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Postvoid residual urine in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia: pooled analysis of eleven controlled studies with alfuzosin
ADULT UROLOGY
POSTVOID RESIDUAL URINE IN PATIENTS WITH LOWER URINARY TRACT SYMPTOMS SUGGESTIVE OF BENIGN PROSTATIC HYPERPLASIA: POOLED ANALYSIS OF ELEVEN CONTROLLED STUDIES WITH ALFUZOSIN S. ALAN MCNEILL, TIMOTHY B. HARGREAVE, CHRISTINE GEFFRIAUD-RICOUARD, JEAN-PHILIPPE SANTONI, AND CLAUS G. ROEHRBORN
ABSTRACT Objectives. A pooled analysis was conducted in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia to examine the relationship between the postvoid residual urine (PVR) volume and various clinical characteristics and to assess the effect of alfuzosin, a clinically uroselective alpha1blocker, on PVR volume and any other associated outcome. Methods. Nine hundred fifty-three patients, 42 to 89 years old, with a baseline PVR volume between 50 and 350 mL (mean 106 mL) were enrolled in 11 double-blind controlled studies and received either alfuzosin (n ⫽ 607) or placebo (n ⫽ 346) for 1 to 6 months. The relationships between the baseline PVR volume measured by transabdominal ultrasound and age, symptoms, maximum flow rate (Qmax), estimated bladder capacity, and prostate-specific antigen level were assessed. The changes in the PVR volume with treatment were evaluated in all available patients at three endpoints (1, 3, and 6 months). Results. At baseline, a PVR volume of 100 mL or greater was observed in 60%, 47%, and 39% of patients with a Qmax less than 8, 8 to 11, and greater than 11 mL/s, respectively (P ⫽ 0.001). The bladder capacity was also significantly related to the Qmax (P ⫽ 0.0001). No relationship was found between PVR volume and age, symptoms, or prostate-specific antigen level. The changes in the PVR volume with treatment were related to the baseline PVR volume. However, at all endpoints and whatever the baseline PVR volume, the decreases in the PVR volume were significantly (P ⬍0.01) greater with alfuzosin than with placebo. Acute urinary retention occurred in 7 patients (2 [0.3%] of 607 patients taking alfuzosin and 5 [1.4%] of 346 patients taking placebo); 6 of these 7 patients had a baseline PVR volume greater than 100 mL. Conclusions. In this population of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, the PVR volume and bladder capacity were related to the baseline Qmax. Alfuzosin significantly reduced the PVR volume compared with placebo, and this effect was more marked in patients with a high PVR volume at baseline. Acute urinary retention occurred mainly in patients with a PVR volume greater than 100 mL and was less frequent in patients taking alfuzosin than in those taking placebo. UROLOGY 57: 459–465, 2001. © 2001, Elsevier Science Inc.
M
easurement of the postvoid residual urine (PVR) volume using transabdominal ultrasound is recommended by the International Consultation on Benign Prostatic Hyperplasia (BPH) at
the initial assessment and at follow-up examinations of patients under watchful waiting or other conservative treatment regimens.1 The presence of a PVR volume in patients with BPH is commonly
There was no direct funding for this meta-analysis, but each included study was funded by Sanofi-Synthe´labo. S. A. McNeill, C. G. Roehrborn, and T. B. Hargreave are funded clinical investigators for Sanofi-Synthe´labo. From the Western General Hospital, Edinburgh, Scotland, United Kingdom; Sanofi-Synthe´labo, Paris, France; and University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
Reprint requests: S. Alan McNeill, M.D., Department of Urology, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, Scotland Submitted: July 26, 2000, accepted (with revisions): October 16, 2000
© 2001, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
0090-4295/01/$20.00 PII S0090-4295(00)01021-9 459
TABLE I. Description of randomized studies included in the pooled analysis
Study BPH-ALF9 MCE2 UDM1 ALFURO10 PRANALF11 PRAZALF12 XATTAD13 PERMALF14 DALBI15 ALGEBI16 ALFIN17 Total
Design Placebo-controlled Placebo-controlled Placebo-controlled Placebo-controlled Placebo-controlled vs. other drug Controlled vs. other drug Controlled vs. other drug Controlled vs. other drug Placebo-controlled Placebo-controlled Controlled vs. other drug
Main Inclusion Criteria Boyarsky Boyarsky Boyarsky Boyarsky Boyarsky
ⱖ6 ⱖ6 ⱖ6, Qmax 5–12 mL/s ⱖ6, Qmax 5–12 mL/s ⱖ9, Qmax ⱕ15 mL/s
Frequency, Qmax ⬍15 mL/s Frequency, Qmax 5–15 mL/s Frequency, Qmax ⬍15 mL/s Frequency, Qmax 5–12 mL/s Frequency, Qmax 5–15 mL/s IPSS ⬎7, Qmax 5–15 mL/s
Randomized Treatment Patients at Patients (n) Duration Baseline Alfuzosin Placebo (mo) (n) 160 48 40 25 73
74 21 18 10 24
86 27 22 15 24
61 172 20 118 215 538 1470
28 83 9 58 103 179 607
— — — 60 112 — 346
6 6 3 1 1 1 2* 1 1 3 6
KEY: Qmax ⫽ maximum urinary flow rate; IPSS ⫽ International Prostate Symptom Score. * For XATTAD study, the endpoint was considered at month 3 instead of month 2, which was the actual treatment duration.
associated with urodynamically proved bladder outlet obstruction. However, the usefulness of the PVR volume determination as a diagnostic test is still questioned, because no clear relationship has been found between the PVR volume and either the severity or the duration of outlet obstruction.2 In addition, the absence of a PVR volume does not rule out severe obstruction.3 This may in part be related to the large interindividual and intraindividual variability of this parameter, especially in those patients with a large PVR volume.4 Nevertheless, the presence of a large PVR volume remains a common indication for transurethral resection of the prostate.5 It may also predispose patients to the occurrence of serious BPH complications such as urinary tract infection,6 bladder calculi,7 and upper tract dilation with renal function impairment (especially in case of high detrusor pressure).3 In addition, clinical data collected from randomly selected men, 40 to 79 years old (all residents of Olmsted Country, Minn), suggest that men with a PVR volume greater than 50 mL are about three times more likely to develop acute urinary retention.8 We sought to determine the relationship between PVR and various clinical parameters such as age, lower urinary tract symptoms (LUTS), maximum flow rate (Qmax), estimated bladder capacity, and prostate-specific antigen (PSA) and to characterize the effect of alfuzosin, a clinically uroselective alpha1-blocker, on the PVR volume and any associated impact on outcome in a pooled analysis of 11 double-blind controlled studies of patients with LUTS suggestive of BPH. 460
MATERIAL AND METHODS The clinical data of 1470 patients with LUTS suggestive of BPH and a PVR volume between 50 and 350 mL at the time of study inclusion were pooled. These patients were enrolled in 11 European double-blind controlled studies with alfuzosin, which have been published as full reports or abstracts.9 –17 The design, entry criteria, and number of patients available for evaluation per visit for each trial are shown in Table I. Of these 1470 patients, 953 were randomly allocated to receive either alfuzosin (immediate-release formulation, 2.5 mg three times daily, n ⫽ 267; sustained-release formulation, 5 mg twice daily, n ⫽ 340; total n ⫽ 607) or placebo (n ⫽ 346) for 1 to 6 months, and 912 patients (alfuzosin group, n ⫽ 584; placebo group, n ⫽ 328) underwent an assessment of PVR volume after the baseline assessment. Both alfuzosin formulations were bioequivalent; a higher dosage was required for the twice daily formulation because of a loss of bioavailability of about 20% compared with the three times daily formulation. The remaining patients (n ⫽ 517) received various other agents (eg, Serenoa repens, Pygeum africanum, prazosin, or finasteride alone or in combination with alfuzosin). The baseline correlations between the PVR volume and various clinical parameters (age, LUTS, Qmax, estimated bladder capacity, and PSA) were assessed in the overall population (n ⫽ 1470). The analysis of the PVR volume changes with treatment was limited to the alfuzosin and placebo groups that were the most representative in terms of the number of patients. The PVR volume was determined by transabdominal ultrasound measurement performed immediately after the uroflowmetry recording. No particular formula was specified by the protocol, but investigators were requested to use the same formula for each patient. The bladder capacity was indirectly estimated by the sum of the voided volume (provided by the uroflowmeter) and the PVR volume measurement. LUTS were assessed in all studies using a modified Boyarsky score,9 which included seven items scored 0 to 3 in increasing order of severity (maximum theoretical score of 21). In the two most recent studies,16,17 LUTS were also assessed using the International Prostate Symptom Score questionnaire. All uroflowmetry curves were reviewed and validated by an expert unaware of the treatment assignment. A voided volume of at least 100 mL was required to consider a curve valid. PSA values UROLOGY 57 (3), 2001
TABLE II. Clinical characteristics of patients at study inclusion Overall Population (n ⴝ 1470)
Characteristic Age (yr) Symptom duration (mo) Boyarsky total score Qmax (mL/s) PVR volume (mL) No. of patients (%) with baseline PVR volume of 50–100 mL 100–150 mL ⱖ150 mL
64.5 39.5 9.5 9.8 106.1
⫾ ⫾ ⫾ ⫾ ⫾
7.4 (42–89) 34.0 (1–240) 2.6 (2–20) 4.0 (2–46) 54.5 (50–350)
748 (51) 439 (30) 283 (19)
KEY: Qmax ⫽ maximum urinary flow rate; PVR ⫽ postvoid residual (urine). Data presented as the mean ⫾ SD, with the range in parentheses, unless otherwise noted.
were measured at baseline in the three most recent studies.15–17
STATISTICAL ANALYSIS The PVR volume was described at baseline categorically by age, Boyarsky score, Qmax, and PSA level, determined by quartiles or tertiles. Taking into account the high number of patients at baseline (n ⫽ 1470), the distribution of the PVR volume was assumed to be normal. The Cochran-MantelHaenszel test was used to compare the ordinal categorical variables. The analysis of variance was used to compare the quantitative parameters. The analyses of the PVR volume changes with treatment were performed according to the intention to treat principle. To take into account the different durations of treatment between the studies, three endpoints were considered (1, 3, and 6 months). At each endpoint, the last PVR volume assessment during treatment was taken into account. The relationship between the individual changes in the PVR volume at the endpoint and the baseline PVR volume values was analyzed; in the case of a linear relationship, the regression lines and confidence intervals were provided per treatment group. Treatments were compared at each endpoint using a one-way analysis of covariance (treatment) with a fixed-effect model, taking as the covariate the PVR volume at D0 (the covariate was centered by subtracting the overall mean value at D0). No adjustment was performed.
RESULTS BASELINE CORRELATIONS A total of 1470 patients, 42 to 89 years old, underwent an assessment of their PVR volume at baseline. The clinical characteristics of these patients are provided in Table II. Of these 1470 patients, 722 (49%) and 283 (19%) had a baseline PVR volume of at least 100 mL and 150 mL, respectively. The relationship between the baseline PVR volume and the various clinical characteristics, classified by tertiles or quartiles, was assessed (Table III). It showed that the PVR volume was related to the baseline Qmax. A PVR volume of at least 100 mL was observed in 60%, 47%, and 39% of patients with a Qmax less than 8, 8 to 11, and greater than 11 mL, respectively (P ⫽ 0.001). A PVR volume of UROLOGY 57 (3), 2001
at least 150 mL was observed in 22%, 19%, and 15% of patients with a Qmax less than 8, 8 to 11, and greater than 11 mL/s, respectively (P ⫽ 0.005). The bladder capacity was also significantly related to the Qmax. A mean ⫾ SD value of 329 ⫾ 102 mL, 359 ⫾ 126 mL, and 381 ⫾ 136 mL was observed in patients with a Qmax less than 8, 8 to 11, and greater than 11 mL/s, respectively (P ⫽ 0.0001) (Fig. 1). Conversely, the PVR volume was not influenced by patient age, Boyarsky score, or PSA values. Similar results were observed with bladder capacity. ENDPOINT ANALYSIS Data on the changes in the PVR volume during treatment were complete and available for assessment in 912 of the patients (alfuzosin group, n ⫽ 584 and placebo group, n ⫽ 328). Whatever the endpoint (1, 3, or 6 months), the improvements in the PVR volume with alfuzosin were significantly greater than those observed with placebo (Fig. 2). At month 1, the mean decrease in the PVR volume was ⫺28.8 mL (⫺22%) and ⫺17.6 mL (⫺12%) with alfuzosin and placebo, respectively (P ⫽ 0.02). At month 3, the mean decrease in the PVR volume was ⫺35.5 mL (⫺27%) and ⫺22.5 mL (⫺17%) with alfuzosin and placebo, respectively (P ⫽ 0.01). At month 6, the mean decrease in the PVR volume was ⫺36.8 mL (⫺28%) and ⫺22.6 mL (⫺16%) with alfuzosin and placebo, respectively (P ⫽ 0.01). Expressed using a regression model, the decreases in the PVR volume at 1, 3, and 6 months with both alfuzosin and placebo were related to the baseline PVR volume and were particularly marked in those patients with a high PVR volume at baseline. However, whatever the baseline PVR volume, the changes were significantly more marked with alfuzosin than with placebo. At month 1, the regression coefficient r was ⫺0.64 for alfuzosin (n ⫽ 490) and ⫺0.43 for placebo (n ⫽ 319) (P ⬍0.025). At month 3, it was ⫺0.68 for alfuzosin (n ⫽ 582) and ⫺0.46 for placebo (n ⫽ 328) (P ⬍0.025). At month 6, it was ⫺0.73 for alfuzosin (n ⫽ 584) and ⫺0.50 for placebo (n ⫽ 328) (P ⬍0.025) (Fig. 3). Similar results were observed when the changes in the PVR volume were analyzed by category (50 mL or greater, 100 mL or greater, and 150 mL or greater) of PVR volume at baseline. Whatever the baseline PVR volume, the decreases in the PVR volume were significantly greater with alfuzosin than with placebo at 6 months (Fig. 4). The mean decrease in the PVR volume for those 912 patients with a PVR volume of 50 mL or greater at baseline was ⫺36.8 mL (⫺28%) and ⫺22.6 mL (⫺16%) with alfuzosin and placebo, respectively (P ⫽ 0.01). For the 427 patients with a PVR volume of 461
TABLE III. Relationship between baseline postvoid residual urine volume and age, Boyarsky score, maximum flow rate, and PSA levels Parameter Age (yr) ⬍60 ⱖ60 to ⬍65 ⱖ65 to ⬍70 ⱖ70 Baseline Boyarsky score ⬍8 ⱖ8 to ⬍11 ⱖ11 Baseline Qmax (mL/s) ⬍8 8–11 ⬎11 Baseline PSA (ng/mL) ⬍1.4 ⱖ1.4 to ⬍4 ⱖ4
Patients (n)
Baseline PVR Volume (mL) ⫾ ⫾ ⫾ ⫾
Patients with PVR >100 mL (%)
Patients with PVR >150 mL (%)
377 345 377 370
104 104 111 105
54 58 57 50
47 47 51 52
17 18 23 19
333 651 445
104 ⫾ 53 105 ⫾ 56 109 ⫾ 55
48 47 52
18 19 20
406 477 448
113 ⫾ 53 106 ⫾ 56 98 ⫾ 53
60* 47* 39*
22† 19† 15†
191 353 313
110 ⫾ 65 105 ⫾ 49 104 ⫾ 51
45 49 45
19 16 17
KEY: PSA ⫽ prostate-specific antigen; other abbreviations as in Table II. * P ⫽ 0.001 (Cochran-Mantel-Haenszel test on two categories: ⬍100 mL and ⱖ100 mL). † P ⫽ 0.005 (Cochran-Mantel-Haenszel test on two categories: ⬍150 mL and ⱖ150 mL).
FIGURE 1. Relationship between estimated bladder capacity and Qmax. Global P ⫽ 0.0001 (comparison using analysis of variance).
100 mL or greater at baseline, the mean decrease in the PVR volume was ⫺64.4 mL (⫺40%) and ⫺42.2 mL (⫺29%) with alfuzosin and placebo, respectively (P ⫽ 0.01). For the 155 patients with a PVR volume of 150 mL or greater at baseline, the mean decrease in the PVR volume was ⫺109.7 mL (⫺54%) and ⫺61.4 mL (⫺34%) with alfuzosin and placebo, respectively (P ⫽ 0.002). Comparable results were observed at months 1 and 3. Acute urinary retention occurred in 7 patients: 2 (0.3%) of 607 patients taking alfuzosin and 5 (1.4%) of 346 patients taking placebo. The mean age of these patients was 63 years (range 53 to 71), the mean Boyarsky score was 11 (range 6 to 20), and the mean Qmax was 8.8 mL/s (range 4.5 to 12). Six of these patients had a baseline PVR volume greater than 100 mL. 462
FIGURE 2. Changes in PVR volume with alfuzosin and placebo. Endpoint analysis at 1, 3, and 6 months. Data presented as the mean ⫾ standard error of the mean. *P ⫽ 0.02; **P ⫽ 0.01 (comparison using one-way analysis of covariance).
COMMENT This pooled analysis represents the largest study examining the relationship between the PVR volume and various clinical parameters in a population of patients with LUTS suggestive of BPH. The results suggest that, in a selected population representative of that enrolled in BPH clinical trials, the PVR volume is not related to age, LUTS, or PSA level, which was recently reported as a surrogate for prostate size.18 Conversely, the PVR volume was related to the Qmax. The percentage of patients with a PVR volume of at least 100 mL was significantly higher (60%) in patients most likely to be obstructed (Qmax less than 8 mL/s) compared with those patients with a Qmax greater than 11 mL/s (39%). This pooled analysis also showed UROLOGY 57 (3), 2001
FIGURE 4. Impact of baseline PVR volume analyzed by category (50 mL or greater, 100 mL or greater, and 150 mL or greater) on mean changes in PVR volume with alfuzosin and placebo (6-month endpoint analysis). Treatments compared using one-way (treatment) analysis of covariance.
FIGURE 3. Relationship between baseline PVR volume and changes in PVR volume with alfuzosin and placebo expressed using a regression model (6-month endpoint analysis). Linear regression lines with 95% confidence interval for alfuzosin (squares, n ⫽ 584) and placebo (circles, n ⫽ 328) are represented. Treatments compared using one-way (treatment) analysis of covariance.
that bladder capacity, approximatively calculated by the sum of the micturition volume (provided by the uroflowmeter) and the PVR volume (measured after uroflowmetry), was also significantly related to the Qmax, with patients with a Qmax less than 8 mL/s having a smaller bladder capacity (329 mL) than those with a Qmax greater than 11 mL/s (381 mL). This suggests that the presence of a significant PVR volume in patients with clinical BPH is associated with decreased bladder capacity. However, the impact of this decreased bladder capacity on LUTS, especially filling symptoms such as frequency, urgency, and nocturia, needs to be further characterized. Although some obstructed patients have a PVR volume less than 50 mL, it is considered that bladder outlet obstruction plays a role in the occurrence of PVR volume.19 Rosier et al.20 showed that 75% of elderly men with a PVR volume greater than 50 mL have bladder outlet obstruction; in addition, PVR volume was significantly higher and Qmax significantly lower in obstructed patients, as determined by pressure/flow analysis, compared with those who UROLOGY 57 (3), 2001
were not obstructed. Uroflowmetry is not a reliable method to assess obstruction, but the relationship between the Qmax and the PVR volume observed in our pooled analysis is not surprising and has already been reported by several investigators.21,22 The lack of a relationship between age and PVR volume observed in this pooled analysis is in agreement with data recently published by Kolman et al.8 in 477 randomly selected men, 40 to 79 years old. The odds of having a PVR volume greater than 50 mL were not significantly increased with age. However, these findings contrast with the results of another community-based study of 377 men, 55 to 74 years old, living in Rotterdam (The Netherlands), which demonstrated a significant increase with age in both the mean PVR volume and the percentage of men with a PVR volume value greater than 50 mL.23 In both the Olmsted County8 and the Rotterdam23 surveys, a modest but significant correlation was demonstrated between the PVR volume and prostate volume (as assessed by transrectal ultrasound). This relationship was not evident in our study, in which prostate volume was indirectly assessed by PSA levels, or in the BPH Treatment Outcomes Pilot Study.21 The lack of a consistent correlation between the PVR volume and prostate size may be related to the different methods of measurement, direct versus indirect. It may also be explained by the large intraindividual variability of PVR volume. Diurnal variations of the PVR volume that might reflect physiologic changes in sympathetic tone have been observed in elderly patients.23,24 However, the intraindividual variability of the PVR volume was not assessed in the present pooled analysis. Voiding in unfamiliar surroundings, which is often the case in clinical trials, may also lead to unrepresentative results.25 Finally, other factors such as the quality of detrusor contraction may also contribute to the occur463
rence of a PVR volume but were not assessed in the present study.20 The second objective of this study was to assess the effect on PVR volume of a clinically uroselective alpha1-blocker, alfuzosin, in comparison with placebo. Whatever the treatment group, the changes in the PVR volume increased with the amount of PVR volume at baseline, suggesting a regression to the mean effect. However, at all endpoints and whatever the baseline PVR volume value, the decreases in the PVR volume were significantly greater with alfuzosin than with placebo, demonstrating a real beneficial effect of alfuzosin on PVR volume. To our knowledge, only prazosin has been reported to cause a significant decrease in the PVR volume compared with placebo.26 That study was a double-blind, crossover study conducted in 20 patients with BPH and a Qmax less than 10 mL/s; the PVR volume was measured by catheterization. A decrease compared with the baseline in the PVR volume has been reported with other alpha1-blockers, but none has demonstrated a significant improvement compared with placebo.27–32 Hence, alfuzosin appears to be the only clinically uroselective alpha1-blocker that has been clearly demonstrated to have a positive impact on the PVR volume, as measured by transabdominal ultrasound, compared with placebo in a large number of patients with BPH. This beneficial effect of alfuzosin on PVR volume may be related to a direct relief of bladder outlet obstruction, as demonstrated by pressure-flow studies,10 by relaxing smooth muscle fibers located in the prostate, its capsule, and proximal urethra. Among those 953 patients randomly allocated to receive alfuzosin or placebo, only 2 (0.3%) of the 607 who received alfuzosin developed acute urinary retention compared with 5 (1.4%) of 346 who received placebo. This reduction in the incidence of acute urinary retention in the alfuzosin group within a 6-month follow-up period suggests a beneficial effect attributable to alfuzosin that requires additional assessment in a long-term study. It is interesting to note that 6 of the 7 patients who developed acute urinary retention had a baseline PVR volume greater than 100 mL. Clinical data collected from the residents of Olmsted County demonstrated that men with a PVR volume greater than 50 mL at baseline were about three times more likely to develop acute urinary retention during the 3 to 4 years of follow-up.8 Our pooled analysis also suggests that the PVR volume is a predictive factor of acute urinary retention. CONCLUSIONS In this population of patients with LUTS suggestive of BPH, the PVR volume and bladder capacity 464
were significantly related to the Qmax. Conversely, no relationship was evident with age, voided volume, LUTS, or prostate size (estimated using PSA levels). Alfuzosin, administered for 1 to 6 months, significantly decreased the PVR volume compared with placebo, and this effect was more pronounced in patients with a high PVR volume at baseline. The lower incidence of acute urinary retention observed with alfuzosin may be attributed to its positive impact on the PVR volume. REFERENCES 1. Koyanagi T, Artibani W, Correa R, et al: Initial diagnostic evaluation of men with lower urinary tract symptoms, in Denis L, Griffiths K, Khoury S, et al (Eds): Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), Paris, July 2–5, 1997. St Helier, Jersey, Health Publication, 1998, pp 181–264. 2. Elbadawi A: Voiding dysfunction in benign prostatic hyperplasia: trends, controversies and recent revelations. Urology 51(suppl 5A): 62– 82, 1998. 3. Abrams P, Buzelin JM, and Griffiths D: The urodynamic assessment of lower urinary tract symptoms, in Denis L, Griffiths K, Khoury S, et al (Eds): Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), Paris, July 2–5, 1997. St Helier, Jersey, Health Publication, 1998, pp 323–377. 4. Dunsmuir WD, Feneley M, Corry DA, et al: The day-today variation (test-retest reliability) of residual urine measurement. Br J Urol 77: 192–193, 1996. 5. Wasson JH, Reda DJ, Bruskewitz RC, et al: A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. N Engl J Med 332: 75–79, 1995. 6. Gower PE, and Roberts AP: Upper urinary tract infection, aspects and mechanisms, in Franc¸ois B, and Perrin P (Eds): Urinary Infection: Insights and Prospects. Oxford, Butterworth-Heinemann, 1983, pp 57–71. 7. Streem SB: Bladder calculi, in Rous SN (Ed): Stone Disease: Diagnosis and Management. San Francisco, Grune & Stratton, 1987, pp 335–345. 8. Kolman C, Girman CJ, Jacobsen SJ, et al: Distribution of post-void residual urine in randomly selected men. J Urol 161: 122–127, 1999. 9. Jardin A, Bensadoun H, Delauche-Cavallier MC, et al: Alfuzosin for treatment of benign prostatic hypertrophy. Lancet 337: 1457–1461, 1991. 10. Martorana G, Giberti C, Di Silvero F, et al: Effects of short-term treatment with ␣1-blocker alfuzosin on urodynamic pressure/flow parameters in patients with benign prostatic hyperplasia. Eur Urol 32: 47–53, 1997. 11. Stephenson TP, Jensen RD, and the PRANALF Group: A placebo-controlled study of the efficacy and tolerability of alfuzosin and prazosin, for the treatment of benign prostatic hypertrophy (BPH), in Hald T, Alken P, and Boccon-Gibod L (Eds): Proceedings of the 11th Congress of the European Association of Urology, Berlin, Germany. Basel, Switzerland, Karger, 1994, p 25. 12. Buzelin JM, Hebert M, Blondin P, and the PRAZALF Group: Alpha-blocking treatment with alfuzosin in symptomatic benign prostatic hyperplasia: comparative study with prazosin. Br J Urol 72: 922–927, 1993. 13. Abbou CC, Hozneck A, McCarthy C, and the XATTAD Study Group: Alfuzosin, an uroselective ␣1 blocker versus Pygeum africanum, a plant extract: a randomized controlled trial in patients with symptomatic benign hypertrophy (BPH). Eur Urol 30(suppl 2): 77, 1996. UROLOGY 57 (3), 2001
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POSTVOID RESIDUAL URINE IN PATIENTS WITH LOWER URINARY TRACT SYMPTOMS SUGGESTIVE OF BENIGN PROSTATIC HYPERPLASIA: POOLED ANALYSIS OF ELEVEN CONTROLLED STUDIES WITH ALFUZOSIN S. ALAN MCNEILL, TIMOTHY B. HARGREAVE, CHRISTINE GEFFRIAUD-RICOUARD, JEAN-PHILIPPE SANTONI, AND CLAUS G. ROEHRBORN
ABSTRACT Objectives. A pooled analysis was conducted in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia to examine the relationship between the postvoid residual urine (PVR) volume and various clinical characteristics and to assess the effect of alfuzosin, a clinically uroselective alpha1blocker, on PVR volume and any other associated outcome. Methods. Nine hundred fifty-three patients, 42 to 89 years old, with a baseline PVR volume between 50 and 350 mL (mean 106 mL) were enrolled in 11 double-blind controlled studies and received either alfuzosin (n ⫽ 607) or placebo (n ⫽ 346) for 1 to 6 months. The relationships between the baseline PVR volume measured by transabdominal ultrasound and age, symptoms, maximum flow rate (Qmax), estimated bladder capacity, and prostate-specific antigen level were assessed. The changes in the PVR volume with treatment were evaluated in all available patients at three endpoints (1, 3, and 6 months). Results. At baseline, a PVR volume of 100 mL or greater was observed in 60%, 47%, and 39% of patients with a Qmax less than 8, 8 to 11, and greater than 11 mL/s, respectively (P ⫽ 0.001). The bladder capacity was also significantly related to the Qmax (P ⫽ 0.0001). No relationship was found between PVR volume and age, symptoms, or prostate-specific antigen level. The changes in the PVR volume with treatment were related to the baseline PVR volume. However, at all endpoints and whatever the baseline PVR volume, the decreases in the PVR volume were significantly (P ⬍0.01) greater with alfuzosin than with placebo. Acute urinary retention occurred in 7 patients (2 [0.3%] of 607 patients taking alfuzosin and 5 [1.4%] of 346 patients taking placebo); 6 of these 7 patients had a baseline PVR volume greater than 100 mL. Conclusions. In this population of men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, the PVR volume and bladder capacity were related to the baseline Qmax. Alfuzosin significantly reduced the PVR volume compared with placebo, and this effect was more marked in patients with a high PVR volume at baseline. Acute urinary retention occurred mainly in patients with a PVR volume greater than 100 mL and was less frequent in patients taking alfuzosin than in those taking placebo. UROLOGY 57: 459–465, 2001. © 2001, Elsevier Science Inc.
M
easurement of the postvoid residual urine (PVR) volume using transabdominal ultrasound is recommended by the International Consultation on Benign Prostatic Hyperplasia (BPH) at
the initial assessment and at follow-up examinations of patients under watchful waiting or other conservative treatment regimens.1 The presence of a PVR volume in patients with BPH is commonly
There was no direct funding for this meta-analysis, but each included study was funded by Sanofi-Synthe´labo. S. A. McNeill, C. G. Roehrborn, and T. B. Hargreave are funded clinical investigators for Sanofi-Synthe´labo. From the Western General Hospital, Edinburgh, Scotland, United Kingdom; Sanofi-Synthe´labo, Paris, France; and University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
Reprint requests: S. Alan McNeill, M.D., Department of Urology, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, Scotland Submitted: July 26, 2000, accepted (with revisions): October 16, 2000
© 2001, ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED
0090-4295/01/$20.00 PII S0090-4295(00)01021-9 459
TABLE I. Description of randomized studies included in the pooled analysis
Study BPH-ALF9 MCE2 UDM1 ALFURO10 PRANALF11 PRAZALF12 XATTAD13 PERMALF14 DALBI15 ALGEBI16 ALFIN17 Total
Design Placebo-controlled Placebo-controlled Placebo-controlled Placebo-controlled Placebo-controlled vs. other drug Controlled vs. other drug Controlled vs. other drug Controlled vs. other drug Placebo-controlled Placebo-controlled Controlled vs. other drug
Main Inclusion Criteria Boyarsky Boyarsky Boyarsky Boyarsky Boyarsky
ⱖ6 ⱖ6 ⱖ6, Qmax 5–12 mL/s ⱖ6, Qmax 5–12 mL/s ⱖ9, Qmax ⱕ15 mL/s
Frequency, Qmax ⬍15 mL/s Frequency, Qmax 5–15 mL/s Frequency, Qmax ⬍15 mL/s Frequency, Qmax 5–12 mL/s Frequency, Qmax 5–15 mL/s IPSS ⬎7, Qmax 5–15 mL/s
Randomized Treatment Patients at Patients (n) Duration Baseline Alfuzosin Placebo (mo) (n) 160 48 40 25 73
74 21 18 10 24
86 27 22 15 24
61 172 20 118 215 538 1470
28 83 9 58 103 179 607
— — — 60 112 — 346
6 6 3 1 1 1 2* 1 1 3 6
KEY: Qmax ⫽ maximum urinary flow rate; IPSS ⫽ International Prostate Symptom Score. * For XATTAD study, the endpoint was considered at month 3 instead of month 2, which was the actual treatment duration.
associated with urodynamically proved bladder outlet obstruction. However, the usefulness of the PVR volume determination as a diagnostic test is still questioned, because no clear relationship has been found between the PVR volume and either the severity or the duration of outlet obstruction.2 In addition, the absence of a PVR volume does not rule out severe obstruction.3 This may in part be related to the large interindividual and intraindividual variability of this parameter, especially in those patients with a large PVR volume.4 Nevertheless, the presence of a large PVR volume remains a common indication for transurethral resection of the prostate.5 It may also predispose patients to the occurrence of serious BPH complications such as urinary tract infection,6 bladder calculi,7 and upper tract dilation with renal function impairment (especially in case of high detrusor pressure).3 In addition, clinical data collected from randomly selected men, 40 to 79 years old (all residents of Olmsted Country, Minn), suggest that men with a PVR volume greater than 50 mL are about three times more likely to develop acute urinary retention.8 We sought to determine the relationship between PVR and various clinical parameters such as age, lower urinary tract symptoms (LUTS), maximum flow rate (Qmax), estimated bladder capacity, and prostate-specific antigen (PSA) and to characterize the effect of alfuzosin, a clinically uroselective alpha1-blocker, on the PVR volume and any associated impact on outcome in a pooled analysis of 11 double-blind controlled studies of patients with LUTS suggestive of BPH. 460
MATERIAL AND METHODS The clinical data of 1470 patients with LUTS suggestive of BPH and a PVR volume between 50 and 350 mL at the time of study inclusion were pooled. These patients were enrolled in 11 European double-blind controlled studies with alfuzosin, which have been published as full reports or abstracts.9 –17 The design, entry criteria, and number of patients available for evaluation per visit for each trial are shown in Table I. Of these 1470 patients, 953 were randomly allocated to receive either alfuzosin (immediate-release formulation, 2.5 mg three times daily, n ⫽ 267; sustained-release formulation, 5 mg twice daily, n ⫽ 340; total n ⫽ 607) or placebo (n ⫽ 346) for 1 to 6 months, and 912 patients (alfuzosin group, n ⫽ 584; placebo group, n ⫽ 328) underwent an assessment of PVR volume after the baseline assessment. Both alfuzosin formulations were bioequivalent; a higher dosage was required for the twice daily formulation because of a loss of bioavailability of about 20% compared with the three times daily formulation. The remaining patients (n ⫽ 517) received various other agents (eg, Serenoa repens, Pygeum africanum, prazosin, or finasteride alone or in combination with alfuzosin). The baseline correlations between the PVR volume and various clinical parameters (age, LUTS, Qmax, estimated bladder capacity, and PSA) were assessed in the overall population (n ⫽ 1470). The analysis of the PVR volume changes with treatment was limited to the alfuzosin and placebo groups that were the most representative in terms of the number of patients. The PVR volume was determined by transabdominal ultrasound measurement performed immediately after the uroflowmetry recording. No particular formula was specified by the protocol, but investigators were requested to use the same formula for each patient. The bladder capacity was indirectly estimated by the sum of the voided volume (provided by the uroflowmeter) and the PVR volume measurement. LUTS were assessed in all studies using a modified Boyarsky score,9 which included seven items scored 0 to 3 in increasing order of severity (maximum theoretical score of 21). In the two most recent studies,16,17 LUTS were also assessed using the International Prostate Symptom Score questionnaire. All uroflowmetry curves were reviewed and validated by an expert unaware of the treatment assignment. A voided volume of at least 100 mL was required to consider a curve valid. PSA values UROLOGY 57 (3), 2001
TABLE II. Clinical characteristics of patients at study inclusion Overall Population (n ⴝ 1470)
Characteristic Age (yr) Symptom duration (mo) Boyarsky total score Qmax (mL/s) PVR volume (mL) No. of patients (%) with baseline PVR volume of 50–100 mL 100–150 mL ⱖ150 mL
64.5 39.5 9.5 9.8 106.1
⫾ ⫾ ⫾ ⫾ ⫾
7.4 (42–89) 34.0 (1–240) 2.6 (2–20) 4.0 (2–46) 54.5 (50–350)
748 (51) 439 (30) 283 (19)
KEY: Qmax ⫽ maximum urinary flow rate; PVR ⫽ postvoid residual (urine). Data presented as the mean ⫾ SD, with the range in parentheses, unless otherwise noted.
were measured at baseline in the three most recent studies.15–17
STATISTICAL ANALYSIS The PVR volume was described at baseline categorically by age, Boyarsky score, Qmax, and PSA level, determined by quartiles or tertiles. Taking into account the high number of patients at baseline (n ⫽ 1470), the distribution of the PVR volume was assumed to be normal. The Cochran-MantelHaenszel test was used to compare the ordinal categorical variables. The analysis of variance was used to compare the quantitative parameters. The analyses of the PVR volume changes with treatment were performed according to the intention to treat principle. To take into account the different durations of treatment between the studies, three endpoints were considered (1, 3, and 6 months). At each endpoint, the last PVR volume assessment during treatment was taken into account. The relationship between the individual changes in the PVR volume at the endpoint and the baseline PVR volume values was analyzed; in the case of a linear relationship, the regression lines and confidence intervals were provided per treatment group. Treatments were compared at each endpoint using a one-way analysis of covariance (treatment) with a fixed-effect model, taking as the covariate the PVR volume at D0 (the covariate was centered by subtracting the overall mean value at D0). No adjustment was performed.
RESULTS BASELINE CORRELATIONS A total of 1470 patients, 42 to 89 years old, underwent an assessment of their PVR volume at baseline. The clinical characteristics of these patients are provided in Table II. Of these 1470 patients, 722 (49%) and 283 (19%) had a baseline PVR volume of at least 100 mL and 150 mL, respectively. The relationship between the baseline PVR volume and the various clinical characteristics, classified by tertiles or quartiles, was assessed (Table III). It showed that the PVR volume was related to the baseline Qmax. A PVR volume of at least 100 mL was observed in 60%, 47%, and 39% of patients with a Qmax less than 8, 8 to 11, and greater than 11 mL, respectively (P ⫽ 0.001). A PVR volume of UROLOGY 57 (3), 2001
at least 150 mL was observed in 22%, 19%, and 15% of patients with a Qmax less than 8, 8 to 11, and greater than 11 mL/s, respectively (P ⫽ 0.005). The bladder capacity was also significantly related to the Qmax. A mean ⫾ SD value of 329 ⫾ 102 mL, 359 ⫾ 126 mL, and 381 ⫾ 136 mL was observed in patients with a Qmax less than 8, 8 to 11, and greater than 11 mL/s, respectively (P ⫽ 0.0001) (Fig. 1). Conversely, the PVR volume was not influenced by patient age, Boyarsky score, or PSA values. Similar results were observed with bladder capacity. ENDPOINT ANALYSIS Data on the changes in the PVR volume during treatment were complete and available for assessment in 912 of the patients (alfuzosin group, n ⫽ 584 and placebo group, n ⫽ 328). Whatever the endpoint (1, 3, or 6 months), the improvements in the PVR volume with alfuzosin were significantly greater than those observed with placebo (Fig. 2). At month 1, the mean decrease in the PVR volume was ⫺28.8 mL (⫺22%) and ⫺17.6 mL (⫺12%) with alfuzosin and placebo, respectively (P ⫽ 0.02). At month 3, the mean decrease in the PVR volume was ⫺35.5 mL (⫺27%) and ⫺22.5 mL (⫺17%) with alfuzosin and placebo, respectively (P ⫽ 0.01). At month 6, the mean decrease in the PVR volume was ⫺36.8 mL (⫺28%) and ⫺22.6 mL (⫺16%) with alfuzosin and placebo, respectively (P ⫽ 0.01). Expressed using a regression model, the decreases in the PVR volume at 1, 3, and 6 months with both alfuzosin and placebo were related to the baseline PVR volume and were particularly marked in those patients with a high PVR volume at baseline. However, whatever the baseline PVR volume, the changes were significantly more marked with alfuzosin than with placebo. At month 1, the regression coefficient r was ⫺0.64 for alfuzosin (n ⫽ 490) and ⫺0.43 for placebo (n ⫽ 319) (P ⬍0.025). At month 3, it was ⫺0.68 for alfuzosin (n ⫽ 582) and ⫺0.46 for placebo (n ⫽ 328) (P ⬍0.025). At month 6, it was ⫺0.73 for alfuzosin (n ⫽ 584) and ⫺0.50 for placebo (n ⫽ 328) (P ⬍0.025) (Fig. 3). Similar results were observed when the changes in the PVR volume were analyzed by category (50 mL or greater, 100 mL or greater, and 150 mL or greater) of PVR volume at baseline. Whatever the baseline PVR volume, the decreases in the PVR volume were significantly greater with alfuzosin than with placebo at 6 months (Fig. 4). The mean decrease in the PVR volume for those 912 patients with a PVR volume of 50 mL or greater at baseline was ⫺36.8 mL (⫺28%) and ⫺22.6 mL (⫺16%) with alfuzosin and placebo, respectively (P ⫽ 0.01). For the 427 patients with a PVR volume of 461
TABLE III. Relationship between baseline postvoid residual urine volume and age, Boyarsky score, maximum flow rate, and PSA levels Parameter Age (yr) ⬍60 ⱖ60 to ⬍65 ⱖ65 to ⬍70 ⱖ70 Baseline Boyarsky score ⬍8 ⱖ8 to ⬍11 ⱖ11 Baseline Qmax (mL/s) ⬍8 8–11 ⬎11 Baseline PSA (ng/mL) ⬍1.4 ⱖ1.4 to ⬍4 ⱖ4
Patients (n)
Baseline PVR Volume (mL) ⫾ ⫾ ⫾ ⫾
Patients with PVR >100 mL (%)
Patients with PVR >150 mL (%)
377 345 377 370
104 104 111 105
54 58 57 50
47 47 51 52
17 18 23 19
333 651 445
104 ⫾ 53 105 ⫾ 56 109 ⫾ 55
48 47 52
18 19 20
406 477 448
113 ⫾ 53 106 ⫾ 56 98 ⫾ 53
60* 47* 39*
22† 19† 15†
191 353 313
110 ⫾ 65 105 ⫾ 49 104 ⫾ 51
45 49 45
19 16 17
KEY: PSA ⫽ prostate-specific antigen; other abbreviations as in Table II. * P ⫽ 0.001 (Cochran-Mantel-Haenszel test on two categories: ⬍100 mL and ⱖ100 mL). † P ⫽ 0.005 (Cochran-Mantel-Haenszel test on two categories: ⬍150 mL and ⱖ150 mL).
FIGURE 1. Relationship between estimated bladder capacity and Qmax. Global P ⫽ 0.0001 (comparison using analysis of variance).
100 mL or greater at baseline, the mean decrease in the PVR volume was ⫺64.4 mL (⫺40%) and ⫺42.2 mL (⫺29%) with alfuzosin and placebo, respectively (P ⫽ 0.01). For the 155 patients with a PVR volume of 150 mL or greater at baseline, the mean decrease in the PVR volume was ⫺109.7 mL (⫺54%) and ⫺61.4 mL (⫺34%) with alfuzosin and placebo, respectively (P ⫽ 0.002). Comparable results were observed at months 1 and 3. Acute urinary retention occurred in 7 patients: 2 (0.3%) of 607 patients taking alfuzosin and 5 (1.4%) of 346 patients taking placebo. The mean age of these patients was 63 years (range 53 to 71), the mean Boyarsky score was 11 (range 6 to 20), and the mean Qmax was 8.8 mL/s (range 4.5 to 12). Six of these patients had a baseline PVR volume greater than 100 mL. 462
FIGURE 2. Changes in PVR volume with alfuzosin and placebo. Endpoint analysis at 1, 3, and 6 months. Data presented as the mean ⫾ standard error of the mean. *P ⫽ 0.02; **P ⫽ 0.01 (comparison using one-way analysis of covariance).
COMMENT This pooled analysis represents the largest study examining the relationship between the PVR volume and various clinical parameters in a population of patients with LUTS suggestive of BPH. The results suggest that, in a selected population representative of that enrolled in BPH clinical trials, the PVR volume is not related to age, LUTS, or PSA level, which was recently reported as a surrogate for prostate size.18 Conversely, the PVR volume was related to the Qmax. The percentage of patients with a PVR volume of at least 100 mL was significantly higher (60%) in patients most likely to be obstructed (Qmax less than 8 mL/s) compared with those patients with a Qmax greater than 11 mL/s (39%). This pooled analysis also showed UROLOGY 57 (3), 2001
FIGURE 4. Impact of baseline PVR volume analyzed by category (50 mL or greater, 100 mL or greater, and 150 mL or greater) on mean changes in PVR volume with alfuzosin and placebo (6-month endpoint analysis). Treatments compared using one-way (treatment) analysis of covariance.
FIGURE 3. Relationship between baseline PVR volume and changes in PVR volume with alfuzosin and placebo expressed using a regression model (6-month endpoint analysis). Linear regression lines with 95% confidence interval for alfuzosin (squares, n ⫽ 584) and placebo (circles, n ⫽ 328) are represented. Treatments compared using one-way (treatment) analysis of covariance.
that bladder capacity, approximatively calculated by the sum of the micturition volume (provided by the uroflowmeter) and the PVR volume (measured after uroflowmetry), was also significantly related to the Qmax, with patients with a Qmax less than 8 mL/s having a smaller bladder capacity (329 mL) than those with a Qmax greater than 11 mL/s (381 mL). This suggests that the presence of a significant PVR volume in patients with clinical BPH is associated with decreased bladder capacity. However, the impact of this decreased bladder capacity on LUTS, especially filling symptoms such as frequency, urgency, and nocturia, needs to be further characterized. Although some obstructed patients have a PVR volume less than 50 mL, it is considered that bladder outlet obstruction plays a role in the occurrence of PVR volume.19 Rosier et al.20 showed that 75% of elderly men with a PVR volume greater than 50 mL have bladder outlet obstruction; in addition, PVR volume was significantly higher and Qmax significantly lower in obstructed patients, as determined by pressure/flow analysis, compared with those who UROLOGY 57 (3), 2001
were not obstructed. Uroflowmetry is not a reliable method to assess obstruction, but the relationship between the Qmax and the PVR volume observed in our pooled analysis is not surprising and has already been reported by several investigators.21,22 The lack of a relationship between age and PVR volume observed in this pooled analysis is in agreement with data recently published by Kolman et al.8 in 477 randomly selected men, 40 to 79 years old. The odds of having a PVR volume greater than 50 mL were not significantly increased with age. However, these findings contrast with the results of another community-based study of 377 men, 55 to 74 years old, living in Rotterdam (The Netherlands), which demonstrated a significant increase with age in both the mean PVR volume and the percentage of men with a PVR volume value greater than 50 mL.23 In both the Olmsted County8 and the Rotterdam23 surveys, a modest but significant correlation was demonstrated between the PVR volume and prostate volume (as assessed by transrectal ultrasound). This relationship was not evident in our study, in which prostate volume was indirectly assessed by PSA levels, or in the BPH Treatment Outcomes Pilot Study.21 The lack of a consistent correlation between the PVR volume and prostate size may be related to the different methods of measurement, direct versus indirect. It may also be explained by the large intraindividual variability of PVR volume. Diurnal variations of the PVR volume that might reflect physiologic changes in sympathetic tone have been observed in elderly patients.23,24 However, the intraindividual variability of the PVR volume was not assessed in the present pooled analysis. Voiding in unfamiliar surroundings, which is often the case in clinical trials, may also lead to unrepresentative results.25 Finally, other factors such as the quality of detrusor contraction may also contribute to the occur463
rence of a PVR volume but were not assessed in the present study.20 The second objective of this study was to assess the effect on PVR volume of a clinically uroselective alpha1-blocker, alfuzosin, in comparison with placebo. Whatever the treatment group, the changes in the PVR volume increased with the amount of PVR volume at baseline, suggesting a regression to the mean effect. However, at all endpoints and whatever the baseline PVR volume value, the decreases in the PVR volume were significantly greater with alfuzosin than with placebo, demonstrating a real beneficial effect of alfuzosin on PVR volume. To our knowledge, only prazosin has been reported to cause a significant decrease in the PVR volume compared with placebo.26 That study was a double-blind, crossover study conducted in 20 patients with BPH and a Qmax less than 10 mL/s; the PVR volume was measured by catheterization. A decrease compared with the baseline in the PVR volume has been reported with other alpha1-blockers, but none has demonstrated a significant improvement compared with placebo.27–32 Hence, alfuzosin appears to be the only clinically uroselective alpha1-blocker that has been clearly demonstrated to have a positive impact on the PVR volume, as measured by transabdominal ultrasound, compared with placebo in a large number of patients with BPH. This beneficial effect of alfuzosin on PVR volume may be related to a direct relief of bladder outlet obstruction, as demonstrated by pressure-flow studies,10 by relaxing smooth muscle fibers located in the prostate, its capsule, and proximal urethra. Among those 953 patients randomly allocated to receive alfuzosin or placebo, only 2 (0.3%) of the 607 who received alfuzosin developed acute urinary retention compared with 5 (1.4%) of 346 who received placebo. This reduction in the incidence of acute urinary retention in the alfuzosin group within a 6-month follow-up period suggests a beneficial effect attributable to alfuzosin that requires additional assessment in a long-term study. It is interesting to note that 6 of the 7 patients who developed acute urinary retention had a baseline PVR volume greater than 100 mL. Clinical data collected from the residents of Olmsted County demonstrated that men with a PVR volume greater than 50 mL at baseline were about three times more likely to develop acute urinary retention during the 3 to 4 years of follow-up.8 Our pooled analysis also suggests that the PVR volume is a predictive factor of acute urinary retention. CONCLUSIONS In this population of patients with LUTS suggestive of BPH, the PVR volume and bladder capacity 464
were significantly related to the Qmax. Conversely, no relationship was evident with age, voided volume, LUTS, or prostate size (estimated using PSA levels). Alfuzosin, administered for 1 to 6 months, significantly decreased the PVR volume compared with placebo, and this effect was more pronounced in patients with a high PVR volume at baseline. The lower incidence of acute urinary retention observed with alfuzosin may be attributed to its positive impact on the PVR volume. REFERENCES 1. Koyanagi T, Artibani W, Correa R, et al: Initial diagnostic evaluation of men with lower urinary tract symptoms, in Denis L, Griffiths K, Khoury S, et al (Eds): Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), Paris, July 2–5, 1997. St Helier, Jersey, Health Publication, 1998, pp 181–264. 2. Elbadawi A: Voiding dysfunction in benign prostatic hyperplasia: trends, controversies and recent revelations. Urology 51(suppl 5A): 62– 82, 1998. 3. Abrams P, Buzelin JM, and Griffiths D: The urodynamic assessment of lower urinary tract symptoms, in Denis L, Griffiths K, Khoury S, et al (Eds): Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), Paris, July 2–5, 1997. St Helier, Jersey, Health Publication, 1998, pp 323–377. 4. Dunsmuir WD, Feneley M, Corry DA, et al: The day-today variation (test-retest reliability) of residual urine measurement. Br J Urol 77: 192–193, 1996. 5. Wasson JH, Reda DJ, Bruskewitz RC, et al: A comparison of transurethral surgery with watchful waiting for moderate symptoms of benign prostatic hyperplasia. N Engl J Med 332: 75–79, 1995. 6. Gower PE, and Roberts AP: Upper urinary tract infection, aspects and mechanisms, in Franc¸ois B, and Perrin P (Eds): Urinary Infection: Insights and Prospects. Oxford, Butterworth-Heinemann, 1983, pp 57–71. 7. Streem SB: Bladder calculi, in Rous SN (Ed): Stone Disease: Diagnosis and Management. San Francisco, Grune & Stratton, 1987, pp 335–345. 8. Kolman C, Girman CJ, Jacobsen SJ, et al: Distribution of post-void residual urine in randomly selected men. J Urol 161: 122–127, 1999. 9. Jardin A, Bensadoun H, Delauche-Cavallier MC, et al: Alfuzosin for treatment of benign prostatic hypertrophy. Lancet 337: 1457–1461, 1991. 10. Martorana G, Giberti C, Di Silvero F, et al: Effects of short-term treatment with ␣1-blocker alfuzosin on urodynamic pressure/flow parameters in patients with benign prostatic hyperplasia. Eur Urol 32: 47–53, 1997. 11. Stephenson TP, Jensen RD, and the PRANALF Group: A placebo-controlled study of the efficacy and tolerability of alfuzosin and prazosin, for the treatment of benign prostatic hypertrophy (BPH), in Hald T, Alken P, and Boccon-Gibod L (Eds): Proceedings of the 11th Congress of the European Association of Urology, Berlin, Germany. Basel, Switzerland, Karger, 1994, p 25. 12. Buzelin JM, Hebert M, Blondin P, and the PRAZALF Group: Alpha-blocking treatment with alfuzosin in symptomatic benign prostatic hyperplasia: comparative study with prazosin. Br J Urol 72: 922–927, 1993. 13. Abbou CC, Hozneck A, McCarthy C, and the XATTAD Study Group: Alfuzosin, an uroselective ␣1 blocker versus Pygeum africanum, a plant extract: a randomized controlled trial in patients with symptomatic benign hypertrophy (BPH). Eur Urol 30(suppl 2): 77, 1996. UROLOGY 57 (3), 2001
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