Clinical and cost-effectiveness of percutaneous nephrolithotomy, flexible ureterorenoscopy and extracorporeal shockwave lithotripsy for lower pole stones: the PUrE RCTs
Background Renal tract stone disease is common. The three intervention options are shockwave lithotripsy, flexible ureteroscopic stone treatment and keyhole surgery. Objectives To determine which of shockwave lithotripsy, flexible ureteroscopic stone treatment and keyhole surgery offer the best outc...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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NIHR Journals Library
2025-08-01
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| Series: | Health Technology Assessment |
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| Online Access: | https://doi.org/10.3310/WFRE6844 |
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| Summary: | Background Renal tract stone disease is common. The three intervention options are shockwave lithotripsy, flexible ureteroscopic stone treatment and keyhole surgery. Objectives To determine which of shockwave lithotripsy, flexible ureteroscopic stone treatment and keyhole surgery offer the best outcomes in terms of health and quality of life, clinical effectiveness and cost-effectiveness for people with lower pole kidney stones. Design The PUrE study comprised two pragmatic multicentre, open-label, superiority randomised controlled trials: RCT1 for lower pole stones ≤ 10 mm and RCT2 for lower pole stones > 10 and ≤ 25 mm. Setting National Health Service Urology departments. Participants Adults presenting with lower pole renal stones, able to undergo any of the treatments and complete trial procedures. Intervention Eligible participants were randomised in RCT1 to flexible ureteroscopic stone treatment or shockwave lithotripsy; and in RCT2 to flexible ureteroscopic stone treatment or keyhole surgery. Main outcome measures The primary outcome measure was health status ‘area under the curve’, measured weekly to 12 weeks post intervention with the EuroQol-5 Dimensions, five-level version. The primary economic outcome was the incremental cost per quality-adjusted life-year gained at 12 months from randomisation. Results RCT1: A total of 461 participants were randomised: 231 to flexible ureteroscopic stone treatment; and 230 to shockwave lithotripsy. RCT2: A total of 159 participants were randomised: 73 to flexible ureteroscopic stone treatment; and 86 to keyhole surgery. Primary outcome RCT1: The mean health status area under the curve was 0.807 (standard deviation 0.205) in the flexible ureteroscopic stone treatment group (n = 164) and 0.826 (standard deviation 0.207) in the shockwave lithotripsy group (n = 188). The between-group difference, 0.024 (95% confidence interval −0.004 to 0.053), was a small difference in favour of flexible ureteroscopic stone treatment after correcting for a baseline imbalance. Complete stone clearance was higher with flexible ureteroscopic stone treatment (72%) than shockwave lithotripsy (36%). RCT2: The mean health status area under the curve was 0.794 (standard deviation 0.198) in the flexible ureteroscopic stone treatment group (n = 57) and 0.818 (standard deviation 0.217) in the keyhole surgery group (n = 63). The between-group difference, −0.07 (95% confidence interval −0.11 to −0.02), was a borderline meaningful difference favouring keyhole surgery. Complete stone clearance was higher with keyhole surgery (71%) than flexible ureteroscopic stone treatment (48%). Economic evaluation RCT1: Flexible ureteroscopic stone treatment is more costly (£1138; 95% confidence interval £646 to £1631) and produces 0.017 (95% confidence interval −0.008 to 0.043) additional quality-adjusted life-years; with an incremental cost-effectiveness ratio of £65,163 per quality-adjusted life-year gained. Shockwave lithotripsy has a 99.9% chance of being cost-effective at a £20,000 threshold value. RCT2: Flexible ureteroscopic stone treatment is more costly (£733; 95% confidence interval −£508 to £1973) and produces fewer quality-adjusted life-years (−0.001; 95% confidence interval −0.044 to 0.042). Keyhole surgery has an 87% chance of being cost-effective at a £20,000 threshold value. Limitations Blinding of participants and healthcare providers was not possible. There were differential waiting times between interventions in RCT1; however, adjusting for this gave similar treatment effect estimates. Conclusions The PUrE study found in RCT1 that shockwave lithotripsy was more cost-effective than flexible ureteroscopic stone treatment, with no meaningful difference in patient health status even though complete stone-free rates were higher with flexible ureteroscopic stone treatment. In RCT2, keyhole surgery was more cost-effective than flexible ureteroscopic stone treatment on a micro-costing basis, which better reflects treatment cost differences to the NHS. Keyhole surgery was marginally beneficial for health status with higher complete stone-free rates. Future work What effect will suction devices, improvements in laser technology, and intraoperative pressure monitoring have on postoperative pain, quality of life, stone-free rates, complications, and costs of flexible ureteroscopic stone treatment? What effect does miniaturisation of keyhole surgery have on postoperative pain, length of stay, complications, stone-free rates and costs? Trial registration This trial is registered as ISRCTN98970319. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/152/02) and is published in full in Health Technology Assessment; Vol. 29, No. 40. See the NIHR Funding and Awards website for further award information.
Plain language summary About 10% of people will suffer from kidney stones in their lifetime. Approximately 50% of those people will experience symptoms, typically kidney pain, and about 25% of patients with stones will require active treatment. Active treatments include shockwave therapy, telescopic surgery and keyhole surgery. Stones commonly develop in the lower part (pole) of the kidney. Previous studies suggested that for lower pole stones: and stones smaller than 10 mm in size, telescopic surgery is more likely to remove the stone with a single treatment and for larger stones, which are > 10 mm but smaller than 25 mm, keyhole surgery is more likely to remove the stone with a single treatment. Remarkably little evidence was available on the impact of these treatments on quality of life for patients. What did PUrE do? We assessed the effect on the participants’ health, and the economic impact to the National Health Service, of the different care pathways by conducting 2 studies involving over 600 patients with lower pole stones. The first study (smaller stones) compared telescopic surgery with shockwave therapy. The second study (larger stones) compared telescopic surgery with keyhole surgery. A computer program (random allocation) decided which treatment each person received. The patients, and the doctors caring for them, proceeded with the agreed treatment. All patients were requested to fill in quality-of-life questionnaires on a regular basis. What did PUrE find? We found that for shockwave therapy and keyhole surgery, improvement in participants’ health status was similar to telescopic surgery. Telescopic surgery was less cost-effective for the National Health Service in both studies. What does this mean? These studies show that, based on cost and health status, shockwave therapy and keyhole surgery are the first choice for active treatment in the National Health Service.
Scientific summary Background Renal tract stone disease is very common, with a lifetime prevalence of approximately 10% across the world. It mainly affects adults of working age, and the incidence has been increasing over recent decades. Approximately 50% of people with renal tract stones will experience symptoms, typically kidney pain, and about 25% of patients with stones will require active treatment. Many of these stones occur in the lower pole of the kidney and the three standard active intervention options are extracorporeal shockwave lithotripsy (ESWL), flexible ureteroscopic stone treatment (FURS) and keyhole surgery [percutaneous nephrolithotomy (PCNL)]. Objectives The aim of the PUrE study was to determine which of ESWL, FURS and PCNL offer the best treatment outcomes in terms of health status, clinical-effectiveness, and cost-effectiveness for people with lower pole kidney stones seeking treatment within the UK NHS. Methods Design Two pragmatic multicentre, patient-randomised, open-label superiority randomised controlled trials (RCTs): the first (RCT1) for lower pole stones (LPSs) ≤ 10 mm in maximum dimension and the second (RCT2) for LPSs > 10 and ≤ 25 mm. Setting National Health Service secondary care units across the UK, with a high volume of patients presenting with LPSs, and able to deliver all active treatments. Participants Adults (16 years or over) with lower pole renal stones judged to require active treatment. Intervention Treatment following either the ESWL, FURS or PCNL pathways. Participants that were eligible and consented were randomised within RCT1 to FURS or ESWL, or within RCT2 to FURS or PCNL. Main outcome measures Clinical: (1) Health status area under the curve (AUC) measured weekly to 12 weeks post intervention using the EuroQol-5 Dimensions, five-level version (EQ-5D-5L) and (2) stone clearance at 12 weeks. Economic: Incremental cost per quality-adjusted life-years (QALYs) gained at 12-months from randomisation. QALYs are based on the responses to the EQ-5D-5L. Results Main outcome RCT1: The mean health status AUC was 0.807 [standard deviation (SD) 0.205] in the FURS group (n = 164) and 0.826 (SD 0.207) in the ESWL group (n = 188). The adjusted effect estimate was 0.024 [confidence interval (CI) −0.004 to 0.053] and this was not significant (p = 0.097). Complete stone clearance was higher with FURS (72%) than with ESWL (36%). RCT2: The mean health status AUC was 0.794 (SD 0.198) in the FURS group (n = 57) and was 0.818 (SD 0.217) in the PCNL group (n = 63). The adjusted effect estimate was −0.07 (CI −0.11 to −0.02; p = 0.006). Complete stone clearance was higher with PCNL (71%) than with FURS (48%). Economic evaluation RCT1: The mean cost for the NHS were £3362 and £2223 for the intention to treat (ITT) with FURS and ESWL groups, respectively, resulting in an adjusted cost difference of £1138 [95% confidence interval (CI) £646 to £1631]. The mean QALYs per participant were 0.804 and 0.787 for the FURS and ESWL groups, respectively, producing an adjusted QALY difference of 0.017 QALYs (95% CI −0.008 to 0.043) for the 12-month follow-up period. The incremental cost-effectiveness ratio (ICER) between FURS and ESWL was £65,163 per QALY gained by FURS. At a threshold value of £20,000 per QALY, ESWL has a 99.9% chance of being cost-effective. RCT2: The mean cost for the NHS was £5298 and £4565 for the ITT with FURS and PCNL, respectively; giving an adjusted difference of £733 (95% CI −£508 to £1973). The mean QALY per participant were 0.773 and 0.775 for FURS and PCNL, respectively, yielding an adjusted difference of −0.001 (95% CI −0.044 to 0.042). Therefore, ITT with FURS is on average more costly and does not produce additional QALYs compared with ITT with PCNL. PCNL is highly likely to be cost-effective at the usual cost-effectiveness threshold values used for decision-making in the UK NHS (e.g. probability of 0.87 at £20,000 per QALY gained). These results, however, are dependent on the method used to estimate the costs of the initial interventions. Therefore, using costings based on the Health Care Resource Group (HRG) the mean cost for the NHS was £5769 for FURS and £6703 for PCNL; resulting in FURS being £934 less costly than PCNL (95% CI −£2582 to £714: ICER: £883,375). That is, ITT with FURS would save on average, £883,375 per QALY forgone. Comparison with similar randomised trials The health status outcomes and the economic outcomes, as they relate to the UK NHS, have not been evaluated in previous randomised trials. Conclusions The PUrE study shows in RCT1 that ESWL for lower renal pole stones under 10 mm was more cost-effective than FURS, and there was no meaningful difference in patient health status. Stone-free rates (SFRs) were higher, however with FURS. From an overall NHS perspective, the costs savings of treating all patients with these stones with ESWL would be substantial. In RCT2, for larger stones 10–25 mm, PCNL was more cost-effective than FURS when using micro-costing to cost the interventions. Health status was marginally beneficial and SFRs were higher with PCNL. Implications for health care The choice of health status assessment as the primary outcome measure provides important data for patient counselling for decision-making and for resource allocation based on the cost per QALY analysis. RCT1 demonstrated that ESWL was the more cost-effective treatment for LPSs < 10 mm. This complements the recommendation from National Institute for Health and Care Excellence (NICE) Renal Stone Guidelines 2019 that ESWL should be offered as the first-line intervention for renal stones of this size. In RCT2 the cost-effectiveness for FURS and PCNL is less clear-cut, because of the discrepancy between a micro-costing analysis (which showed PCNL was more cost-effective) and HRG-based analysis (which showed that FURS was more cost-effective). It is unclear to us why the HRG costs differ that much between FURS and PCNL given the resources used do not substantially differ between the two procedures. Greater transparency in the way the HRG are costed would be beneficial to inform decision-making in the NHS. The consistent drop in health status at week one in both trials, particularly for those in the FURS treatment arms has important implications for practice during consent to treatment. Based on this data it is important for clinicians to emphasise that patients are likely to feel worse before they feel better. While this is true of most surgical interventions, and therefore likely to be expected by most patients, the PUrE study provides detailed information regarding the anticipated post-treatment health status that will help make patients’ consent to be more fully informed. The results from RCT1 show no meaningful difference in health status, while RCT2 indicates marginal benefit for PCNL. However, when considering secondary outcomes, patients should be counselled that for smaller LPSs < 10 mm, FURS leads to a higher stone free rate than ESWL, and for LPSs between 10 and 25 mm, PCNL leads to higher stone free rates than FURS. Recommendations for research What effect will suction devices, improvements in laser technology, and intraoperative pressure monitoring have on postoperative pain, QoL, SFRs, complications, and costs of FURS? What is the effect of minaturisation of PCNL on postoperative pain, length of stay, complications, SFRs, and costs? What is the clinical and cost-effectiveness of full metabolic assessment compared with standard advice alone, in people who have undergone treatment for LPSs? Trial registration This trial is registered as ISRCTN98970319. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/152/02) and is published in full in Health Technology Assessment; Vol. 29, No. 40. See the NIHR Funding and Awards website for further award information. |
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| ISSN: | 2046-4924 |