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. TRIAL REGISTRATION: This trial is registered as ISRCTN92289221. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 19. See the NIHR Journals Library website for further project information.

Approximately 1 in 20 people suffers from kidney stones that pass down the urine drainage tube (ureter) into the urinary bladder and cause episodes of severe pain (ureteric colic). People with ureteric colic attend hospital for pain relief and diagnosis. Although most stones smaller than 10 mm eventually reach the bladder and are passed during urination, some get stuck and have to be removed using telescopic surgery (called ureteroscopic stone treatment) or shockwave therapy (called shockwave lithotripsy). Ureteroscopic stone treatment involves passing a telescope-containing instrument through the bladder and into the ureter to fragment and/or remove the stone. This is usually carried out under general anaesthetic as a day case. For shockwave lithotripsy, the patient lies flat on a couch and the apparatus underneath them generates shockwaves that pass through the skin to the ureter and break the stones into smaller fragments, which can be passed naturally in the urine. This involves using X-ray or ultrasound to locate the stone, but can be carried out on an outpatient basis and without general anaesthetic. Telescopic surgery is known to be more successful at removing stones after just one treatment, but it requires more time in hospital and has a higher risk of complications than shockwave lithotripsy (however, shockwave lithotripsy may require more than one session of treatment). Our study, the Therapeutic Interventions for Stones of the Ureter trial, was designed to establish if treatment for ureteric colic should start with telescopic surgery or shockwave therapy. Over 600 NHS patients took part and they were split into two groups. Each patient had an equal chance of their treatment starting with either telescopic surgery or shockwave lithotripsy, which was decided by a computer program (via random allocation). We counted how many patients in each group had further procedures to remove their stone. We found that telescopic surgery was 11% more effective overall, with an associated slightly better quality of life (10 more healthy days over the 6-month period), but was more expensive in an NHS setting. The finding of a lack of any significant additional clinical benefit leads to the conclusion that the more cost-effective treatment pathway is shockwave lithotripsy with telescopic surgery used only in those patients in whom shockwave lithotripsy is unsuccessful.

Standardising the Assessment of Patient-reported Outcome Measures in Localised Prostate Cancer. A Systematic Review.

CONTEXT: Prostate cancer (PCa) is the second most common cancer among men worldwide. Urinary, bowel, and sexual function, as well as hormonal symptoms and health-related quality of life (HRQoL), were prioritised by patients and professionals as part of a core outcome set for localised PCa regardless of treatment type. OBJECTIVE: To systematically review the measurement properties of patient-reported outcome measures (PROMs) used in localised PCa and recommend PROMs for use in routine practice and research settings. EVIDENCE ACQUISITION: The psychometric properties of PROMs measuring functional and HRQoL domains used in randomised controlled trials including patients with localised PCa were assessed according to the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) methodology. MEDLINE and Embase were searched to identify publications evaluating psychometric properties of the PROMs. The characteristics and methodological quality of the studies included were extracted, tabulated, and assessed according to the COSMIN criteria. EVIDENCE SYNTHESIS: Overall, 27 studies evaluating psychometric properties of the Expanded Prostate Cancer Index Composite (EPIC), University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), European Organisation for Research and Treatment of Cancer (EORTC) quality of life core 30 (QLQ-C30) and prostate cancer 25 (QLQ-PR25) modules, International Index of Erectile Function (IIEF), and the 36-item (SF-36) and 12-item Short-Form health survey (SF-12) PROMs were identified and included in the systematic review. EPIC and EORTC QLQ-C30, a general module that assesses patients' physical, psychological, and social functions, were characterised by high internal consistency (Cronbach's α 0.46-0.96 and 0.68-0.94 respectively) but low content validity. EORTC QLQ-PR25, which is primarily designed to assess PCa-specific HRQoL, had moderate content validity and internal consistency (Cronbach's α 0.39-0.87). UCLA-PCI was characterised by moderate content validity and high internal consistency (Cronbach's α 0.21-0.94). However, it does not directly assess hormonal symptoms, whereas EORTC QLQ-PR25 does. CONCLUSION: The tools with the best evidence for psychometric properties and feasibility for use in routine practice and research settings to assess PROMs in patients with localised PCa were EORTC QLQ-C30 and QLQ-PR25. Since EORTC QLQ-C30 is a general module that does not directly assess PCa-specific issues, it should be adopted in conjunction with the QLQ-PR25 module. PATIENT SUMMARY: We reviewed and appraised the measurement properties of patient-reported outcome measure questionnaires used for patients with localised prostate cancer. We found good evidence to suggest that two questionnaires (EORTC QLQ-C30 and QLQ-PR25) can be used to measure urinary, bowel, and sexual functions and health-related quality of life.