Should we SUSPEND MET? Not really.

Abstract

Medical expulsive therapy (MET) in ureteric stones has 2 goals: 1) accelerate stone passage and therefore avoid surgery and 2) reduce analgesic requirement. In this setting, a RCT [1] done prior to the publication of the SUSPEND trial [2] is published in this issue of the CEJU, comparing the efficacy of tadalafil against tamsulosin in MET. It is regrettable that a placebo arm was not included in this trial. Nevertheless, even if one were to presume that tamsulosin is only as good as placebo, a robust case is made for the superiority of tadalafil – the mean stone size in this trial is 7 mm; all the stones were in the distal ureter; stone passage was confirmed with CT scan; the tadalafil group had a 84% passage rate compared to 68% in the tamsulosin group; mean analgesic requirement and time to stone expulsion were significantly reduced in the tadalafil group. Tamsulosin and nifedipine are supposed to be beneficial in MET, but high-quality RCTs in this area were lacking [3, 4]. PDE-5 inhibitors have been investigated as alternative agents in MET [5]. The SUSPEND trial concluded that there is no benefit to using tamsulosin or nifedipine in MET, compared to placebo. However, the conclusions were not supported by its methodology. Trials are scientifically rigorous pursuits; if diluted with ‘real-world’ or ‘pragmatic’ labels, they defeat the objective. The primary outcome to look into the effectiveness of MET is spontaneous passage of stone – confirmed, ideally, with CT scan or the patient submitting a stone that was passed per urethrem. Any other outcome measure is unlikely to yield the same result. The SUSPEND trial used lack of surgical intervention as a proxy for its primary outcome, citing radiation safety and costs for not using CT scans. The trial also suffers from other anomalies: ∼75% of the stones in each arm of the trial was ≤5 mm; only ∼65% of the stones were in the lower ureter; using maximal stone dimension rather than ureteral cross sectional dimension (attribution bias). The study from Bengaluru gives hope to patients and clinicians alike through the possibility of using agents other than tamsulosin and nifedipine in MET. Higher quality trials are required to establish the role of specific agents in MET, tailored to size and location of stones. In the absence of RCTs that are rigorous in their methodology, urologists are likely to continue prescribing agents for MET. One cannot help but be reminded of Yogi Berra's malapropism here: “You've got to be very careful if you don't know where you are going, because you might not get there”.