EURURO Vol. 71 No. 4

505 692

about the effectiveness of a -blockers. A debate began about
the usefulness of MET for conservative management of
ureteral stones. This paper summarizes the actual evidence
and the related panel and point–counterpoint discussions
from the European Association of Urology (EAU) and
American Urological Association (AUA) annual meetings
and develops a current treatment recommendation.
Searches were carried out using the Cochrane Library
Database of Systematic Reviews, the Cochrane Library of
Controlled Clinical Trials, Medline, and Embase on the
Dialog–Datastar platform up to April 2016. The focus of the
searches was identification of meta-analyses of randomized
controlled trials (RCTs). In addition, the search was
extended to multicenter double-blinded placebo-controlled
randomized trials involving >200 patients. They were
selected because small single-center RCTs were included in
the meta-analyses, and the authors were aware that small
single-center RCTs tend to show larger treatment effects
than multicenter RCTs usually do .
1. Evidence from meta-analyses
Various meta-analyses support the use of MET for ureteral
stone management. Hollingsworth et al included
693 patients from nine trials and found that patients given
calcium channel blockers or a-blockers had a 65% greater
likelihood of stone passage compared with those without
MET.
Seitz et al pooled 2419 patients in a meta-analysis of
47 RCTs assessing the role of different substances evaluated
for MET; only a-blockers and calcium channel blockers
demonstrated higher and faster expulsion rates compared
with controls, suggesting that MET with a-blockers or
calcium channel blockers improves stone expulsion rates,
reduces the time to stone expulsion, and reduces analgesic
requirements for ureteral stones 10 mm In another
meta-analysis focusing on a-blockers only, Campschroer
et al compared a-blockers with alternative medications and
placebo; they included 32 randomized trials with a total of
5864 participants and showed a noticeably shorter stone
expulsion time with fewer pain episodes for MET with a-
blockers .
Focusing on the comparison of an a-blocker (tamsulosin)
and a calcium channel blocker (nifedipine), Wang et al
performed a comprehensive search and meta-analysis
including 12 RCTs with 4961 patients; they calculated a
higher expulsion rate with the use of tamsulosin (risk ratio:
1.29; 95% confidence interval [CI], 1.25–1.33), reduced
expulsion time (standard mean difference: 0.39; 95% CI,
0.72 to 0.05), and fewer complications compared with
nifedipine and concluded that tamsulosin showed overall
superiority to nifedipine .
In a recent systematic review and meta-analysis, O¨ zsoy
et al compared two a-blockers, silodosin and tamsulosin, as
MET. They included three RCTs, two of themdouble blinded,
and showed significantly higher stone expulsion rates and
faster expulsion times in favor of silodosin compared with
tamsulosin .
A major problem with most studies included in meta-
analyses performed to date is the difference in primary
outcomes used and the lack of information about how
outcomes were measured. Stone passage rate and stone
expulsion time are described in many studies, but it is not
clear how they were measured (very few studies used
computed tomography [CT] imaging, and expulsion time
relied on patient recall).
2. Evidence from large placebo-controlled double-
blinded randomized multicenter trials
In 2015, Pickard et al published a large, multicentric,
double-blinded, three-way RCT comparing tamsulosin,
nifedipine, and placebo. The authors defined as their
primary end point the necessity of interventional stone
removal and involved 1167 patients in 24 UK hospitals. The
authors noticed no difference among tamsulosin, nifedi-
pine, and placebo in terms of need for intervention, stone
passage rate, or pain reduction . Furyk et al recently
performed a randomized, double-blinded, placebo-con-
trolled, multicenter trial including 403 patients to compare
tamsulosin and placebo for patients with distal ureteral
stones only and stone size up to 10 mm. Only the subgroup
analysis of stones 5–10 mm showed an increased passage
rate in the tamsulosin group; in the overall analysis and in
the subgroup of stones <5 mm, there was no significant
difference .
A double-blinded study by Sur et al involving 27 locations
randomized 246 patients to silodosin or placebo. There was
no statistically significant difference in terms of overall
stone passage, but the passage rate of distal ureteral stones
was significantly higher with silodosin than placebo (69% vs
46%, respectively) .
3. Guidelines and medical expulsive therapy
In 2007, the EAU and AUA cooperative working group on
guidelines on ureteral stones performed and published a
meta-analysis of MET. The conclusions drawn were that
a-blockers facilitate stone passage, that the positive impact
of nifedipine was marginal, and that a-blockers may be the
preferred agents for MET .
In 2016, the AUA published new guidelines on the
management of ureteral stones. Based on its own meta-
analysis focusing on distal ureteral stones <10 mm
(n = 1215; 27 papers included, mean number of patients
was 45), the AUA panel showed superior stone-free rates for
those patients treated with a-blockers (77.3%) compared
with placebo or no treatment (54.4%) This resulted in a
statement that patients with uncomplicated ureteral stones
<10 mm should be offered observation, and those with
distal stones of similar size should be offered MET with a-
blockers. Due to insufficient data, the AUA panel did not
endorse calcium channel blockers as MET
Through the years, the EAU guidelines on urolithiasis
reported increased efficacy of MET for distal ureteral stones
based on the meta-analyses published. The panel was aware
E U R O P E A N U R O L O G Y 7 1 ( 2 0 1 7 ) 5 0 4 – 5 0 7 505