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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 13  |  Issue : 3  |  Page : 296-300  

Cutoff level of prostate volume to predict the efficacy of α1-D/A adrenoceptor antagonist, naftopidil


1 Department of Urology, Hokkaido Social Welfare Association Hakodate Hospital, Hokkaido, Japan
2 Department of Urology, Hokkaido Prefectural Esashi Hospital, Hokkaido, Japan
3 Okamoto Urology Clinic, Hokuto, Japan

Date of Submission11-Jun-2020
Date of Acceptance25-Aug-2020
Date of Web Publication14-Jul-2021

Correspondence Address:
Dr. Yasushi Tanuma
Department of Urology, Hokkaido Social Welfare Association Hakodate Hospital, 4-6 Komaba-Cho, Hakodate 042-0935, Hokkaido
Japan
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DOI: 10.4103/UA.UA_93_20

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   Abstract 


Introduction: In lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) patients, prostate volume (PV) at baseline affects the improvement of International Prostate Symptom Score voiding symptoms (IPSS-VS) by naftopidil (NAF), but not total IPSS (IPSS-TS). To predict the efficacy of NAF, the PV cutoff point was examined using IPSS-VS.
Materials and Methods: Seventy-seven patients with LUTS/BPH were administrated with NAF 50 mg/day for 4 weeks. Age, PV, IPSS, IPSS quality-of-life (IPSS-QoL), and maximum flow rate (MFR) were evaluated at baseline, and IPSS, IPSS-QoL, and MFR were evaluated after the treatment (at 4 weeks). Responders and nonresponders were divided by IPSS-VS at 4 weeks, and the PV cutoff point was calculated.
Results: At baseline, the mean age and PV were 70.7 ± 8.2 years (range, 54–88 years) and 43.3 ± 24.5 mL (range, 20.6–141.7 mL), respectively. After 4 weeks, area under the receiver operating characteristic curve was largest in the patients with <4 points of IPSS-VS. The best standard value to evaluate the efficacy IPSS-VS at 4 weeks was 4 points for the NAF treatment, and the best PV cutoff point was 37.3 mL (sensitivity 60.5%, specificity 71.9%).
Conclusions: PV at baseline was one of the predictive factors which affected the efficacy of NAF for IPSS-VS, and LUTS/BPH patients who had PV more than 37.3 mL indicated poor improvement of IPSS-VS, even if IPSS-TS was improved.

Keywords: Benign prostatic hyperplasia, lower urinary tract symptom, naftopidil


How to cite this article:
Tanuma Y, Tanaka Y, Okamoto T. Cutoff level of prostate volume to predict the efficacy of α1-D/A adrenoceptor antagonist, naftopidil. Urol Ann 2021;13:296-300

How to cite this URL:
Tanuma Y, Tanaka Y, Okamoto T. Cutoff level of prostate volume to predict the efficacy of α1-D/A adrenoceptor antagonist, naftopidil. Urol Ann [serial online] 2021 [cited 2021 Jul 28];13:296-300. Available from: https://www.urologyannals.com/text.asp?2021/13/3/296/321360




   Introduction Top


Prostate volume (PV) at baseline affected the long-term outcome with the treatment of α1-adrenoceptor antagonist (α1-blocker; α1-B) in lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) patients.[1],[2],[3],[4],[5],[6] PV is seemed to be a predictive factor to affect the short-term efficacy of International Prostate Symptom Score voiding symptoms (IPSS-VS) in naftopidil (NAF) treatment (50 mg/day for 4 weeks).[7] However, the PV cutoff point, which can predict the short-term efficacy of IPSS-VS, is unknown in the NAF treatment.

Hence, we examined the PV cutoff point at baseline that could predict the efficacy of NAF using IPSS-VS.


   Materials and Methods Top


The present study was conducted retrospectively, and 77 patients were enrolled by the hospital or clinic who participated in this study from July 2008 to February 2014, and all patients were given NAF 50 mg/day for 4 weeks. The inclusion criteria were the patients with a clinical diagnosis of LUTS/BPH together with age ≥50 years, PV ≥20 mL, total IPSS (IPSS-TS) ≥8, and IPSS quality-of-life (IPSS-QoL) ≥3. The following patients were excluded: prostatic cancer, bladder outlet obstruction (BOO), disease activity across multiple organs suspected serious conditions, comprehension difficulties, or serious conditions receiving α1-B for hypertension. Patients judged by the attending physician to be inappropriate were also excluded. Age and PV were evaluated at the start of treatment (baseline). IPSS, IPSS-QoL, voided volume (VV), maximum flow rate (MFR), and postvoid residual urine volume (PVR) were evaluated at baseline and 4 weeks.

For the statistical comparison between the baseline and 4 weeks, IPSS-TS, IPSS storage symptoms (IPSS-SS), IPSS-VS, and IPSS- QoL were analyzed using Wilcoxon signed-rank test, whereas VV, MFR and PVR were compared using paired t-test. The comparison between groups for PV, MFR and PVR were analyzed using Student's t-test, and others were done using Mann–Whitney U-test.

The correlation and regression of IPSS-VS at 4 weeks and change in IPSS-TS from the baseline to 4 weeks were analyzed using Spearman's rank correlation coefficient. For estimation of the PV cutoff point, the best standard value of IPSS-VS at 4 weeks was calculated using area under the receiver operating characteristic (ROC) curve. The sensitivity and specificity of PV cutoff point were evaluated using the ROC curve. The continuous values were summarized as mean ± standard deviation. All analyses were performed by SPSS version 22 (IBM Japan, Tokyo, Japan) with the two tailed, and P < 0.05 was considered statistical significance.

This study was approved by the institutional review board of Hokkaido Social Welfare Association Hakodate Hospital and obtained all participants' consent.


   Results Top


Of the 77 patients who were enrolled, six patients did not visit after 4 weeks and one patient was noncompliance. Accordingly, PV cutoff point was analyzed in a total of 70 patients. Baseline characteristics, change in subjective symptoms, and objective findings are shown in [Table 1]. Mean age and PV were 70.7 ± 8.2 years (range, 54–88 years) and 43.3 ± 24.5 mL (range, 20.6–141.7 mL), respectively.
Table 1: Baseline characteristics and changes in subjective symptoms and objective findings (n=70)

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IPSS-TS, IPSS-SS, IPSS-VS, and IPSS-QoL at 4 weeks were significantly improved as compared to the baseline; however, the changes of VV, MFR, and PVR were not statistical significance.

In the AUA guidelines, α1-Bs improve IPSS-TS by 4–6 points on an average.[8] Therefore, we presumed IPSS-VS at 4 weeks equivalent to the 4–6 points reduction in IPSS-TS from the baseline (△IPSS-TS). As shown in [Table 2], IPSS-VS at 4 weeks and △ IPSS-TS were significantly correlated (χ = 0.476, P < 0.001). The regression equation is shown below:
Table 2: International Prostate Symptom Score voiding symptoms at 4 weeks which was estimated by the equation

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IPSS-VS at 4 weeks = 0.2896 × △IPSS-TS + 6.2671.

At 4 weeks, IPSS-VS, which is equivalent to decrease of IPSS-TS (less than 4 points), was calculated according to the regression equation, and it was estimated to be less than 5.1 points.

As shown in [Table 3], Area under the ROC curve (Az) was the largest in the patients with 4 points or less of IPSS-VS at 4 weeks. ROC curve was plotted to examine the PV cutoff point [Figure 1]. The PV cutoff point which evaluated the efficacy of NAF using IPSS-VS was 37.3 mL (sensitivity 60.5%, specificity 71.9%).
Table 3: The best standard value to evaluate the efficacy of naftopidil by International Prostate Symptom Score-voiding symptoms at 4 weeks

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Figure 1: Cutoff point of PV using ROC curve. ROC: Receiver operating characteristics, PV: Prostate volume

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In the patients who had >37.3 mL of PV (Group large) and <37.3 mL (Group small), the efficacy of NAF is shown in [Table 4]. All IPSS-TS, IPSS-SS, and IPSS-VS at 4 weeks were significantly improved compared with the baseline in the Group small, whereas in the Group large, only IPSS-TS and IPSS-SS were improved significantly.
Table 4: Subgroup analyses between stratified prostate volumes by the cutoff point in the receiver operating characteristic

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   Discussion Top


In the previous investigations, PV at baseline affected the long-term outcome with the treatment of α1-B in LUTS/BPH patients.[1],[2],[3],[4],[5] The European Association of Urology guidelines show that pressure flow study is useful in the diagnosis of lower urinary tract (including bladder) functions. However, it is an invasive and serious burden for LUTS/BPH patients. If the prediction is not invasive in the efficacy, the procedure must be convenient for the patients. If a predictive factor of the efficacy is noninvasive, it must be convenient for the patients.

In the long-term pharmacotherapy, BOO often generates a treatment failure. Ultrasonography declared PV or intravesical prostatic protrusion (IPP) was the predictive factor of BOO.[5],[9],[10],[11],[12],[13] According to a multivariate logistic regression analysis, IPP is a better predictive factor of BOO in comparison with PV,[10],[11] whereas Kim et al. showed that PV was the most important independent noninvasive predictive factor of BOO, among PV, Qmax, and PVR.[12] Trumbeckas et al. showed that average/peak flow rate combined with PV could be used for the prediction of BOO.[13] Therefore, we thought that PV might be evaluated with one of predictive factors of BOO.

Conversely, it was reported that PV is negatively a predictive factor of the treatment failure in the short-term α1-B dosing.[6],[14],[15] However, IPSS-TS was improved by tamsulosin for 16 weeks in the patients with large PV as compared to those with small PV.[16] On the other hand, α1-B was effective in LUTS/BPH patients with the small PV superior to the large PV.[17],[18],[19] The discrepancy of these results can be explained that evaluations for outcomes were probably nonuniform among those investigations. Therefore, we assume that PV is considered as one of the predictive factors which affect the efficacy of α1-B at least.

It was reported that only the symptoms of hesitancy and poor flow were found to be significantly related to BOO.[20] Hence, regarding voiding symptoms, LUTS/BPH patients with small PV indicated improving IPSS-VS at 4 weeks compared with the patients with large PV in the NAF treatment, but IPSS-SS and IPSS-TS were the equal efficacy regardless of PV.[7]

In the present study, PV cutoff point was able to evaluate the efficacy of 4 weeks NAF 50 mg/day treatment using IPSS-VS. As the result, IPSS-VS at 4 weeks can potentially evaluate improvement of subjective symptoms, because IPSS-VS at 4 weeks and △ IPSS-TS were significantly correlated, and the best PV cutoff point was 37.3 mL when the patients with less than 4 points of IPSS-VS at 4 weeks were defined as effective.

However, the significantly PV cutoff point was not able to find when IPSS-TS or IPSS-SS was used as a parameter of the efficacy (data not shown). The patients with less than 37.3 mL of PV significantly improved IPSS-VS at 4 weeks in comparison with the patients who had more than 37.3 mL, whereas improvement of IPSS-TS and IPSS-SS was similar in both subgroups. Therefore, the PV cutoff point of 37.3 mL is likely appropriate in the present study. These results are supported by the previous investigation by Hong et al., who showed that predictive factors which affect the efficacy of the therapy were PV and IPSS at baseline, and the best cutoff point of the PV and IPSS was 35.65 mL and 23.5 points, respectively.[17] Moreover, in the previous studies in the different groups, the values of PV of the nonresponders by naftopidil treatment were 35.1 and 36.7 mL, respectively.[18],[19]

In the present study, there were several limitations that the cutoff point of IPP was not presented. The statistical analyses were post hoc analysis and small sample size. Therefore, the prospective study on the predictive factors in short-term efficacy of α1-B treatment is needed, particularly using easy measurement and subjective symptoms.


   Conclusion Top


IPSS-VS at 4 weeks is able to evaluate the improvement of subjective symptoms. Moreover, in the patients with more than 37.3 mL of the baseline PV, the voiding symptoms were likely to poor improvement even if subjective symptoms were significantly improved. These results are informative to reconsider the treatment strategy in LUTS/BPH patients who were given NAF for 4 weeks.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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de la Rosette JJ, Kortmann BB, Rossi C, Sonke GS, Floratos DL, Kiemeney LA. Long-term risk of re-treatment of patients using alpha-blockers for lower urinary tract symptoms. J Urol 2002;167:1734-9.  Back to cited text no. 1
    
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Hong SJ, Ko WJ, Kim SI, Chung BH. Identification of baseline clinical factors which predict medical treatment failure of benign prostatic hyperplasia: An observational cohort study. Eur Urol 2003;44:94-9.  Back to cited text no. 2
    
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Masumori N, Tsukamoto T, Horita H, Sunaoshi K, Tanaka Y, Takeyama K, et al. α1-blocker tamsulosin as initial treatment for patients with benign prostatic hyperplasia: 5-year outcome analysis of a prospective multicenter study. Int J Urol 2013;20:421-8.  Back to cited text no. 4
    
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Matsukawa Y, Takai S, Majima T, Funahashi Y, Kato M, Yamamoto T, et al. Two-year follow up of silodosin on lower urinary tract functions and symptoms in patients with benign prostatic hyperplasia based on prostate size: A prospective investigation using urodynamics. Ther Adv Urol 2018;10:263-72.  Back to cited text no. 5
    
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EAU Guidelines Management of Non-Neurogenic Male Lower Urinary Tract Symptoms (LUTS), Incl. Benign Prostatic Obstruction (BPO). Available from: https://uroweb.org/wp-content/uploads/EAU-Guidelines-on-the-Management-of-Non-Neurogenic-Male-LUTS-2019.pdf. [Last accessed on 2020 Mar 05].  Back to cited text no. 6
    
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Tanuma Y, Tanaka Y, Takeyama K, Okamoto T. Does prostate volume affect the efficacy of α1D/A: Adrenoceptor antagonist naftopidil? Urol Ann 2016;8:20-5.  Back to cited text no. 7
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AUA Practice Guidelines Committee. AUA guideline on management of benign prostatic hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. J Urol 2003;170:530-47.  Back to cited text no. 8
    
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Kim M, Cheeti A, Yoo C, Choo M, Paick JS, Oh SJ. Non-invasive clinical parameters for the prediction of urodynamic bladder outlet obstruction: Analysis using causal Bayesian networks. PLoS One 2014;9:e113131.  Back to cited text no. 12
    
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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