Shockwave Lithotripsy Versus Ureteroscopic Treatment as Therapeutic Interventions for Stones of the Ureter (TISU): A Multicentre Randomised Controlled Non-inferiority Trial

Abstract

Background: Renal stone disease is common and can cause emergency presentation with acute pain due to ureteric colic. International guidelines have stated the need for a multicentre randomised controlled trial (RCT) to determine whether a non-invasive outpatient (shockwave lithotripsy [SWL]) or surgical (ureteroscopy [URS]) intervention should be the first-line treatment for those needing active intervention. This has implications for shaping clinical pathways.

Objective: To report a pragmatic multicentre non-inferiority RCT comparing SWL with URS.

Design, setting, and participants: This trial tested for non-inferiority of up to two sessions of SWL compared with URS as initial treatment for ureteric stones requiring intervention.

Outcome measurements and statistical analysis: The primary outcome was whether further intervention was required to clear the stone, and secondary outcomes included quality of life assessment, severity of pain, and serious complications; these were based on questionnaires at baseline, 8 wk, and 6 mo. We included patients over 16 yr with a single ureteric stone clinically deemed to require intervention. Intention-to-treat and per-protocol analyses were planned.

Results and limitations: The study recruited between July 1, 2013 and June 30, 2017. We recruited 613 participants from a total of 1291 eligible patients, randomising 306 to SWL and 307 to URS. Sixty-seven patients (22.1%) in the SWL arm needed further treatment compared with 31 patients (10.3%) in the URS arm. The absolute risk difference was 11.7% (95% confidence interval 5.6%, 17.8%) in favour of URS, which was inside the 20% threshold we set for demonstrating noninferiority of SWL.

Conclusions: This RCT was designed to test whether SWL is non-inferior to URS and confirmed this; although SWL is an outpatient noninvasive treatment with potential advantages both for patients and for reducing the use of inpatient health care resources, the trial showed a benefit in overall clinical outcomes with URS compared with SWL, reflecting contemporary practice. The Therapeutic Interventions for Stones of the Ureter (TISU) study provides new evidence to help guide the choice of modality for this common health condition.

Patient summary: We present the largest trial comparing ureteroscopy versus extracorporeal shockwave lithotripsy for ureteric stones. While ureteroscopy had marginally improved outcome in terms of stone clearance, as expected, shockwave lithotripsy had better results in terms of health care costs. These results should enable patients and health care providers to optimise treatment pathways for this common urological condition.

Keywords: Extracorporeal shockwave lithotripsy; Randomised controlled trial; Therapeutic interventions for symptomatic ureteric stones; Trial; Ureteric stones; Ureteroscopy.

Fig. 1

Consort diagram. SWL = shockwave lithotripsy; URS = ureteroscopy. ^a Eighty-six patients had two sessions of SWL. ^b SWL arm: other = stone passed before treatment (n = 52) and not treated within the NHS/did not attend/unable to treat (n = 4); URS arm: other = stone passed before treatment (n = 36), and not treated within the NHS/did not attend/unable to treat (n = 8). ^c Three had two sessions of SWL.

Fig. 2

Plots over time of complete case quality of life data using EQ-5D-3L (mean score and VAS) and the SF-12 physical (PCS) and mental (MCS) component scores. EQ-5D-3L is a complex composite of five questions scoring 0–2, where 0 represents “no problem”. Ultimately, these are combined such that the maximum score is 1, indicating the best health state, using the UK value set. EQ-5D VAS is a visual analogue scale ranging from 0 to 100, whereby 100 indicates the best health status. SF-12v2: Physical and mental health composite scores (PCS and MCS) are scores from 12 questions ranging from 0 to 100; for each scale, 0 indicates the lowest level of health measured and 100 indicates the highest level of health. SF-12 = Short Form-12; SWL = shockwave lithotripsy; URS = ureteroscopy; VAS = visual analogue scale.