Impact of tamsulosin on urinary retention following early catheter removal after robot-assisted laparoscopic radical prostatectomy: A prospective randomized controlled trial

Authors


  • The trial results were presented at the 30th WCE held in Istanbul, Turkey in September 2012.

Abstract

Objectives

To examine the impact of tamsulosin on the rate of acute urinary retention following early catheter removal after robot-assisted laparoscopic radical prostatectomy.

Methods

A total of 236 patients who underwent robot-assisted laparoscopic radical prostatectomy for prostate cancer carried out by a single surgeon were enrolled in this randomized study. Patients were randomly divided into two groups: treatment with tamsulosin (0.4 mg) from 1 day before to 14 days after surgery (tamsulosin group), or no tamsulosin treatment (control group). The urethral catheter was removed on the fifth postoperative day. The primary end-point was the acute urinary retention rate. Changes in each domain of the International Continence Society male short-form questionnaire and uroflowmetry parameters were secondary end-points.

Results

The primary end-point was assessed in 218 patients (92.4%; n = 109 in each group). It was not assessed in 18 patients because of cystographic leak from the vesicourethral anastomosis. The acute urinary retention rate was lower in the tamsulosin group (7.3%) than in the control group (17.4%, P = 0.018). Multivariate logistic regression analysis identified tamsulosin treatment and the operative experience of the surgeon as independent risk factors for acute urinary retention. Tamsulosin-treated patients had a 0.30-fold lower risk of developing acute urinary retention compared with control patients (95% confidence interval 0.12–0.76; P = 0.011). None of the International Continence Society male questionnaire domain scores showed significant changes between the groups.

Conclusions

Perioperative treatment with tamsulosin in patients undergoing robot-assisted laparoscopic radical prostatectomy reduces the rate of acute urinary retention after early catheter removal, without aggravating urinary incontinence.

Abbreviations & Acronyms
AUR

acute urinary retention

ICS

International Continence Society

IPSS

International Prostate Symptom Score

PSA

prostate-specific antigen

PVR

postvoid residual volume

Qmax

maximum urinary flow rate

QOL

quality of life

RARP

robot-assisted laparoscopic radical prostatectomy

RP

radical prostatectomy

SD

standard deviation

SF

short form

Introduction

Although prolonged urethral catheterization is necessary because of its perceived advantages in preventing urinary leak and urinoma, minimizing scar formation, and potentially improving continence, it is a major source of discomfort and irritation during the early weeks after RP for prostate cancer.[1, 2] Evidence suggests that early catheter removal after open or laparoscopic RP could lead to urinary retention caused by persistent anastomotic edema or by hematuria with clot formation.[3-5]

RARP allows very precise urethrovesical anastomosis by filtering hand tremors, and providing magnification and scaling for the surgical movements. Theoretically, the duration of catheterization might be shorter with RARP than with open or laparoscopic RP; however, catheterization for at least 7 days after RARP has been reported in the literature, even at centers carrying out a high number of RARP procedures.[6, 7]

To avoid the use of a urethral catheter without compromising the outcome in the initial few days after RARP, several techniques (such as a custom-designed suprapubic device) have been proposed, with promising results.[8-10] Nevertheless, most centers carrying out RARP use the conventional urethral catheter, because of a lack of availability of alternative devices or a lack of long-term follow up.

To date, few studies have addressed the efficacy of alpha-blockers in patients receiving RP for prostate cancer. The efficacy of tamsulosin in reducing the incidence of urinary retention after early catheter removal was evaluated after open RP in a non-randomized study that compared two sequential groups of patients.[11] Naftopidil also improves lower urinary tract symptoms in patients after RP.[12] Given the increasing use of RARP worldwide, any method that can reduce patient discomfort without compromising the surgical outcome would be useful.[13] Therefore, the purpose of the present randomized controlled trial was to examine the impact of tamsulosin on the rate of AUR following early catheter removal after RARP.

Methods

Enrolment

Participants received detailed information about the study procedure and provided written informed consent before enrolling in the present prospective, randomized controlled study. The study was approved by the local institutional review board and registered at the ClinicalTrial.gov website (ID: NCT 01209988). Patients admitted for a planned RARP to treat clinically localized prostate cancer between April 2010 and July 2011 were eligible for inclusion. Although the economic considerations are vital, the adopted surgical method (open vs robot-assisted) was decided by joint consensus between the patient and surgeon, and all included patients were theoretically suitable for either approach. Patients were enrolled in the study at the time of histological diagnosis of prostate cancer and randomly divided into two groups: treatment with 0.4 mg of tamsulosin from the day before RARP up until 14 days after surgery (tamsulosin group), or no tamsulosin treatment (control group). If a patient was taking alpha-blockers, the medications were discontinued after enrolment in the study.

Preoperative clinical evaluation consisted of a medical history, as well as neurological and physical examinations. Prostate volume was measured by magnetic resonance imaging using a 3T magnetic resonance system (Achieva 3.0T TX; Philips Healthcare, Best, the Netherlands). The ICS male short-form questionnaire and IPSS questionnaire were completed before surgery.

The primary end-point of the present study was the rate of AUR. Secondary end-points included changes in each domain of the ICS male short-form and IPSS questionnaires, and uroflowmetry parameters.

Surgical technique

All RARP procedures were carried out by a single surgeon (CSK) under general anesthesia. Before the initiation of the present study, the surgeon had logged 467 open RP procedures since January 2000, and 141 RARP procedures between August 2007 and March 2010. During the study period, in addition to the 236 RP procedures carried out as part of the present study, an additional 115 open RP procedures were carried out simultaneously.

All of the patients underwent a transperitoneal technique with early exposure of the prostatovesical junction. Nerve sparing was carried out athermally for all preoperatively potent patients on sides not suspicious for cancer extension. Bilateral pelvic lymph node dissection was carried out for sampling purposes in all patients. A posterior reconstruction of the rhabdosphincter was carried out before vesicourethral anastomosis, as described by Rocco et al.[14] The anastomosis was carried out using a continuous running suture with two 3-0 monocryl sutures tied together. Periurethral suspension stitching or bladder neck plication was not used during RARP. A 20-Fr Foley catheter was inserted after urethrovesical anastomosis. Cystograms were obtained routinely on postoperative day 5. The urethral catheter was immediately removed in patients without evidence of anastomotic leakage. Cox-2 inhibitors were routinely administered postoperatively to all patients.

Measurements

The primary outcome measure was the development of AUR immediately after urethral catheter removal on postoperative day 5. Acute urinary retention was defined as a painful, palpable or percussable bladder, with the patient unable to pass any urine.[15] Secondary outcome measures were assessed by the validated symptom scores (IPSS and ICS male short-form questionnaires) at baseline and 2 weeks after urethral catheter removal. Changes in uroflowmetric parameters (maximum urinary flow rate and post-void residual volume) were also evaluated.

Sample size

The sample size was calculated based on the results of a pilot study. Although the difference in the AUR rate between the tamsulosin and control group was 7.4% in a previously published open series, the estimated difference in the AUR rate was approximately 15% in the pilot RARP study.[11] Using a two-sided test with a type one error rate of 0.05, the present study had 90% power to detect a 15% relative difference between the two groups in terms of the proportion of patients that developed AUR after early catheter removal, assuming a total sample size of 106 patients. To accommodate for an estimated 10% dropout rate, 118 patients were included in each group.

Statistical methods

The difference in the rate of AUR between the two groups was analyzed by a two-tailed Pearson χ2-test. Patient characteristics are expressed as the mean and SD, or the range for continuous variables. The χ2 statistic was used for categorical variables, and the t-test was used for continuous variables. The effect of other variables on AUR was tested by logistic regression. Initial univariate analysis with a two-tailed Pearson χ2-test and paired or unpaired t-tests was used to identify candidate variables to enter in a backwards stepwise logistic regression. The criterion for selecting candidate variables was P < 0.20. Differences were considered significant at P < 0.05.

Results

Between April 2010 and July 2011, 236 patients were recruited and randomly assigned to one of two groups. The patient distribution is summarized in Figure 1. Demographic and baseline clinical characteristics are summarized in Table 1. At least 86% of patients in each group completed the study. No patient discontinued the study because of adverse events. There was no difference between the groups in terms of dropout, and the characteristics of the two groups were similar.

Figure 1.

Study flow diagram.

Table 1. Demographic and baseline clinical characteristics
 TamsulosinControlP-value
No. patients109109 
Age, mean ± SD (range)63.6 ± 6.663.4 ± 8.00.840
PSA, mean ± SD10.2 ± 12.28.3 ± 7.50.159
Clinical stage, n (%)  0.093
T179 (72.5)92 (84.4) 
T229 (26.6)16 (17.7) 
T31 (0.9)1 (0.9) 
Biopsy Gleason score, n (%)  0.233
6 or less44 (40.4)56 (51.4) 
740 (36.7)35 (32.1) 
8 or greater25 (22.9)18 (16.5) 
Prostate volume, mean ± SD (cc)36.1 ± 18.635.1 ± 14.00.667
IPSS questionnaire (mean ± SD)   
Total index score9.7 ± 6.910.1 ± 7.10.637
Storage subscale4.1 ± 3.04.0 ± 2.80.907
Voiding subscale5.6 ± 4.66.1 ± 5.00.448
QOL item2.1 ± 1.62.2 ± 1.70.424
ICS male SF questionnaire, mean ± SD   
Voiding sum5.7 ± 4.26.4 ± 4.90.286
Incontinence sum1.7 ± 2.12.1 ± 3.00.343
Frequency score1.4 ± 0.81.4 ± 0.80.530
Nocturia score1.5 ± 1.11.4 ± 1.10.687
QOL item0.6 ± 0.70.7 ± 0.80.395
Qmax, mean ± SD (mL/s)18.4 ± 8.017.7 ± 9.20.545
PVR, mean ± SD (mL)38.7 ± 56.328.0 ± 31.20.084
History of alpha blocker use, n (%)14 (12.8)22 (20.2)0.144
Operative experience  0.223
Early period (case 1–109)59 (54.1)50 (45.9) 
Late period (case 110–218)50 (45.9)59 (54.1) 

The overall and grouped (stratified according to the experience of the surgeon) incidence rates of AUR for each group are shown in Figure 2. After catheter removal, eight out of 109 patients (7.3%) in the tamsulosin group and 19 out of 109 patients (17.4%) in the control group developed AUR (P = 0.018). In the early period, the incidence of AUR was 10.2% in the tamsulosin group versus 30.0% in the control group (P = 0.009). Although the incidence of AUR was still higher in the control group than in the tamsulosin group in the late period, the difference was not statistically significant (P = 0.526).

Figure 2.

Overall and grouped (stratified according to the experience of the surgeon) incidence of acute urinary retention for each group (tamsulosin vs control). image, Tamsulosin; image, control.

Univariate and multivariate logistic regression analysis identified tamsulosin treatment and the experience of the surgeon as independent risk factors for AUR (Table 2). Patients who were treated with tamsulosin showed a 0.3-fold lower risk of developing AUR following catheter removal after RARP than patients in the control group (95% confidence interval 0.12–0.76; P = 0.011).

Table 2. Univariate and multivariate logistic regression models predicting acute urinary retention after urethral catheter removal
PredictorsUnivariate analysisMultivariate analysis
OR (95% CI)P-valueOR (95% CI)P-value
Tamsulosin vs control0.38 (0.16–0.90)0.0280.30 (0.12–0.76)0.011
Age (continuous variables)1.07 (1.00–1.13)0.0451.07 (1.00–1.13)0.037
Prostate volume, cc (continuous)1.01 (0.99–1.03)0.405
Maximum urinary flow rate, mL/s (continuous)0.98 (0.93–1.03)0.360
Postvoid residual volume, mL (continuous)0.99 (0.98–1.01)0.237
Baseline IPSS total index score1.07 (1.01–1.12)0.0151.05 (0.99–1.11)0.105
Operative experience (case volume, continuous)0.99 (0.98–1.00)0.0020.99 (0.98–0.99)0.001

At 2 weeks after catheter removal, the mean IPSS total, storage, voiding subscale and quality of life scores were not different between the groups (Table 3). Domain scores of the ICS male short-form questionnaire (voiding sum, incontinence sum, frequency score, nocturia score and quality of life items) did not show significant differences between the two groups. The change of the incontinence sum of the ICS male questionnaire from baseline was not significantly different between the tamsulosin and control groups (3.3 vs 3.5; P = 0.690). Uroflowmetric parameters (maximum urinary flow rate and postvoid residual volume) at 2 weeks after catheter removal and changes from baseline were not significantly different between the two groups. The incontinence symptom severity at 2 weeks after catheter removal according to ICS male short form questionnaire are presented (see Table S1, Supporting Information).

Table 3. Effect of tamsulosin treatment on patient self-reporting questionnaire results and uroflowmetric parameters at 2 weeks after catheter removal
 TamsulosinControlP-value
No. patients105102 
IPSS questionnaire at 2 weeks (mean ± SD)   
Total index score10.4 ± 6.411.8 ± 6.80.134
Storage subscale5.6 ± 3.06.4 ± 3.40.067
Voiding subscale4.8 ± 4.55.4 ± 4.40.356
QOL item2.7 ± 1.63.0 ± 1.40.119
ΔIPSS questionnaire (mean ± SD)   
Total index score0.6 ± 7.41.5 ± 7.10.394
Storage subscale1.5 ± 3.22.3 ± 3.20.074
Voiding subscale−0.9 ± 5.2−0.8 ± 5.20.922
QOL item0.6 ± 2.00.8 ± 2.00.547
ICS male SF questionnaire at 2 weeks (mean ± SD)   
Voiding sum4.3 ± 3.85.1 ± 4.30.139
Incontinence sum5.0 ± 4.45.6 ± 4.60.308
Frequency score1.9 ± 0.82.0 ± 0.70.233
Nocturia score2.0 ± 0.92.2 ± 1.10.192
QOL item1.2 ± 0.91.3 ± 0.80.377
ΔICS male SF questionnaire (mean ± SD)   
Voiding sum−1.5 ± 4.9−1.5 ± 5.60.995
Incontinence sum3.3 ± 4.43.5 ± 4.70.690
Frequency score0.5 ± 0.90.6 ± 0.80.478
Nocturia score0.5 ± 1.00.7 ± 1.00.064
QOL item0.6 ± 1.00.6 ± 0.90.963
Qmax at 2 weeks, mean ± SD (mL/s)18.6 ± 9.816.8 ± 9.00.157
Δ Qmax, mean ± SD (mL/s)0.1 ± 8.5−1.0 ± 10.50.420
PVR at 2 weeks, mean ± SD (mL)22.7 ± 29.127.1 ± 42.40.378
Δ PVR, mean ± SD (mL)−16.8 ± 62.1−1.3 ± 53.50.057

After a median follow-up duration of 17 months, distal urethral strictures were found to have occurred in five out of 218 (2.3%) patients. Compared with patients without urinary retention, patients with urinary retention showed a statistically insignificant trend toward a higher incidence of urethral stricture (7.4% vs 1.6%; P = 0.058); however, no symptomatic bladder neck contractures were noted during follow up.

Discussion

Although urethral catheterization after RP is bothersome for patients, its optimal duration after RARP without jeopardizing the outcome has not been defined.[1] Some high-volume centers remove the urethral catheter at 5–7 days after RARP, with extremely low incidence of urinary retention (<1%) after catheter removal.[16, 17] Other centers leave the catheter in place for more than 1 week, and for up to 12 days.[7, 18, 19] Although a previous retrospective study showed that tamsulosin reduces the incidence of AUR following early removal of a urethral catheter after open RP,[11] the present study is the first randomized controlled trial showing the benefits of tamsulosin treatment for reducing AUR following early catheter removal after RARP, regardless of the experience of the surgeon. Given the patient discomfort associated with catheterization, the known good safety profile of tamsulosin and its low cost, we recommend the perioperative use of tamsulosin for patients undergoing RARP for prostate cancer to reduce AUR.

The mechanism by which tamsulosin reduces the incidence of the urinary retention following urethral catheter removal after RARP is unclear; however, there are several possible explanations. First, it is reported that the ratio of subtype mRNA in male urethral muscle (100:0:0 for α1a : α1b : α1d-adrenoreceptors), including the proximal urethra, and α1a-adrenoreceptors are most likely responsible for contraction of the human urethra.[20] Second, it is well recognized that the tension of the bladder neck smooth muscle is mediated by α1a-adrenoceptors, and that alpha-receptor blockade effectively relieves primary bladder neck obstruction.[21, 22] These previous observations suggest that tamsulosin, as a selective α1a-blocker that mainly acts on α1a-adrenoreceptors, can improve bladder emptying after prostatectomy by relaxing the bladder neck and proximal urethra.

We found that the experience of the surgeon was an independent risk factor for the development of urinary retention even after adjusting for the patient age and tamsulosin treatment. As the experience of the surgeon increased, the incidence of urinary retention significantly decreased (19.3% in the first 109 cases vs 5.5% in the last 109 cases, P = 0.002). Similarly, previous studies showed decreasing surgical complication rates as the experience of the surgeon increased.[23, 24]

Although urinary retention decreased as the experience of the surgeon increased, the overall AUR rate was relatively high compared with other previous studies, even after taking surgeon experience into account.[17, 24] Although there are both unknown and possible reasons for this, the main possible reason is that the majority of patients were hospitalized before and immediately after removal of the urethral catheter. Assessing AUR was aided by using a non-invasive portable ultrasound to measure bladder volume. Therefore, patients could be diagnosed with AUR before symptoms or signs presented if the criteria for AUR were fulfilled.[15]

The reasons for the observed decrease in incidence of urinary retention with improved experience of the surgeon are not clear. It is possible that, in the early period, the surgeon might have been worried about the possibility of anastomotic urine leakage and the disruption of the anastomosis; therefore, thicker urethral and bladder neck suturing might have been carried out, which would be associated with increased postoperative tissue edema around the urethrovesical anastomosis. Furthermore, inexperienced surgeons tend to manipulate the transected bladder neck or urethra with the robotic graspers frequently during urethrovesical anastomosis. The heavy mechanical pressure by the robotic graspers might result in tissue damage, with subsequent tissue edema. Finally, in most cases, bladder neck preservation is attempted in the early period, because it can facilitate urethrovesical anastomosis without further bladder neck reconstruction or the possibility of endangering the ureter. Increased smooth muscle fiber tone in the preserved bladder neck might be associated with urinary retention after RARP. In a comparative study on the outcomes of bladder neck preservation vs the standard technique during RARP, the urinary retention rates were higher with bladder neck preservation than with the standard technique, even though bladder neck preservation is more successfully carried out in the late experience.[25]

Many men suffer from urinary incontinence after RARP. Theoretically, alpha-blockers can cause or aggravate urinary incontinence, because they relax the smooth muscle in the bladder neck and urethra. Therefore, we evaluated whether perioperative tamsulosin treatment would aggravate postprostatectomy urinary incontinence. Patient-reported impairment of continence, as measured by the IPSS or ICS male short-form questionnaires at 2 weeks after catheter removal, was not different between the tamsulosin and control groups. Therefore, it appears that routine perioperative use of tamsulosin after RARP does not impair continence.

The strengths of the present study include its prospective, randomized design; the use of a single surgeon; uniform surgical technique; and the use of self-administrated validated questionnaires to evaluate lower urinary tract symptoms before and after RARP. However, the present study had some limitations. Our results cannot be generalized to include some extremely high-volume RARP centers, because the incidence of AUR after urethral catheter removal decreases with greater surgical experience (as shown in the present study). Nevertheless, low-volume surgeons provide a large proportion of prostate cancer care, and surgeons carrying out fewer than five RP per year account for approximately half of the USA national volume (surgeons carrying out >30 procedures annually account for just 20% of the overall volume).[26-28] Considering the long learning curve for RARP, and the large proportion of low-volume surgeons, we recommend that perioperative tamsulosin treatment be used routinely in as many centers carrying out RARP as possible to reduce the urinary retention rates. Finally, our findings should be validated in other centers using various urethrovesical anastomosis techniques.

In conclusion, the results of the present study show that some patients receiving RARP for prostate cancer might have an increased risk of AUR after early urethral catheter removal. Perioperative treatment with tamsulosin in patients undergoing RARP might reduce the rate of AUR after early catheter removal, especially in the early learning period, without aggravating urinary incontinence.

Acknowledgment

This study was supported by Astellas Pharm, Co.

Conflict of interest

None declared.

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