Platinum Priority – Editorial and Reply from Author Referring to the article published on pp. 158–165 of this issue a-Blockers and Antimuscarinics for Male Lower Urinary Tract Symptoms: The Search Goes On Christian Gratzke a, *, Karl-Erik Andersson b a Department of Urology, LMU Munich, Munich, Germany; b Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA Lower urinary tract symptoms (LUTS), including bladder storage, voiding symptoms, and postmicturition dribbling, represent a common condition in elderly men and were traditionally related to an enlarged prostate [1]. However, recent studies have shown that while prostate growth leading to bladder outlet obstruction (BOO) may contribute to the development of LUTS, other factors originating from the bladder, such as detrusor overactivity (DO), detrusor underactivity, and inflammatory processes, may be equally relevant [2]. Due to the multifactorial aetiology of the disease, various treatment strategies have been introduced for patients complaining about both bladder storage and voiding symptoms that significantly affect patients quality of life. a 1 -Adrenoceptor antagonists (a-blockers) are the most commonly used drugs in this patient cohort, causing relaxation of prostatic and urethral smooth muscle [3]. The weak correlation between LUTS and prostatic enlarge- ment and/or outflow obstruction, however, have raised interest about the functional importance of extraprostatic a-adrenoceptors in the bladder, urethra, peripheral nerve terminals, and the central nervous system in the pathogen- esis of LUTS. Simultaneously, antimuscarinic agents are still first-line therapy in patients with overactive bladder syndrome and DO. But again, the mechanism of action is a matter of debate. While it was long believed that antimuscarinic drugs mainly blocked muscarinic receptors in the detrusor muscle and, thus, acted on the efferent pathway, evidence is increasing that muscarinic receptors in the urothelium and on afferent nerves may be of functional importance. This implies that antimuscarinics may act also on afferent signalling pathways [4]. There is also a dense cholinergic innervation of the prostate, both within stromal and epithelial compartments of the prostatic gland. Functional experiments revealed that antimuscari- nics may not only modulate glandular secretion but also prostatic growth [5]. In animal experiments using outflow obstruction models, intrathecal administration of antimus- carinics led to a normalisation of urodynamic changes, implying an upregulation of central pathways in case of outflow obstruction [6]. The high prevalence and severity of storage symptoms is the basis for combining the two different drug classes in patients with male LUTS with or without BOO. Various antimuscarinic agents, including tolterodine, oxybutynine, propiverine, solifenacin, and trospium chloride, have been tested with an a-blocker. These studies, which were usually of short duration (4–12 wk) and included patients with low postvoid residual (PVR) volume (200 ml), suggested that combination therapy resulted in clinically significant improvements [7]. Equally important, no additional side effects other than those known for each single drug were observed. The pivotal concern of causing acute urinary retention (AUR) by adding an antimuscarinic agent seemed to be unjustified; the risk of AUR was found to be low. However, it appears to be hard to predict which patient would profit most from combination therapy. In a study published in this issue of European Urology, Kaplan and co-workers investigated the combination of solifenacin and tamsulosin oral controlled absorption system (TOCAS) in men with LUTS and BOO in a randomised, double-blind, parallel-group, placebo-controlled study [8]. The primary objective was to assess the noninferiority of TOCAS 0.4 mg plus solifenacin 6 mg or 9 mg versus placebo on urodynamic variables as safety measures. Inclusion criteria were an international prostate symptom score (IPSS) EUROPEAN UROLOGY 63 (2013) 166–168 available at www.sciencedirect.com journal homepage: www.europeanurology.com DOI of original article: http://dx.doi.org/10.1016/j.eururo.2012.07.003. * Corresponding author. Department of Urology, LMU Munich – Campus Grosshadern, Marchioninistr. 15, 81377 Munich, Germany. Tel. +49 89 7095 2971; Fax: +49 89 7095 8890. E-mail address: christian.gratzke@med.uni-muenchen.de (C. Gratzke). 0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.