Comparative study of patient reported Outcomes, Cost and Stone free rates of ESWL and URSL for lower ureteric stones: A Randomized Control Trial

Urinary stone disease is very common with an estimated prevalence among the general population of 2–3%. Ureteric stones are associated with severe pain as they pass through the urinary tract and have significant impact on patients’ quality of life due to the detrimental effect on their ability to work and need for hospitalisation. Most ureteric stones can be expected to pass spontaneously with supportive care. However, between one-fifth and one-third of cases require an intervention. (1)

The two standard active intervention options are extracorporeal shockwave lithotripsy (ESWL) and ureteroscopic stone retrieval. ESWL and ureteroscopy are effective in terms of stone clearance; however, they differ in terms of invasiveness, anaesthetic requirement, treatment setting, complications, patient-reported outcomes (e.g. pain after intervention, time off work) and cost.(2) There is uncertainty around which is the most clinically effective in terms of stone clearance and the true cost to the patient and to society (in terms of impact on patient-reported health and economic burden).

The aim of this trial is to determine whether in adults with lower ureteric stones judged to require active treatment, ESWL is not inferior, clinically, and is  more cost-effective compared to ureteroscopic treatment as the initial management option. (3)

   REVIEW OF LITERATURE

 A joint clinical guideline on the management of ureteric stones by the European Association of Urology and the American Urological Association [4] estimates that 68% of stones ≤ 5 mm and 47% of stones 5–10 mm in size can be expected to pass spontaneously and concluded that the majority of these stones pass within four to six weeks of presentation. Stones in the distal ureter pass more readily than stones located more proximally. Consequently, patients with favourable features and with smaller sized stones in the lower ureter are initially treated conservatively. Immediate active intervention occurs in those patients with larger stones and unfavourable features who are deemed clinically to be unsuitable for conservative treatment. Those who fail standard conservative care or who subsequently develop complications also undergo later active treatment. This can be ESWL, preliminary ureteric stenting with later stone removal, ureteroscopy with stone retrieval or destruction (in situ lithotripsy) or percutaneous nephrostomy insertion and later stone removal. ESWL and ureteroscopic treatment require expensive equipment and urological expertise. Both have been shown to be options that are safe and effective in a number of studies. In clinical practice, urologists tend to favour ureteroscopy over ESWL particularly for mid and lower ureteric stones due to perceived higher rate of clinical stone clearance [5].

A Cochrane systematic review (2007) [5] comparing the effectiveness of ESWL with ureteroscopic management of ureteric stones identified seven randomised controlled trials (RCTs) involving a total of 732 participants. The results of this review suggest stone-free rates were lower in the ESWL group (RR (relative risk) = 0.83, 95% confidence interval [CI] = 0.70–0.98); reflecting this retreatment, rates for ESWL were higher (RR = 2.78, 95% CI = 0.53–14.71) but these findings are associated with much uncertainty. Complications were less frequent after ESWL (RR = 0.44, 95% CI = 0.21–0.92) and this option was associated with a shorter hospital stay (mean difference = 2.10 days, 95% CI = – 2.55 – – 1.64 days). The review concluded that ureteroscopic treatment of stones was associated with a higher stone free rate but a higher morbidity (complication rate) and a longer hospital stay. However, the overall quality of the studies was poor and inclusion criteria were strict in each study, limiting both the generalisability and applicability of the review findings. There was limited evidence on which to judge the comparative effectiveness in clinically important prognostic subgroups for example location of stones in the ureter. None of the studies reported on health-related quality of life and only one reported a cost-effectiveness outcome. The review authors recommended that a large-scale multicentre RCT was needed to adequately address the effectiveness and cost-effectiveness of ureteroscopy versus ESWL. A 2011 update of the Cochrane review [5] has included two further studies but these have not altered the previous conclusions.

The European Association of Urology and the American Urological Association (EAU-AUA) Clinical Guideline Panel on the management of ureteric stones also conducted a review and meta-analysis reporting clinical outcomes and complications following treatment of ureteric stones with ESWL or ureteroscopy, including data from non-randomised comparisons and case series [4]. Pre-defined outcome measures were stone-free rate and number of additional procedures required. The results were stratified according to stone location in the ureter (proximal, mid, distal) and stone diameter (≤ 10 mm,

 10 mm). All forms of ESWL were analysed as a single treatment modality in the meta-analysis. The Panel concluded that the main advantage of ureteroscopy is a higher stone-free rate with a single procedure, but with a higher complication rate. However, the evidence was insufficient for the Panel to recommend between ESWL and ureteroscopy and concluded that for patients requiring active stone removal, either treatment modality is acceptable as first-line options. For the individual patient, the choice is often determined by a number of factors including the availability of resources, preference of the treating urologist, and preference of the patient. The review highlighted design and reporting deficiencies from available studies, including poor definition of stone size, inconsistent reporting of outcomes and lack of randomisation. One of the main recommendations of the Panel was the need to conduct RCTs comparing the clinical and cost-effectiveness of ESWL and ureteroscopy.

The aim of this study is to determine whether in adults with ureteric stones judged to require active treatment, ESWL is not inferior, clinically, and is  more cost-effective compared to ureteroscopic treatment as the initial management option.

AIM

To assess feasibility and efficacy of ESWL for management of lower ureteric stones

PRIMARY OBJECTIVES

1. Stone free rates at 1 week, 8 weeks and 3 months post intervention in both groups
2. Acceptability and patient satisfaction of received procedure at eight weeks post enrollment.

 SECONDARY OBJECTIVES

1. Additional interventions required up to three months post primary intervention.
2. Complications observed in both groups up to three months post intervention.
3. Acceptability and patient satisfaction of received procedure at eight weeks post enrollment.
4. Loss of working days for the management of the lower ureteric calculus.
5. Pain intensity and analgesic requirement at pre intervention, during intervention, at one week post intervention and at eight weeks post enrollment.
6. Functional generic health and wellbeing (SF-12), at eight weeks and at three months post enrollment.

  MATERIALS AND METHODS

Study design**:** Randomized control trial

Time Duration**:** January 2023 to December 2024, 24 months

Venue of Study**:** Department of Urology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.

Study population**:** Patients with lower ureteric calculus attending Department of Urology, AIIMS, Jodhpur for management.

 PATIENT SELECTION:

INCLUSION CRITERIA

1.     Presence of lower ureteric stone confirmed by CT KUB

2.     Patients with a ureteric stone requiring active intervention

3.     Adults aged ≥ 18 years

4.     Suitable for either ESWL or ureteroscopic treatment

EXCLUSION CRITERIA:

1. Patients who are unable to provide consent

2.     Radiolucent stones

3.     Active urinary tract infections

4.     Pregnancy

5.     Uncontrolled hypertension

6.     Uncontrolled bleeding tendencies

7.     Severe skeletal malformations

8.     Vascular malformations within the vicinity of the stone (such as iliac artery aneurysms)

9.     Unable to assume the appropriate position (prone or supine) for ESWL

10.  Solitary kidneys

11.  Transplanted kidneys