Wiseman O. et al., 2025: Clinical and cost-effectiveness of percutaneous nephrolithotomy, flexible ureterorenoscopy and extracorporeal shockwave lithotripsy for lower pole stones: the PUrE RCTs.

Oliver Wiseman, Daron Smith, Kath Starr, Lorna Aucott, Rodolfo Hernández, Ruth Thomas, Steven MacLennan, Charles Terry Clark, Graeme MacLennan, Dawn McRae, Victoria Bell, Seonaidh Cotton, Zara Gall, Ben Turney, Samuel McClinton
Health Technol Assess. 2025 Aug;29(40):1-186. doi: 10.3310/WFRE6844 FREE FULL TEXT

Abstract

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
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. 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. 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.

Comment Peter Alken

A Must Read!
This is one of my Reviewers Choice only by just looking at the abstract! This is a 186 pages document. It is a surprise to see that such a disruptive study is coming from Great Britain with its much-condemned NHS system.
Here are some details from the text of the document to better understand HTA programme and the origin of the present studies:
“This article presents independent research funded by the National Institute for Health and Care Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, the HTA programme or the Department of Health and Social Care”
“Health Technology Assessment (HTA) research is undertaken where some evidence already exists to show that a technology can be effective and this needs to be compared to the current standard intervention to see which works best. Research can evaluate any intervention used in the treatment, prevention or diagnosis of disease, provided the study outcomes lead to findings that have the potential to be of direct benefit to NHS patients.”

Peter Alken