Background: The present study assessed the long-term efficacy (>12 months) of tamsulosin in 123 patients with lower urinary tract symptoms caused by benign prostatic hyperplasia (BPH).
Methods: The patients received a starting dose of tamsulosin of 0.2 mg/day, with a further titration up to 0.4 mg/day until symptom relief. Subjective and objective clinical variables were assessed using the international prostate symptom score (IPSS), IPSS quality of life (QoL) score, BPH impact index score, peak urinary flow rate (Qmax) and postvoid residual urine volume.
Results: Except for Qmax, all clinical variables showed significant sustained improvements from baseline throughout the study period (median follow up, 43 months). Thirty patients (24.4%) withdrew because of surgical interventions. The Cox proportional hazards model showed that a baseline IPSS total score ≥15 (HR [hazard ratio] 2.13; 95% CI 1.04–4.34) was predictive of failure for tamsulosin therapy. Furthermore, during the first 12 months, a lowest IPSS total score ≥13 (HR 2.34; 95% CI 1.12–4.89), a lowest IPSS QoL score ≥3 (HR 4.16; 95% CI 1.26–13.68), and a lowest BPH impact index score ≥4 (HR 3.54; 95% CI 1.62–7.75) were also predictive of failure for tamsulosin therapy.
Conclusions: Tamsulosin treatment of BPH patients for more than 12 months showed a sustained, stable efficacy. Patients without short-term effects were prone to withdraw from tamsulosin therapy, but so did patients with a high baseline IPSS total score, even if therapy was effective for at least 12 months.
Benign prostatic hyperplasia (BPH) is a common disease in elderly men. Although many treatment methods have been developed for BPH, pharmacological therapy should be considered as the first-line treatment for patients with uncomplicated BPH. Alpha 1-adrenoceptor antagonists act on the smooth muscle fibers in the prostate and bladder neck to reduce muscle tone and relieve lower urinary tract symptoms (LUTS) caused by BPH.1–3 Tamsulosin is an alpha 1-adrenoceptor antagonist that selectively blocks alpha 1a-adrenoceptors.4,5 Tamsulosin is used worldwide as a treatment for symptomatic BPH. However, although previous studies have shown the effectiveness and safety of tamsulosin,4,5 the clinical outcome of its long-term administration is still unknown.6 In the present study, we assessed the long-term (>12 months) efficacy of tamsulosin therapy and we attempted to elucidate the predictors for failure of tamsulosin treatment in patients who required interventional therapies.
Materials and methods
Between 1993 and 1999, 123 patients with BPH who had been treated with tamsulosin for periods longer than 12 months were prospectively enrolled in the present study. Patient age ranged from 53 to 88 years (median 68, mean 67.4). BPH was diagnosed from clinical history, subjective and objective symptoms, digital rectal examination and transabdominal ultrasonography determining the prostate volume. Serum prostate-specific antigen (PSA) levels were measured and all patients with an abnormal PSA level or abnormal findings with the digital rectal examination underwent a non-systematic needle biopsy of the prostate to exclude those patients with prostate cancer. Any patients with conditions causing urinary symptoms or a reduced urinary flow rate (e.g. cystitis, prostatitis, lithiasis, urothelial malignancies and evident neurogenic bladder, a history of surgical treatment for BPH, drug treatments affecting urination such as anticholinergic agents, and other conditions causing urinary symptoms such as urethral stricture) were excluded. The baseline characteristics of patients are shown in Table 1.
Table 1. Baseline characteristics (n = 123)
Mean ± SD
BPH, benign prostatic hyperplasia; IPSS, international prostate symptom score; PSA, prostatic specific antigen; QoL, quality of life.
67.4 ± 6.6
Prostate volume (cm3)
39.6 ± 18.9
3.1 ± 3.9
16.1 ± 6.2
4.4 ± 0.9
BPH impact index score
4.4 ± 2.9
Peak urinary flow rate (mL/s)
8.9 ± 5.4
Postvoid residual urine volume (mL)
47.9 ± 53.9
The patients were treated with tamsulosin at a dose of 0.2 mg/day; this dose could be titrated up to 0.4 mg/day according to the evolution of symptoms, or reduced or discontinued in case of adverse events. Urinary symptoms were assessed using the international prostate symptom score (IPSS), the IPSS quality of life (QoL) score and the BPH impact index score.7 These three scores, together with uroflow variables (maximum urinary flow rate [Qmax] and postvoid residual urine), were assessed at baseline, after 1, 3 and 6 months, and then every 6 months thereafter. Postvoid residual urine was measured mainly using transabdominal ultrasonography. The voiding symptom subscore (sum of the scores for questions 1, emptying; 3, intermittency; 5, weak stream; and 6, hesitancy) and the filling symptom subscore (sum of the scores for questions 2, voiding frequency; 4, urgency; and 7, nocturia), together with the total IPSS score, were used for analysis.
Of the 123 patients, 30 patients (24.4%) withdrew from the study because of invasive therapy (transurethral resection of the prostate [TURP], interstitial laser coagulation and transurethral microwave thermotherapy) during the follow-up period, although they continued receiving tamsulosin therapy for at least 12 months. We attempted to detect some predictors of failure for tamsulosin treatment by comparing the variables of these 30 patients with those of the remaining 93 patients.
Changes from baseline for each variable were analyzed using the Wilcoxon signed rank test. The Mann–Whitney U-test was used to analyze the differences between groups for each variable. The tamsulosin failure-free rate was estimated using Kaplan–Meier plots. The Cox proportional hazard analysis was used to detect the predictors of failure for tamsulosin therapy. P-values <0.05 were considered significant.
One hundred and seven patients (87.0%) received 0.2 mg/day of tamsulosin and 16 patients (13.0%) received 0.4 mg/day during a median follow-up period of 43 months. At all follow-up intervals, the IPSS total score, voiding symptom subscore, filling symptom subscore, IPSS QoL score and BPH impact index score were significantly lower than at baseline (Fig. 1). Furthermore, a significant decrease in postvoid residual urine volume was observed throughout the study period. A significant increase in peak urinary flow rate (Qmax) was measured during the first 18 months, but there were no significant differences at 24 months or later.
Eighteen patients (14.6%) required additional medications including other alpha 1-adrenoceptor antagonists, anticholinergic agents and herbal medicines during follow up. Three (16.7%) of these 18 patients underwent surgical therapy thereafter. Average time to additional medication was 33 months.
Thirty patients (24.4%) withdrew from the study because of surgical interventions during follow up. Nine patients underwent TURP, two patients underwent interstitial laser coagulation, 17 patients underwent transurethral microwave thermotherapy, and two patients underwent other transurethral treatment. Average time to surgical intervention was 30 months. No patients withdrew from tamsulosin therapy because of adverse events. The tamsulosin failure-free rate is shown in Figure 2.
The univariate analysis using the Cox proportional hazards model showed the following risk factors for failure of tamsulosin therapy: a baseline IPSS total score ≥15 and, during the first 12 months, a lowest IPSS total score ≥13, a lowest IPSS QoL score ≥3, and a lowest BPH impact index score ≥4 (Table 2). With the multivariate analysis, a baseline IPSS total score ≥15 and a lowest IPSS QoL score ≥3 during the first 12 months were the statistically significant risk factors (Table 3). Figure 3 shows the tamsulosin failure-free rate stratified by baseline IPSS. Other baseline parameters, such as age, prostate volume, QoL score and BPH impact index were non-significant. Neither Qmax nor postvoid residual urine was a significant risk factor. The sequential changes in the IPSS total scores, IPSS QoL score and BPH impact index score of the tamsulosin-continuing group and the failure group are shown in Figure 4.
Table 2. Cox univariate analysis of various parameters as predictors for tamsulosin failure (n = 30)
Hazard ratio (95% CI)
BPH, benign prostatic hyperplasia; IPSS, international prostate symptom score; ns, not significant; QoL, quality of life.
Prostate volume (cm3)
IPSS QoL score
BPH impact index score
Highest IPSS score during the first 12 months
Highest QOL score during the first 12 months
Highest BPH impact index score during the first 12 months
Table 3. Multivariate analysis with Cox proportional hazards model for predicting tamsulosin failure
Hazard ratio (95% CI)
IPSS, international prostate symptom score; QoL, quality of life.
Baseline IPSS score
Highest QOL score during the first 12 months
Many treatment methods for BPH have been developed during recent years. Although our previous studies showed that several invasive treatments considerably reduced the symptoms and increased the QoL of BPH patients,8–10 conservative therapies including observation and pharmacotherapy should be initially considered. Selective alpha 1-adrenoceptor antagonists, including tamsulosin, are often used for the treatment of symptoms of BPH all over the world. Tamsulosin shows a fast and pronounced effect on improving urinary symptoms.5 Many studies have shown a good efficacy and tolerability.4,11–19 Most of these studies were conducted on a short-term basis. The findings of the present study agree with the suggestion raised in previous studies that tamsulosin might be equally effective even when administered for long periods of time.12,13,16,17 The administration of tamsulosin was effective during a long-term follow up of up to 102 months. A total of 30 patients (24.4%) withdrew because of interventional treatment during the follow-up period of the present study, even though they had responded to tamsulosin therapy for at least 12 months. We excluded patients who discontinued tamsulosin therapy within 1 year; therefore, the failure rate of tamsulosin therapy within 1 year must have been higher than the data shown here.
Multiple factors can affect the failure of tamsulosin treatment. Socioeconomic status, education, marital status, living area, other complications, performance status and other medications might be contributing factors. In the present study, however, we confined discussion to objective and subjective urinary parameters and pursued the possibility of detecting failure of long-term treatment with tamsulosin using these variables.
Rosette et al. reported that the re-treatment rate with tamsulosin was 27% at 3-year follow up.20 Their study revealed that severe symptoms like poor urinary flow, enlarged prostate volume and urodynamically proven bladder outlet obstruction increased the chance of re-treatment. The findings of the present study partially agree with their study. Our study showed that patients with a higher IPSS total score at baseline and patients showing no short-term effect on the IPSS total score, IPSS QoL score and BPH impact index score were likely to discontinue the interventional treatment during follow up, even after 1 year. Other parameters, such as age, prostate volume, baseline QoL score and BPH impact index, lacked statistical significance; this might be partly due to a small sample size. Alternatively, our data also suggest that for selected patients, long-term tamsulosin therapy is a good treatment option for symptomatic BPH.
Because BPH is rarely a life-threatening disease, various issues, including quality of life and cost-effectiveness, should be simultaneously considered at the time of beginning, continuing and changing treatments. From a cost-effective point of view, it might be prudent to perform an interventional therapy earlier if we can detect which patient is likely to be refractory to conservative treatment. Therefore, it is quite important to find out which factors predict treatment failure. The present study might provide valuable information for BPH treatment in clinical practice.