Original Paper
Urologia Internationalis
Received: April 14, 2014 Accepted after revision: June 17, 2014 Published online: August 20, 2014
Urol Int 2014;93:338–343 DOI: 10.1159/000365335
Can We Decide the Optimal Initial Treatment for Male Lower Urinary Tract Symptoms Patients with Overactive Bladder by the Most Bothersome Symptom? A Randomized, Prospective, Open-Label Study Jong Hyun Yun a Jae Heon Kim b Jae Ho Kim a Sang Wook Lee c Hee Jo Yang d Seung Whan Doo b Won Jae Yang b b
Department of Urology, Soonchunhyang University College of Medicine, Gumi Hospital, Gumi, Seoul Hospital, Seoul, c Bucheon Hospital, Bucheon, and d Cheonan Hospital, Cheonan, South Korea
Key Words Prostatic hyperplasia · Prostatism · Outcome assessment
Abstract Objectives: To compare the treatment outcome of tamsulosin 0.4 mg (TAM) with or without solifenacin 5 mg (SOL) for the most bothersome symptom in male lower urinary tract symptoms (LUTS) with overactive bladder (OAB). Subjects and Methods: Male LUTS/OAB (≥50 years) patients who had a total International Prostate Symptom Score (I-PSS) of ≥12, I-PSS urgency-related question of ≥2, and quality of life (QoL) of ≥3 points were enrolled. Patients who complained of storage symptoms as the most bothersome were included in the ‘storage’ group. Patients who complained of voiding symptoms as the most bothersome were included in the ‘voiding’ group. The change in the I-PSS was compared between the two groups 4 weeks after commencing treatment. Results: In the storage group, 172 were able to finish this study (TAM: 88, TAM + SOL: 84). The improvement of I-PSS
© 2014 S. Karger AG, Basel 0042–1138/14/0933–0338$39.50/0 E-Mail [email protected] www.karger.com/uin
and QoL with TAM + SOL was significantly greater than with TAM alone (p < 0.001). In the voiding group, 108 were able to finish the study (TAM: 54, TAM + SOL: 54). The improvement of I-PSS and QoL with TAM alone was significantly greater than with TAM + SOL (p < 0.001). Conclusions: The most bothersome symptom in male LUTS/OAB should be considered when choosing the appropriate medical treatment. © 2014 S. Karger AG, Basel
Introduction
Since overactive bladder (OAB) symptoms may not be caused by a prostatic condition, pharmacotherapies that target only the prostate (and not the bladder) are not effective [1, 2]. Many randomized placebo-controlled trials have revealed that combination therapy with α-adrenergic antagonist and antimuscarinics have given rise to a better response in various clinical paramWon Jae Yang, MD, PhD Department of Urology, Soonchunhyang University Seoul Hospital 59, Daesagwan-ro, Yongsan-gu Seoul 140-743 (South Korea) E-Mail wonjya @ schmc.ac.kr
Downloaded by: University of Tokyo 157.82.153.40 - 5/26/2015 1:34:49 PM
a
Assessed for eligibility (n = 400) Excluded (n = 56) • Did not meet inclusion criteria (n = 46) • Declined to participate (n = 10) The most bothersome symptom (n = 344)
Storage group (n = 202) Randomized
TAM 0.4 mg
Obstructive group (n = 142) Randomized
TAM 0.4 mg
(n = 101)
TAM 0.4 mg + SOL 5 mg (n = 101)
(n = 71)
TAM 0.4 mg + SOL 5 mg (n = 71)
Withdrawals (n = 13) Lost F/U (n = 8) Declined consent (n = 5)
Withdrawals (n = 17) Lost F/U (n = 11) Declined consent (n = 6)
Withdrawals (n = 17) Lost F/U (n = 9) Declined consent (n = 8)
Withdrawals (n = 17) Lost F/U (n = 10) Declined consent (n = 7)
Efficacy analysis (n = 88)
Efficacy analysis (n = 84)
Efficacy analysis (n = 54)
Efficacy analysis (n = 54)
Fig. 1. Disposition of patients assigned to study treatment. F/U = Follow-up.
eters including those assessed with subjective and objective scales than α-adrenergic antagonist monotherapy in male lower urinary tract symptoms (LUTS) with OAB patients [3–5]. The primary goal for treating men with clinical manifestations related to LUTS is usually to reduce or, ideally, to relieve the bothersome symptoms. Patients often consult their physician due to 1 or 2 symptoms that they find obnoxious. The patient’s views must be carefully elicited and incorporated into the treatment plan, and the LUTS severity assessment needs to be augmented with information on the most bothersome symptom, which should drive the decision-making process in LUTS management [6, 7]. Lee et al. [8] reported that assessing goal achievement for the most bothersome symptom can be a useful outcome measure in male patients with LUTS. Our hypothesis was that the initial treatment decision whether to choose combination (α-adrenergic antagonists + anticholinergics) or monotherapy (α-adrenergic antagonists)
in male LUTS/OAB patients could be based on the patients’ most bothersome symptom. The goal of the current study is to compare the treatment outcome of tamsulosin 0.4 mg (TAM) with or without solifenacin 5 mg (SOL) for the most bothersome symptom in male LUTS/OAB patients.
TAM with or without SOL for the Most Bothersome Symptom
Urol Int 2014;93:338–343 DOI: 10.1159/000365335
Subjects and Methods
339
Downloaded by: University of Tokyo 157.82.153.40 - 5/26/2015 1:34:49 PM
Patients and Study Design This prospective, randomized, open-label, and non-placebo-controlled study recruited patients from urology clinics of 4 referral hospitals in South Korea. Patients presenting with LUTS were screened for eligibility. Eligible patients were men ≥50 years, a total International Prostate Symptom Score (I-PSS) of ≥12 points, an urgencyrelated question in I-PSS of ≥2 points, and an I-PSS quality of life (QoL) of ≥3 points. Exclusion criteria included postvoiding residuals of ≥100 ml, prostate-specific antigen ≥10 ng/ml, some neurologic conditions (e.g. spinal cord injury, diabetes mellitus neuropathy), prostate cancer, prostate surgery or other intervention, radiation
Table 1. Baseline demographics and clinical characteristics
Storage group
Age, years Prostate size, ml Qmax PV Total I-PSS Storage subscale Voiding subscale QoL
Voiding group
TAM (n = 88)
TAM + SOL (n = 84)
TAM (n = 54)
TAM + SOL (n = 54)
61.86 ± 6.60 43.50 ± 14.59 10.21 ± 2.34 34.30 ± 34.64 18.31 ± 4.66 7.90 ± 2.49 10.42 ± 4.32 4.32 ± 0.65
61.67 ± 6.97 41.39 ± 13.90 9.84 ± 3.12 28.50 ± 40.31 19.95 ± 5.20* 9.05 ± 2.46** 10.89 ± 3.70 4.33 ± 0.72
61.85 ± 8.90 43.46 ± 12.37 11.27 ± 2.56 35.25 ± 21.52 19.87 ± 5.05 7.63 ± 2.51 12.24 ± 4.55 4.0 ± 0.91
61.61 ± 7.48 45.06 ± 14.96 10.35 ± 2.87 40.21 ± 36.34 20.42 ± 6.44 7.98 ± 2.64 12.39 ± 4.50 4.22 ± 0.79
All data are shown as means ± SD. * p < 0.05; ** p < 0.01. Qmax = Maximal urinary flow rate; PV = postvoiding residual volume.
Outcome Measurement The primary endpoint was to compare the effectiveness of TAM alone or TAM + SOL in each treatment group at week 4 in terms of symptom reduction with I-PSS. Secondary endpoints were changes in the QoL and storage and voiding subscales between baseline and week 4. Statistical Analysis The baseline characteristics and improvements in the various parameters were compared using paired and independent t tests. p < 0.05 was considered to indicate statistical significance. All analyses were performed with SPSS version 14.0 for Windows (SPSS Inc., Chicago, Ill., USA).
Results
Patients were recruited between February 2012 and August 2013. A total of 344 patients were included and entered into either the storage or voiding group according to the most bothersome symptom the patient complained of. Patient disposition is summarized in figure 1. 340
Urol Int 2014;93:338–343 DOI: 10.1159/000365335
Table 2. Storage group: treatment outcome at week 4
TAM (n = 88) Total I-PSS Storage subscale Voiding subscale QoL
TAM + SOL (n = 84)
–5.77 ± 4.79 –2.98 ± 2.41 –3.10 ± 3.30 –1.14 ± 0.71
p
–8.10 ± 3.93 –4.48 ± 2.33 –3.75 ± 2.40 –1.48 ± 0.91
Urologia Internationalis
Received: April 14, 2014 Accepted after revision: June 17, 2014 Published online: August 20, 2014
Urol Int 2014;93:338–343 DOI: 10.1159/000365335
Can We Decide the Optimal Initial Treatment for Male Lower Urinary Tract Symptoms Patients with Overactive Bladder by the Most Bothersome Symptom? A Randomized, Prospective, Open-Label Study Jong Hyun Yun a Jae Heon Kim b Jae Ho Kim a Sang Wook Lee c Hee Jo Yang d Seung Whan Doo b Won Jae Yang b b
Department of Urology, Soonchunhyang University College of Medicine, Gumi Hospital, Gumi, Seoul Hospital, Seoul, c Bucheon Hospital, Bucheon, and d Cheonan Hospital, Cheonan, South Korea
Key Words Prostatic hyperplasia · Prostatism · Outcome assessment
Abstract Objectives: To compare the treatment outcome of tamsulosin 0.4 mg (TAM) with or without solifenacin 5 mg (SOL) for the most bothersome symptom in male lower urinary tract symptoms (LUTS) with overactive bladder (OAB). Subjects and Methods: Male LUTS/OAB (≥50 years) patients who had a total International Prostate Symptom Score (I-PSS) of ≥12, I-PSS urgency-related question of ≥2, and quality of life (QoL) of ≥3 points were enrolled. Patients who complained of storage symptoms as the most bothersome were included in the ‘storage’ group. Patients who complained of voiding symptoms as the most bothersome were included in the ‘voiding’ group. The change in the I-PSS was compared between the two groups 4 weeks after commencing treatment. Results: In the storage group, 172 were able to finish this study (TAM: 88, TAM + SOL: 84). The improvement of I-PSS
© 2014 S. Karger AG, Basel 0042–1138/14/0933–0338$39.50/0 E-Mail [email protected] www.karger.com/uin
and QoL with TAM + SOL was significantly greater than with TAM alone (p < 0.001). In the voiding group, 108 were able to finish the study (TAM: 54, TAM + SOL: 54). The improvement of I-PSS and QoL with TAM alone was significantly greater than with TAM + SOL (p < 0.001). Conclusions: The most bothersome symptom in male LUTS/OAB should be considered when choosing the appropriate medical treatment. © 2014 S. Karger AG, Basel
Introduction
Since overactive bladder (OAB) symptoms may not be caused by a prostatic condition, pharmacotherapies that target only the prostate (and not the bladder) are not effective [1, 2]. Many randomized placebo-controlled trials have revealed that combination therapy with α-adrenergic antagonist and antimuscarinics have given rise to a better response in various clinical paramWon Jae Yang, MD, PhD Department of Urology, Soonchunhyang University Seoul Hospital 59, Daesagwan-ro, Yongsan-gu Seoul 140-743 (South Korea) E-Mail wonjya @ schmc.ac.kr
Downloaded by: University of Tokyo 157.82.153.40 - 5/26/2015 1:34:49 PM
a
Assessed for eligibility (n = 400) Excluded (n = 56) • Did not meet inclusion criteria (n = 46) • Declined to participate (n = 10) The most bothersome symptom (n = 344)
Storage group (n = 202) Randomized
TAM 0.4 mg
Obstructive group (n = 142) Randomized
TAM 0.4 mg
(n = 101)
TAM 0.4 mg + SOL 5 mg (n = 101)
(n = 71)
TAM 0.4 mg + SOL 5 mg (n = 71)
Withdrawals (n = 13) Lost F/U (n = 8) Declined consent (n = 5)
Withdrawals (n = 17) Lost F/U (n = 11) Declined consent (n = 6)
Withdrawals (n = 17) Lost F/U (n = 9) Declined consent (n = 8)
Withdrawals (n = 17) Lost F/U (n = 10) Declined consent (n = 7)
Efficacy analysis (n = 88)
Efficacy analysis (n = 84)
Efficacy analysis (n = 54)
Efficacy analysis (n = 54)
Fig. 1. Disposition of patients assigned to study treatment. F/U = Follow-up.
eters including those assessed with subjective and objective scales than α-adrenergic antagonist monotherapy in male lower urinary tract symptoms (LUTS) with OAB patients [3–5]. The primary goal for treating men with clinical manifestations related to LUTS is usually to reduce or, ideally, to relieve the bothersome symptoms. Patients often consult their physician due to 1 or 2 symptoms that they find obnoxious. The patient’s views must be carefully elicited and incorporated into the treatment plan, and the LUTS severity assessment needs to be augmented with information on the most bothersome symptom, which should drive the decision-making process in LUTS management [6, 7]. Lee et al. [8] reported that assessing goal achievement for the most bothersome symptom can be a useful outcome measure in male patients with LUTS. Our hypothesis was that the initial treatment decision whether to choose combination (α-adrenergic antagonists + anticholinergics) or monotherapy (α-adrenergic antagonists)
in male LUTS/OAB patients could be based on the patients’ most bothersome symptom. The goal of the current study is to compare the treatment outcome of tamsulosin 0.4 mg (TAM) with or without solifenacin 5 mg (SOL) for the most bothersome symptom in male LUTS/OAB patients.
TAM with or without SOL for the Most Bothersome Symptom
Urol Int 2014;93:338–343 DOI: 10.1159/000365335
Subjects and Methods
339
Downloaded by: University of Tokyo 157.82.153.40 - 5/26/2015 1:34:49 PM
Patients and Study Design This prospective, randomized, open-label, and non-placebo-controlled study recruited patients from urology clinics of 4 referral hospitals in South Korea. Patients presenting with LUTS were screened for eligibility. Eligible patients were men ≥50 years, a total International Prostate Symptom Score (I-PSS) of ≥12 points, an urgencyrelated question in I-PSS of ≥2 points, and an I-PSS quality of life (QoL) of ≥3 points. Exclusion criteria included postvoiding residuals of ≥100 ml, prostate-specific antigen ≥10 ng/ml, some neurologic conditions (e.g. spinal cord injury, diabetes mellitus neuropathy), prostate cancer, prostate surgery or other intervention, radiation
Table 1. Baseline demographics and clinical characteristics
Storage group
Age, years Prostate size, ml Qmax PV Total I-PSS Storage subscale Voiding subscale QoL
Voiding group
TAM (n = 88)
TAM + SOL (n = 84)
TAM (n = 54)
TAM + SOL (n = 54)
61.86 ± 6.60 43.50 ± 14.59 10.21 ± 2.34 34.30 ± 34.64 18.31 ± 4.66 7.90 ± 2.49 10.42 ± 4.32 4.32 ± 0.65
61.67 ± 6.97 41.39 ± 13.90 9.84 ± 3.12 28.50 ± 40.31 19.95 ± 5.20* 9.05 ± 2.46** 10.89 ± 3.70 4.33 ± 0.72
61.85 ± 8.90 43.46 ± 12.37 11.27 ± 2.56 35.25 ± 21.52 19.87 ± 5.05 7.63 ± 2.51 12.24 ± 4.55 4.0 ± 0.91
61.61 ± 7.48 45.06 ± 14.96 10.35 ± 2.87 40.21 ± 36.34 20.42 ± 6.44 7.98 ± 2.64 12.39 ± 4.50 4.22 ± 0.79
All data are shown as means ± SD. * p < 0.05; ** p < 0.01. Qmax = Maximal urinary flow rate; PV = postvoiding residual volume.
Outcome Measurement The primary endpoint was to compare the effectiveness of TAM alone or TAM + SOL in each treatment group at week 4 in terms of symptom reduction with I-PSS. Secondary endpoints were changes in the QoL and storage and voiding subscales between baseline and week 4. Statistical Analysis The baseline characteristics and improvements in the various parameters were compared using paired and independent t tests. p < 0.05 was considered to indicate statistical significance. All analyses were performed with SPSS version 14.0 for Windows (SPSS Inc., Chicago, Ill., USA).
Results
Patients were recruited between February 2012 and August 2013. A total of 344 patients were included and entered into either the storage or voiding group according to the most bothersome symptom the patient complained of. Patient disposition is summarized in figure 1. 340
Urol Int 2014;93:338–343 DOI: 10.1159/000365335
Table 2. Storage group: treatment outcome at week 4
TAM (n = 88) Total I-PSS Storage subscale Voiding subscale QoL
TAM + SOL (n = 84)
–5.77 ± 4.79 –2.98 ± 2.41 –3.10 ± 3.30 –1.14 ± 0.71
p
–8.10 ± 3.93 –4.48 ± 2.33 –3.75 ± 2.40 –1.48 ± 0.91
