Shockwave lithotripsy compared with ureteroscopic stone treatment for adults with ureteric stones: the TISU non-inferiority RCT

BACKGROUND: Urinary stone disease affects 2-3% of the general population. Ureteric stones are associated with severe pain and can have a significant impact on a patient's quality of life. Most ureteric stones are expected to pass spontaneously with supportive care; however, between one-fifth and one-third of patients require an active intervention. The two standard interventions are shockwave lithotripsy and ureteroscopic stone treatment. Both treatments are effective, but they differ in terms of invasiveness, anaesthetic requirement, treatment setting, number of procedures, complications, patient-reported outcomes and cost. There is uncertainty around which is the more clinically effective and cost-effective treatment. OBJECTIVES: To determine if shockwave lithotripsy is clinically effective and cost-effective compared with ureteroscopic stone treatment in adults with ureteric stones who are judged to require active intervention. DESIGN: A pragmatic, multicentre, non-inferiority, randomised controlled trial of shockwave lithotripsy as a first-line treatment option compared with primary ureteroscopic stone treatment for ureteric stones. SETTING: Urology departments in 25 NHS hospitals in the UK. PARTICIPANTS: Adults aged ≥ 16 years presenting with a single ureteric stone in any segment of the ureter, confirmed by computerised tomography, who were able to undergo either shockwave lithotripsy or ureteroscopic stone treatment and to complete trial procedures. INTERVENTION: Eligible participants were randomised 1 : 1 to shockwave lithotripsy (up to two sessions) or ureteroscopic stone treatment. MAIN OUTCOME MEASURES: The primary clinical outcome measure was resolution of the stone episode (stone clearance), which was operationally defined as 'no further intervention required to facilitate stone clearance' up to 6 months from randomisation. This was determined from 8-week and 6-month case report forms and any additional hospital visit case report form that was completed by research staff. The primary economic outcome measure was the incremental cost per quality-adjusted life-year gained at 6 months from randomisation. We estimated costs from NHS resources and calculated quality-adjusted life-years from participant completion of the EuroQol-5 Dimensions, three-level version, at baseline, pre intervention, 1 week post intervention and 8 weeks and 6 months post randomisation. RESULTS: In the shockwave lithotripsy arm, 67 out of 302 (22.2%) participants needed further treatment. In the ureteroscopic stone treatment arm, 31 out of 302 (10.3%) participants needed further treatment. The absolute risk difference was 11.4% (95% confidence interval 5.0% to 17.8%); the upper bound of the 95% confidence interval ruled out the prespecified margin of non-inferiority (which was 20%). The mean quality-adjusted life-year difference (shockwave lithotripsy vs. ureteroscopic stone treatment) was -0.021 (95% confidence interval 0.033 to -0.010) and the mean cost difference was -£809 (95% confidence interval -£1061 to -£551). The probability that shockwave lithotripsy is cost-effective is 79% at a threshold of society's willingness to pay for a quality-adjusted life-year of £30,000. The CEAC is derived from the joint distribution of incremental costs and incremental effects. Most of the results fall in the south-west quadrant of the cost effectiveness plane as SWL always costs less but is less effective. LIMITATIONS: A limitation of the trial was low return and completion rates of patient questionnaires. The study was initially powered for 500 patients in each arm; however, the total number of patients recruited was only 307 and 306 patients in the ureteroscopic stone treatment and shockwave lithotripsy arms, respectively. CONCLUSIONS: Patients receiving shockwave lithotripsy needed more further interventions than those receiving primary ureteroscopic retrieval, although the overall costs for those receiving the shockwave treatment were lower. The absolute risk difference between the two clinical pathways (11.4%) was lower than expected and at a level that is acceptable to clinicians and patients. The shockwave lithotripsy pathway is more cost-effective in an NHS setting, but results in lower quality of life. FUTURE WORK: (1) The generic health-related quality-of-life tools used in this study do not fully capture the impact of the various treatment pathways on patients. A condition-specific health-related quality-of-life tool should be developed. (2) Reporting of ureteric stone trials would benefit from agreement on a core outcome set that would ensure that future trials are easier to compare.