Editorial comment on “Wada N, Kita M, Hashizume K, et al. Urodynamic effects of dutasteride add‐on therapy to alpha‐adrenergic antagonist for patients with benign prostatic enlargement: Prospective pressure‐flow study. Neurourol Urodyn 2013;32:1123–7”

Naoki Wada et al. conducted a trial on the urodynamic effects of dutasteride add-on therapy in patients with unsatisfactory symptomatic outcomes during a-blocker monotherapy. A total amount of 52 patients were prospectively investigated with filling cystometry and pressure-flow measurement at baseline and 24 weeks after initiating combination therapy. Inand exclusion criteria were very similar to those of the CombAT trial in which combination therapy proved to be more efficacious than monotherapy with a-blocker (tamsulosin) or 5a-reductase inhibitor (dutasteride) in terms of reduction of lower urinary tract symptoms (LUTS), improvement of maximum urinary flow rate (Qmax), and reduction of disease progression. Despite the short follow-up period, Wada et al. could demonstrate that combination therapy was able to significantly reduce detrusor pressure at maximum flow (Pdetqmax), bladder outlet obstruction index (BOOI), Schäfer grade of benign prostatic obstruction (linPURR), and amplitude of involuntary detrusor contractions. Moreover, they could show that 7/41 patients (17.1%) with detrusor overactivity were without involuntary detrusor contractions after 24 weeks of treatment. Presented trial results are remarkable and valuable for (1) better understanding of the mechanism of action of a-blocker and dutasteride combination therapy and (2) better selection of patients for combination therapy in the future. Until now, the urological community has believed that 5a-reductase inhibitors (i.e., dutasteride and finasteride) reduce LUTS, increase Qmax, and reduce disease progression by prostate size reduction; however, there has always been the vague suspicion that something else behind prostate size reduction is responsible for the clinical effects of 5a-reductase inhibitors. Similarly, univariate analyses of epidemiological and medical trials demonstrated that—beside patients’ age—prostate size, PSA-concentration, Qmax, post-void residual urine, and LUTS severity at baseline are all significantly associated with disease progression (acute urinary retention). However, no trial has ever investigated benign prostatic obstruction (BPO) directly or performed multivariate analyses to show the major parameter(s) of disease progression. As prostate size, PSAconcentration, Qmax, and post-void residual urine are all significantly associated with BPO it is now likely that BPO is the major contributor behind disease progression and, vice versa, reduction of BPO reduces disease progression. In line with this assumption is the fact that the prevalence of detrusor overactivity and the amplitude of involuntary detrusor contractions increase with increasing BPO grade and, after treatment of BPO, the chance of detrusor overactivity and amplitude of involuntary detrusor contraction decrease likewise. No drug alone (i.e., a-blocker, antimuscarinics, plant extracts, PDE5 inhibitors) or in combination has (consistently) shown to significantly reduce BPO grade and, therefore, prostate surgery is usually recommended in symptomatic men with relevant BPO. Previous and preliminary urodynamic results with finasteride demonstrated that this 5a-reductase inhibitor can reduce BPO after long-term treatment (4 years). The current trial results with dutasteride now confirm previous results and indicate that even patients with symptomatic BPO can be safely treated with a-blocker þ dutasteride combination therapy; furthermore, reduction of BPO appears rather quickly (6 months). If these results could be confirmed by other independent trials, even patients with severe BPO could be safely treated with combination therapy in the future avoiding numerous prostate operations. The authors of this interesting trial are to be congratulated on their scientific work and should also be encouraged to continue investigating their patients over a longer time period because previous trial results with 5a-reductase inhibitor—with or without a-blockers—indicated that there are continuous improvements of LUTS and Qmax during long-term follow-up; therefore, one would also expect continuous improvements of urodynamic parameters but this hypothesis still needs to be confirmed in long-term trials.