust, Holtgrewe, Cockett, et al., 1989). Of all the direct health outcomes in these analyses, symptom improvement is of greatest concern to the patient.

The typical symptoms of prostatism are classically divided into obstructive and irritative symptoms, and certain treatments might alter one set of symptoms more than another. Quantification of symptoms by symptom score assessment (see chapter 4) is a fairly new development and has not been utilized extensively in the literature. Therefore, in analyzing the response of symptoms to treatment, two different response measures have to be considered: (1) the probability of a given patient's improving symptomatically following treatment, based on global subjective assessment by either the patient or his physician, and (2) the degree of symptomatic improvement as measured by a standardized symptom score.

The nonuniform, subjective nature of global assessments of symptom status by either patients or physicians is problematic, but in many studies this is the only symptom-related outcome reported. Many other studies do not report information on symptom change in response to treatment. In the BPH reference data base, symptom-change information is reported for 7.4 percent of all TURP patients in the data base (n = 58,095) and 4.8 percent of all open surgery patients (n = 25,678).

Even after excluding the largest retrospective study contained in the data base (Roos, Wennberg, Malenka, et al., 1989), which focuses principally on long-term mortality and reoperation rates after TURP (n = 39,077) and open surgery (n = 14,087), only 22.6 percent of all TURP patients and 10.6 percent of open surgery patients reported symptom data. Only a small fraction of the studies report symptom change utilizing a quantitative scoring system.

Despite the lack of uniformity in reporting, three categories of changes in symptom status can generally be identified in published reports: "improved," "unchanged," and "worse."

About 40 percent of patients reported global improvement after placebo treatment, and the same percentage reported improvement during or following watchful waiting (Figure 6). More than one-third of patients actually experienced deterioration under a watchful waiting strategy, as opposed to placebo treatment where most of the remaining patients reported their symptoms unchanged. These findings may result from the short duration of the placebo trials, a different threshold for patients receiving placebo to report symptom deterioration, and selection of patients for placebo trials who were less symptomatic than watchful waiting patients.

Figure 6. Percentage of patients experiencing changes in globally assessed BPH symptom status following treatment.

Figure

Figure 6. Percentage of patients experiencing changes in globally assessed BPH symptom status following treatment.

All "active" treatment modalities have a higher rate of patients reporting global subjective symptom improvement, which is particularly true for the TUIP, TURP, and open surgery treatment options. Even assuming a higher subjective success rate because of patient expectations based on the invasiveness of the procedure, the doubling of the number of patients reporting improvement after surgery, compared with placebo treatment arms of drug studies, confirms the effectiveness of these treatment modalities. It should also be noted that the success rates for TUIP and TURP are virtually identical.

The reported global subjective symptom improvement probabilities were subjected to a confidence profile analysis using the hierarchical Bayes' model. The analysis was structured as a dichotomous outcome where the two choices were either improvement or no improvement (Table 13). As evidenced by the wide 90-percent CIs, considerable uncertainty exists regarding the symptomatic outcome following especially placebo treatment and balloon dilation. This uncertainty may be based on the limited number of patients reported (as for balloon dilation) or on the widely varying data among studies reported (as for placebo treatment).

Table 13. Median probability for symptom improvement.

Table

Table 13. Median probability for symptom improvement.

The CIs for TUIP and for open surgery are rather narrow, indicating some degree of certainty about their symptomatic outcomes. The CI for TURP is somewhat wider but allows reasonable confidence about the true magnitude of the effect. The CI for finasteride is relatively small because of the large number of patients studied.

Magnitude of Symptom Improvement

In addition to the overall probability of improvement, the magnitude of improvement is important. For example, two therapies may have a similar likelihood of improvement, but one may produce a more substantial decrease in symptom severity as quantified by a symptom scoring system (see chapter 4).

In the studies reviewed, a symptom score was reported in eight placebo arms, three balloon dilation and three alpha blocker arms, two finasteride arms (5-mg dose), four TUIP and TURP arms, and one open surgery series, thus complicating the comparison. Moreover, in some studies the investigators created their own scoring system or modified an existing system. No watchful waiting study reported symptom score effects.

Because all scores attempt to achieve the same goal -- capturing the sum of all BPH-related symptoms in a number -- the available data were combined. The total achievable score in each series was considered 100 percent. The mean pretreatment and posttreatment scores were calculated as percentages of the total score, and the percent drop in score was calculated ([Score[pre] - Score[post]] X 100/Score[pre] = percent improvement in score).

The panel believes there are sufficient data to confirm a short-term symptom improvement with alpha blockers, finasteride, and balloon dilation compared with placebo, as well as a clearly superior benefit of surgery over the alternative therapies. However, a variety of methodological problems prevent any determination of relative efficacy between the surgical procedures and between the less invasive therapies.

Two additional general caveats pertaining to the analysis are: (1) no watchful waiting series has reported symptom scores and therefore no information is available for this management option; (2) the only series reporting a symptom score before and after open surgery for BPH is limited in number (12 subjects), and the authors created their own symptom score with a total achievable score of 12 points (Castro, Griffiths, and Edwards, 1971). Data presented on open surgery must therefore be viewed with caution.

Surgery and Balloon Dilation

The three surgical treatment modalities (TUIP, TURP, and open surgery) achieved a greater improvement in symptom score, both individually and when combined (Figure 7), and a significantly larger drop in the score than was seen with less invasive treatments. It should be emphasized that the three studies on balloon dilation are homogeneous in regard to the symptom score results, although different techniques and different balloon devices were used by the investigators. It remains to be proven whether the drop in the symptom score after balloon dilation will come closer to the drop following TURP if the patients for balloon dilation are carefully selected: for example, no middle lobe, gland <30 grams, and mainly lateral lobe hyperplasia. Not enough information is currently available to answer this question conclusively. A recently published, small controlled trial of balloon dilation compared with TURP suggested similar initial improvement, followed by gradual increase in symptom scores in the dilation group after 3 months (Donatucci, Donohue, Berger, et al., 1993).

Figure 7. Percent improvement in symptom score following different BPH treatments.

Figure

Figure 7. Percent improvement in symptom score following different BPH treatments.

Alpha Blockers

The three studies using selective alpha-1 receptor blockers are also homogeneous in their outcomes regarding symptom score changes. The starting mean pretreatment score was only 34.4 percent of the total achievable score in these studies. The mean drop in score was 16.5 percent to 17.9 percent of the total achievable score, not much greater than for placebo (14.5 percent). Yet, because the alpha blocker studies started at a lower pretreatment score than did the placebo arms (34.4 percent compared with 44.7 percent), the mean improvement in score expressed in percent (see Figure 7) appears larger (48 percent compared with 32 percent). Because the patient population in the alpha blocker studies appears to have less severe symptomatology than do the patients in the surgical treatment arms, direct comparisons may not be accurate. A recently published controlled trial of terazosin (which was not in the combined analysis) demonstrated a 23-percent improvement in the symptom score in the placebo group compared with a 33-percent improvement in patients treated with 5 or 10 mg of terazosin (Lepor, Auerbach, Puras-Baez, et al., 1992).

Finasteride

In contrast to most studies, the North American and international phase III finasteride trials (Gormley, Stoner, Bruskewitz, et al., 1992 ; Finasteride Study Group, 1993) obtained the baseline score after a 2-week placebo run-in phase during which the score had already decreased in both the placebo and the drug-treated groups. Furthermore, many patients with low symptom severity were entered into the finasteride studies, thus limiting the ability to show a substantial decrease in the total score. In patients whose symptoms were "mild," it was not possible to demonstrate a substantial decrease in the symptom score from baseline with finasteride.

As with other studies of BPH treatment, the higher the baseline score, the more dramatic the reductions noted in the score in both the finasteride and the placebo-treated arms. The 5-mg finasteride-treated patients with "severe" symptoms in the phase III studies had a decrease in their baseline score by about 6.5 and 7.5 points in the North American and international trials respectively, representing an 18- to 21-percent drop in the total achievable score. The difference between patients treated with the active drug and placebo-treated patients was also larger in the "severe" symptom subgroup.

For finasteride, the maximum effect on the symptom score was achieved between 6 and 12 months and maintained over a 24-month followup in the open extension study (5 mg of finasteride). Overall, 63 percent (North American trials) and 71 percent (international trials) of patients treated with 5 mg of finasteride rated their symptoms "improved," compared with 51 percent and 60 percent of placebo-treated patients, respectively.

In these studies, the total symptom score dropped with finasteride (at 5 mg daily) from 10.1 to 7.5 points (or 28.05 to 20.8, drop = 7.25, linearly transformed to a 100-point scale) in the North American trials, and from 10.6 to 6.7 points (or 29.4 to 18.6, drop = 10.8, on a 100-point scale) in the international trials. The placebo-treated patients in both these studies experienced a drop from 10.1 to 9.1 points (or 28.05 to 25.3, drop = 2.75) in the North American trials, and from 10.6 to 8.0 points (or 29.4 to 22.2, drop = 7.2) in the international trials. These changes represent a reduction in symptom score of 26 percent and 37 percent for the finasteride-treated groups and of 10 percent and 25 percent for the placebo-treated groups (North American, and international studies, respectively).

Conclusions

Given the varying methods of symptom analysis among the different studies examined, the relatively small differences between balloon dilation, alpha blockers, and finasteride should not be overinterpreted. Only a controlled study directly comparing those treatments in a randomized fashion with standardized symptom assessments would resolve the issues. More important, the durability of the responses is uncertain as these studies were relatively short. Clearly, however, surgical options have the highest probability of symptom improvement as well as the highest degree of symptom improvement.

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