Shock wave lithotripsy (SWL) and ureteroscopy are effective instrumental treatments for ureteral stones. However, the possible morbidity, significant cost and the need for highly specialized equipment and special expertise raise the question whether these treatments are indeed the most attractive options to meet the increasing demand. One may conclude ‘yes’ since the classic conservative treatment with hydration and non-steroidal anti-inflammatory drugs such as indomethacin alone is insufficient to yield rapid stone expulsion and to prevent colic and pain. Since non-interventional treatments are the most appealing to patients, however, there is a large interest in alternative medical treatment modalities. One possible pathway for medical treatment is anti-inflammatory and anti-oedematous treatment by glucocorticoids. Another option is the relaxation of ureteral smooth muscle (eg, by α1-adrenoceptor antagonists (α-blockers) or Ca2+ entry blockers. A study [1] in this issue of the journal has investigated the individual contributions of an α-blocker, a glucocorticoid and their combination in the expulsive therapy for distal ureter stones, on the basis of several previous studies that have tested α-blockers when given on top of glucocorticoids such as deflazacort [2], [3], [4], [5].

While the available studies on the use of α-blockers in the treatment of urolithiasis did not always reach statistical significance with regard to overall expulsion rates, they have consistently shown α-blockers to be more effective than standard treatments with regard to expulsion time, colic episodes, pain, use of analgesics and quality of life [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. Such beneficial effects were observed not only in patients receiving medical treatment only, but also in combination with extracorporeal SWL [7], [8], [9]. In this regard, the addition of an α-blocker to SWL was particularly effective in patients with a stone diameter of more than 10mm [8]. All currently available studies on the α-blocker treatment of urolithiasis have used tamsulosin, possibly because of its excellent tolerability and the lack of need for dose titration upon initiation of treatment, which allows administering a fully effective dose right away. However, limited direct comparative data indicate that doxazosin and terazosin can be similarly effective [11].

When taken together, these data clearly demonstrate that α-blockers can be used safely and effectively in the treatment of urolithiasis. The key questions in this regard are how the efficacy and safety of α-blockers relate to those of other treatments and whether combination of mechanistically distinct approaches may yield superior benefit. In this regard, some studies indicate that tamsulosin is more effective, at least for some parameters, than the Ca2+ entry blocker nifedipine [3], [5]. With regard to a possible combination with glucocorticoids, several previous studies had used tamsulosin on top of a glucocorticoid, mostly deflazacort [2], [3], [4], [5]. In this issue of the journal, a four-way comparison is made between standard treatment (fluid intake of at least 2 l a day and the analgesic diclofenac on demand), deflazacort, tamsulosin and a combination of the latter two [1]. While the glucocorticoid alone had only little effect, compared with the control group, it significantly enhanced the beneficial effects of tamsulosin on expulsion rate, overall stone expulsion, analgesics use and need for secondary ureteroscopies. Most importantly, at least within this study, the overall expulsion rate was 100% (33 of 33 patients) upon combination treatment. On the basis of these studies, it appears useful to combine an α-blocker with a glucocorticoid in the medical treatment of urolithiasis or as an adjunct to SWL, with the combination of tamsulosin and deflazacort being best documented in the literature.

The present study, focusing on distal stones, should also be put within the perspective of treating ureteral stones throughout the entire ureter. About 30% of stones are located in the proximal ureter, and expulsion of these stones is less favourable than distal ureter stones. On a conceptual base, one would expect that α-blockers may facilitate stone expulsion in these cases, but this hypothesis needs to be tested. Moreover, the treatment of ureteral stones in special situations, such as patients at high risk for surgery or pregnant patients, may be considered for future research in this field.

Interestingly, the development of α-blockers for the treatment of urolithiasis apparently has occurred largely independently from the pharmaceutical industry, possibly because of a perceived insufficient economic potential in such an indication. While collaboration between urologists and the pharmaceutical industry clearly is desirable, many other potential indications exist, in which pharmaceutical companies show insufficient interest and/or their interests diverge from those of urologists and their patients. Therefore, the success story of α-blockers for the treatment of urolithiasis contains a number of interesting lessons.

While the above studies are scientifically interesting and clinically relevant, they also have limitations. For example, few studies in this field have had vigorous randomization procedures, and none of them has been performed in a double-blind, placebo-controlled manner. Moreover, all studies apparently are from single centres, which yield relatively low patient numbers with limited statistical power and may affect the ability to extrapolate their findings to the patient population at large. Finally, not all studies systematically report on the side effects of the administered treatment regimens. Therefore, they fall short of the technical quality we know from industry-sponsored studies and may generate a lower grade of evidence. This observation is not meant as a criticism of the spearheading efforts of the investigators in those studies, who can only be congratulated for their activities; rather, it largely reflects that investigator-initiated studies lack the financial resources and technical infrastructure of large pharmaceutical companies. Since such investigator-initiated studies are a cornerstone of the future of academic urology, it appears a worthwhile task for professional organizations such as the European Association of Urology to create the networks and infrastructures along with suitable training to allow even better industry-independent studies on new medical treatment modalities in the future.