The effectiveness of tamsulosin in Benign Prostate Hyperplasia (BPH) patients with Lower Urinary Tract Symptoms (LUTS): a multi-centre cohort retrospective study

Introduction: Lower urinary tract symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH) is a common condition in the ageing male. The first-line treatment of LUTS due to BPH is medical management with α-blockers or 5α-reductase inhibitors (5-ARIs). This study aims to analyze the effectiveness of tamsulosin to improve patients symptoms with LUTS due to BPH Methods: A cohort retrospective study was conducted among 62 respondents with BPH at dr. Soetomo Hospital and Airlangga University Hospital from 2014-2016. The data collected related to characteristics of patients were age, prostate volume, Prostate-Specific Antigen (PSA), IPSS score, IPSS voiding score, IPSS storage score, IPSS quality of life, Qmax, voided volume and post voiding residual urine (PVR). All of the data were analyzed using SPSS version 17.0 for Windows. Results: There were 62 samples with a mean age of 62.28 ± 7.3 years old. The average prostate volume was 36.09 ± 8.3 cc, and the PSA level was 2.8 ± 1.45 ng/dl. Most of the respondents were in moderate LUTS criteria (54.8%). IPSS and Qmax score significantly improved in a comparison between pre-treatment, 1 month and 3 months after treatment (p<0.01). There was no adverse event or severe side effect reported. Conclusion: Tamsulosin 0.4 mg daily resulted in statistically significant improvements of IPSS score, IPSS storage score, IPSS voiding score, IPSS Quality-of-life score, Qmax, Voided Volume and PVR through 1 month, but it also significantly improved IPSS score and uroflowmetry results in 3 months after treatment.


INTRODUCTION
Benign Prostatic Hyperplasia (BPH) and Lower urinary tract symptoms (LUTS) are progressive diseases.Treatment of LUTS patients due to BPH using α-blockers as monotherapy or in combination with 5α-reductase inhibitors (s-ARIs) is the firstline therapy. 1 LUTS prevalence caused by BPH increases along with age, moderate to severe LUTS symptoms occur in 40% man aged 60 years. 2 Several studies have shown an inverse proportion between LUTS complaints and quality of life. 1,2The goal of BPH treatment is to reduce complaints, reduce the progression of the disease, and improve the quality of life of patients.Some guidelines recommend treatment with alphablockers and 5-alpha reductase inhibitors (5ARI), as monotherapy or combined as appropriate treatment. 3amsulosin is a selective alpha 1a adrenergic receptor antagonist, which blocks adrenergic receptors causing relaxation of smooth muscle in bladder neck and prostate.Currently, in Indonesia, tamsulosin is commonly given to patients with BPH due to health insurance policy system, which only provides some medicines as choices for BPH patients such as tamsulosin, dutasteride or finasteride.This study aims to investigate the effectiveness and safety of tamsulosin as a monotherapy treatment for patients

ORIGINAL ARTICLE
with LUTS due to BPH for 3 months of therapy.The effectiveness of treatment comparatively evaluated IPSS, uroflowmetry and post-void residual urine (PVR) values before treatment and after treatment.

METHODS
This study was a cohort retrospective study, in which patients with Lower Urinary Tract Symptoms (LUTS) due to Benign Prostate Hyperplasia (BPH).This study used and analyzed data retrospectively from the medical record in RSUD dr.Soetomo from January 2014 until October 2016 and Airlangga University Hospital from January 2015 until October 2016.
Inclusion criteria in this study were patient who consumed tamsulosin 0.4 mg daily for at least 3 months, minimum patient's age was 45 years, as well as patients with mild LUTS, Moderate LUTS, and severe LUTS due to BPH.The diagnosis of BPH was confirmed by histopathology and PSA examinations, patients who had a history of urinary retention due to BPH and had performed TWOC.In our department, we obtained PSA examination for all patients with LUTS complaints or urinary retention suggestive to prostate enlargement.An indication of the prostate biopsy was PSA ≥10 ng/ml and result of a digital rectal examination suggestive of prostate cancer.Patients with PSA 4 -10 ng/ml with PSAD > 0.15 had performed a prostate biopsy.
The exclusion criteria were patients with prostate cancer, or pathology results was atypical acinus, ASAP (atypical small acinar proliferation), PIN (prostatic intraepithelial neoplasia), AAH (atypical adenomatous hyperplasia), Incomplete medical record, Patients who consumed Doxazosin, Terazosin, Sildenafil, Silodosin, Vardenafil, Alfuzosin, Dutasteride, Finasteride, Tadalafil, and Teltoradine or combination therapy.Also, patients with prior prostate surgery and LUTS due to Bladder neck stenosis, neurogenic bladder, and urethral stricture were excluded in this research.
Total IPSS Score, IPSS quality of life score, IPSS Voiding Score, IPSS Storage Score, Q max, Voided Volume, and post-void residual urine (PVR) were comparatively evaluated before treatment, 1 month after treatment, 2 months after treatment, and 3 months after treatment.
Data interval and ratio are displayed in the mean and standard deviation.Data nominal and ordinal are displayed in percentage.Data interval and ratio with normal distribution were analyzed using ANOVA test and correlation test with Pearson.Data with abnormal distribution were analyzed with Wilcoxon test and Spearman correlation test.Wilcoxon test and Spearman correlation test were used for data nominal and ordinal.We used one-way ANOVA repeated test and Friedman test to compare four groups' data before treatment, 1 month after treatment, 2 months after treatment and 3 months after treatment.Data were processed and analyzed using SPSS version 17.0.

RESULTS
We analyzed 62 LUTS patients due to BPH, with their mean age was 62.28±7.3 years old, and an average prostate volume was 36.09±8.3cc.In this study, the average PSA was 2.8 ± 1.45 ng/ dl.We found that 22.6 % of the patients has mild LUTS, 54.8 % was moderate LUTS and 22.6 % was severe LUTS.(Table 1).There was significant improvements of total IPSS, IPSS quality of life, IPSS Voiding, IPSS Storage, Q max, Voided Volume and PVR in 1 month after treatment compared to before treatment (p < 0.01), as well as 2 months after treatment compared with 1 month after treatment (p < 0.01).In comparison between 3 months and 2 months after treatment, there was a significant improvement in total IPSS, IPSS quality of life, IPSS Voiding, Q max, and PVR (p < 0.01).There were significant improvements in total IPSS, IPSS quality life, IPSS Voiding, IPSS Storage, Q max, Voided Volume and PVR 3 months after treatment compared to 1 month after treatment (p < 0.01) (Figure 1 and 2).
IPSS score, IPSS storage score, IPSS voiding score, and IPSS Quality-of-life score significantly improved in a comparison between pre-treatment, 1 month, 2 months and 3 months after treatment (p<0.01).Tamsulosin improved the Q max, voided volume and decreased the PVR volume from

ORIGINAL ARTICLE
baseline pre-treatment (p < 0.01).IPSS score, IPSS storage score, IPSS Quality-of-life score, Q max, and PVR will continue to improve until 3 months after treatment.IPSS voiding and voided volume will improve in two months after treatment (Figure 1 and 2).
There were 6 (9.6%) patients complained about retrograde ejaculation, 5 (8 %) patients complained about decreased libido, 4 (6.4%)patients had an orthostatic hypotension, 3 (4.8%) patients complained of nausea and vomiting, and 6 patients (9.6%) complained about dizziness after 1 month consuming tamsulosin 0.4 mg daily, but all of the patients had good compliance with continuing medical treatment.There was no adverse event or severe side effect reported from the patients (Table 2).
From 15 patients with previous urinary retention history, 11 patients successfully performed TWOC (Trial Without Catheter) after consuming tamsulosin 0.4 mg daily for 2 weeks before the catheter was released while 4 patients had recurrent urine retention.

DISCUSSION
There were 62 samples with an average age of 62 years and an average prostate volume of 36 cc.This result was consistent with the study conducted by Mathias Oelke et al., in which the mean age of patients with BPH was 63.5 years of age.][6][7] In this study, there was a significant improvement of total IPSS Score, IPSS quality of life score, IPSS Voiding Score, IPSS Storage Score, Q max, Voided Volume, and post voiding residual urine (PVR) in patients who had consumed tamsulosin treatment 0.4 mg daily for 1 month until 3 months in comparison with groups before treatment.It means that after patients had consumed tamsulosin 0.4 mg daily for 1 month, 2 months, and 3 months, there was an improvement of LUTS symptoms.In this study, total IPSS score significantly decreased in comparison with studies conducted by Mathias Oelke et al. with total IPSS score decreased after 3 months of tamsulosin therapy. 4ur study found a decrease in the quality of life score before treatment and decreased significantly in the 3 months of treatment.This result showed that tamsulosin could decrease the score of quality of life.This result is better than research conducted by Mathias Oelke et al., where there was an improvement in IPSS Quality of Life score with Tamsulosin 0.4 mg daily for 12 weeks.

Figure 1 .
Figure 1.The comparison score of total IPSS, IPSS quality of life, IPSS Voiding, and IPSS storage in pre-treatment, 1 month, 2 months, and 3 months following treatment (P<0.01).

2
It will increase the maximum flow rate and reduce BPH complaints.