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Keywords:

  • benign prostatic hyperplasia (BPH);
  • I-PSS;
  • Qmax;
  • QOL index;
  • tamsulosin;
  • transfer to invasive therapy

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Abstract  Three hundred Japanese patients with benign prostatic hyperplasia (BPH) who started an α1-adrenoceptor blocker, tamsulosin, between 1993 and 1996 were followed for 3.0 ± 3.3 years (mean ± SD) to determine whether an association existed between the disease severities measured prior to the tamsulosin treatment and the timing at which the invasive therapy was implemented. Patients with a lower quality of life (QOL) index or maximum urinary flow rate (Qmax) were transferred for invasive therapy earlier than those with less severe BPH. The International Prostate Symptom Score (I-PSS) was also associated, but apparently to a lesser extent, with the timing of the invasive therapy. Finally, the overall severity evaluated using all of the above three indices, I-PSS, QOL index, and Qmax, in accordance with the ‘Severity Criteria for BPH’ issued by the Japanese Urological Association, was found to be a good measure for predicting the prognosis of patients with BPH treated with tamsulosin.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

The most common medical treatment for patients with benign prostatic hyperplasia (BPH) involves α1-adrenoceptor blockers. Tamsulosin, a selective α1-adrenoceptor blocker, has been widely used in various countries including Japan, while few studies have so far studied the patients treated by tamsulosin for a long time period.1–3 Several indices, including the International Prostate Symptom Score (I-PSS), quality of life (QOL) index, and maximum urinary flow rate (Qmax), are currently used in evaluating the severity of BPH to select the most appropriate treatment for BPH. However, none of these parameters taken singly is a sufficient indicator to preselect the patients who could continue the drug therapy without surgical intervention. The ‘Severity Criteria for BPH’, issued by the Japanese Urological Association, recommends a drug therapy when the ‘overall severity’ rating remains mild or moderate. In this study, we followed patients with BPH who had undergone tamsulosin treatment for years, to determine whether an association existed between the disease severities measured prior to the tamsulosin treatment and the timing at which the invasive therapy was implemented.

Subjects and methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

During the period between 1993 and 1996, a total of 300 patients with BPH were evaluated in a systematic manner before tamsulosin monotherapy was started. In this study, the investigators recorded the values of I-PSS, QOL index, and Qmax measured before the drug treatment in this retrospective long-term study group from 21 medical institutions in Japan. The patients were then followed until they underwent invasive therapy. The study period ended in May 2004 or the patient was lost to follow up. Some patients were followed up after the cessation of drug administration.

Survival analysis was performed using a log–rank test to determine whether an association existed between the disease severities measured prior to the tamsulosin treatment and the timing at which the invasive therapy was implemented. The significance level was set at 0.05 for a two-sided test. The severity of BPH was classified according to the I-PSS, QOL index, or Qmax as defined in Table 1, as well as the ‘overall severity’ as defined in Table 2.

Table 1.  Criteria for individual severity in benign prostatic hyperplasia
  1. I-PSS, international prostate symptom score; Qmax, maximum urinary flow rate; QOL, quality of life.

I-PSS
 Mild 0–7
 Moderate 8–19
 Severe20–35
QOL index
 Mild0, 1
 Moderate2–4
 Severe5, 6
Qmax
 Mild≥15 mL/s
 Moderate≥5 mL/s
 Severe<5 mL/s
Table 2.  Criteria for overall severity in benign prostatic hyperplasia
Overall severityNumber of evaluation items estimated as
MildModerateSevere
  1. Modified ‘Severity Criteria for BPH’ issued by Japanese Urological Association. BPH, benign prostatic hyperplasia.

Mild3 0 0
2 1 0
ModerateAny≥2 0
AnyAny 1
SevereAnyAny≥2

The criteria shown in Table 2 are according to, but not exactly the same as, the ‘Severity Criteria for BPH’, because the criteria require the use of data for residual urine volume, prostate volume, I-PSS, QOL index, and Qmax,4,5 while only the last three of these were available in the current study.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

The average age at which the patient started tamsulosin treatment was 68.5 ± 8.1 years old (mean ± SD; range 42–90). Table 3 shows the distribution of I-PSS, QOL index, and Qmax measured prior to tamsulosin treatment. When using the overall severity defined in Table 2, the levels of the severity for 2 (0.7%), 202 (67.3%), 63 (21.0%), and 33 (11.0%) patients were classified to be mild, moderate, severe, and unspecified, respectively. The mean age of 204 (2 + 202) patients with mild/moderate disease was 68.1 years, and similarly 69.0 years in 63 patients with severe disease and 69.8 years in 33 patients with undetermined severity.

Table 3.  The international prostate symptom score (I-PSS), quality of life (QOL) index, and maximum urinary flow rate (Qmax) at baseline
 Overall severity
Mild/moderateSevereUnspecifiedTotal
ValueNValueNValueNValueN
  1. SD, standard deviation.

I-PSS
  204 63 29 296
 Mean13.3 24.6 19.3 16.3 
 SD 4.6  5.2  6.1  6.8 
 Range(2, 27) (11, 35) (6, 31) (2, 35) 
 Missing  0  0  4  4
QOL index
 0  1  0  0  1
 1  3  0  1  4
 2  11  0  0  11
 3  31  1  0  32
 4  71  2  0  73
 5  36 33  0  69
 6  9 21  1  31
 Missing  42  6 31  79
Qmax (mL/s)
  202 61 22 285
 Mean 9.6  7.2  7.9  8.9 
 SD 3.7  3.7  5.2  4.0 
 Range(1.9, 26.6) (2.4, 20.0) (1.2, 21.0) (1.2, 26.6) 
 missing  2  2 11  15
 Total 204 63 33 300

The mean follow-up period was 3.3 years in the patients with mild/moderate disease, longer than the 2.0 years in those with severe disease. Similarly, the mean duration of tamsulosin treatment, 2.5 years in the patients with mild/moderate disease, was longer than the 1.6 years for those with severe disease (Table 4). This difference was observed mainly because the follow-up and treatment periods were shorter in the patients with more severe disease who underwent invasive treatment than in those with less severe disease. For example, 25 of 63 severe patients had received tamsulosin for an average of 0.6 years and then an invasive treatment, on average, 1.0 years after they started tamsulosin. On the other hand, 45 of 203 mild/moderate patients had received tamsulosin for an average of 1.0 years and then an invasive treatment, on average, 2.2 years after they started tamsulosin.

Table 4.  Mean follow-up period and mean duration of tamsulosin therapy in the observation period
Overall severityNMeanSDMinMax
  • Excluding the patient discontinued on an unknown data. SD, standard deviation.

Mean follow-up period (years)
Mild/moderate2043.33.40.09.8
Severe 632.02.90.09.4
Unspecified 333.53.10.09.2
Total3003.03.30.09.8
Mean duration of tamsulosin therapy in the observation period (years)
Mild/moderate2032.53.00.09.1
Severe 631.62.60.09.3
Unspecified 332.93.00.09.2
Total2992.42.90.09.3

Of the 63 patients classified with severe disease, the starting dose of tamsulosin was 0.2 mg/day in all but one patient, who used 0.1 mg/day. Of the 204 patients with mild/moderate disease, the starting dose was 0.2 mg/day in 191 patients, and 0.1 mg/day in 13 patients. The starting dose was 0.2 mg in all of the 33 patients with undetermined severity.

After tamsulosin was started, 83 (27.7%) of the 300 patients eventually had the invasive treatment. Three patients suffered from urinary retention. Of the 83 patients with the invasive treatment, 61 (73%) had transurethral resection of the prostate (TURP) or transurethral incision of the prostate (TUIP), 8 (10%) had open operation, 6 (7%) had laser treatment, 4 (4%) had thermotherapy, and the remaining 4 (4%) had other therapies (Table 5).

Table 5.  Details of the initial invasive treatment
 Incidence of the event = 0.277 (= 83/300)
TURP/TUIPLaserThermo-therapyOpen operationOthersTotal
  1. TURP, transurethral resection of the prostate; TUIP, transurethral incision of the prostate.

Mild/moderate33334245
Severe17214125
Unspecified11100113
Total61648483

The results of the Kaplan–Meier plots are shown in Figures 1–3. When rated by I-PSS, QOL index, and Qmax, the survival curve profiles differ among patient groups with differing severity, and the patients with the less severe disease were free from the invasive therapy for longer periods than those with the severe disease. The strength of association was the most remarkable when classified by Qmax (P < 0.001; Fig. 1), followed by QOL index (P = 0.007; Fig. 2), and I-PSS (P = 0.063; Fig. 3). Figure 4 shows the Kaplan-Meier plot when the severity of the disease was classified according to the overall severity criteria given in Table 2. When the severity was rated by this definition, 25% of severe patients had the invasive therapy within 0.31 years (3.7 months) after the tamsulosin treatment, while it took 3.15 years when the severity was rated as mild/moderate (P < 0.001).

image

Figure 1. Kaplan–Meier plot classified by maximum urinary flow rate (Qmax). P < 0.001, log–rank test.

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image

Figure 2. Kaplan–Meier plot classified by quality of life (QOL) index. P = 0.007, log–rank test.

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image

Figure 3. Kaplan–Meier plot classified by international prostate symptom score (I-PSS). P = 0.063, log–rank test.

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image

Figure 4. Kaplan–Meier plot classified by overall severity. P < 0.001, log–rank test.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

In this study on 300 Japanese patients treated with tamsulosin for BPH, the baseline severity was significantly associated with the timing when the patient eventually had the invasive treatment. The survival curve profiles differ among patient groups with differing severity defined by overall (P < 0.001), I-PSS (P = 0.063), QOL (P = 0.007), or Qmax (P < 0.001) values. It is difficult to evaluate which criterion is the best; though Qmax seems to be the most efficient in predicting the outcome (Fig. 1), up to a quarter of patients with the unspecified severity due to missing data (Table 3) as well as a paucity of mild patients preclude a conclusive assessment, particularly for the overall severity (Fig. 4). Our finding was slightly different from the previous study by Ichioka et al.,3 in which the baseline I-PSS and QOL score, but not Qmax, were found to be significant risk factors. The reason for this discrepancy is not clear. However, one possible explanation would be that 123 patients studied by Ichioka et al.3 had been treated with tamsulosin for periods longer than 12 months before they were enrolled in the study, while our 300 patients were observed immediately after they started tamsulosin. Indeed, 25% of severe patients had the invasive therapy within 0.31 years (3.7 months) after the tamsulosin treatment.

In the study by de la Rosette et al.,6 the re-treatment rate up to 3 years of follow up was 27, 37, and 49% in the patients with tamsulosin, alfuzosin, and terazosin treatment, respectively. This was similar to the results of the current study, in which 25% of patients classified with mild/moderate severity had the invasive therapy up to 3.15 years after starting tamsulosin; however, the effect of tamsulosin could not be precisely evaluated in the current study due to a lack of control patients. Prospective controlled randomized studies utilizing the indices including prostatic size and residual volume in addition to I-PSS, QOL index, and Qmax could produce more accurate results than were obtained in this study. A prospective study on patients with various severities is also desirable in order to fully assess the usefulness of the overall severity, which could be better defined if the data for all of the indices are available.5

In conclusion, the severity of BPH measured by I-PSS, Qmax, or QOL index, together with the ‘overall severity’ estimated from those three indices, can be used to predict the timing of the invasive therapy and may be useful in selecting appropriate treatment for patients with BPH.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References

Mr Yoshihiro Muraoka participated in all phases of this study as well as in the preparation of this paper. Mr Tsugumichi Sato and Ms Eri Kawabe assisted with the statistical analyses in this study.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Subjects and methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References