Dutasteride, a 5-alpha reductase inhibitor, has widely used to keep improving lower urinary tract symptoms (LUTS) over a long period of time and to reduce the relative risk for urinary retention or surgery for benign prostatic enlargement (BPE) [1]. According to the nationwide survey in Japan, since the introduction of dutasteride in 2009, the surgical procedures for BPE have decreased [2]. On the other hand, dutasteride monotherapy or combination treatment with alpha-adrenergic antagonist and dutasteride is not always effective for every patient with BPE. The aim of this study was to identify the clinical factors resulting in the failure of dutasteride add-on treatment to alpha-adrenergic antagonist in patients with LUTS and BPE.

We retrospectively surveyed the patient cohort who had enrolled in the prospective study of dutasteride add-on treatment to alpha-adrenergic antagonist from December 2009 to November 2011 [3]. Inclusion criteria of the study were prostate volume (PV) ≥30 ml and the International Prostate Symptom Score (IPSS) ≥8 or IPSS-QOL ≥3 under administration of alpha-adrenergic antagonist. Treatment failure was defined as receiving surgery for BPE or requiring intermittent catheterization or permanent bladder catheter for urinary retention or huge postvoid residual urine. Clinical parameters before dutasteride add-on treatment including age, symptoms score, PV, intravesical prostatic protrusion (IPP) on ultrasonography, and urodynamic parameters [voiding efficiency, maximum flow rate (MFR), bladder outlet obstruction index (BOOI), and bladder contractility index (BCI)] were compared between the successful and failed group. The mean values between groups were statistically compared using Wilcoxon signed ranks test and square test, with P<0.05 considered to indicate statistical significance. The cut-off value was determined using Youden index on ROC curve for each clinical parameter with P<0.2 in univariate analysis. We calculated the odds ratio for each parameter using the logistic regression analysis.

Of 92 patients, 23 (25%) were defined as treatment failure at 7 to 109 months (mean: 38 months) after dutasteride add-on treatment. In the failed group, the patients’ age was younger (71.6±6.8 vs 75.4±8.4, p=0.033), PV was larger (76±41 vs 49±26 ml, p=0.005), voiding efficiency was lower (54±27 vs 68±24%, p=0.045) and BOOI was higher (73±30 vs 48±30, p=0.015) before dutasteride add-on treatment. Using logistic regression analysis, age less than 73 years old (OR 6.62, 95%CI 1.86-23.6: p=0.003), PV ≧52 ml (OR 6.48, 95%CI 1.71-24.5: p=0.006), and MFR <7.5 ml/sec (OR 7.21, 95%CI 1.78-29.2: p=0.006) were associated with treatment failure (Table).

Some patients receiving dutasteride treatment finally receive BPE surgery or bladder catheterization while previous clinical trials with dutasteride indicate the reduction of the relative risk for BPE surgery or urinary retention. Persistent LUTS refractory to medical treatment and the development of urinary retention and/or urinary tract complications (recurrent urinary tract infection or upper tract deterioration) is an indication for BPE surgery. Before and during the medical treatment for LUTS associated with BPE, patients should be provided relevant information on possible prognosis of current treatment in the long run. The present study suggests that relatively young age (<73 years old),  PV ≧52 ml, and MFR <7.5 ml/sec might be risk factors predicting a future failure of dutasteride treatment.

Age less than 73 years old, PV ≧52 ml, and MFR <7.5 ml/sec are the risk factors resulting in the unsuccessful outcome of dutasteride add-on treatment with alpha-adrenergic antagonist. This kind of information should be provided to the patients early in the clinical practice so that they could consider the necessity of BPE surgery in the long run.

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