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Cochrane Database of Systematic Reviews Protocol - Intervention

Percutaneous nephrolithotomy versus retrograde intrarenal surgery for treatment of renal stones in adults

Authors' declarations of interest

Version published: 07 October 2019 Version history

https://doi.org/10.1002/14651858.CD013445

This is not the most recent version

view the current version 13 November 2023
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Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To assess the effects of percutaneous nephrolithotomy versus retrograde intrarenal surgery for treatment of renal stones in adults.

Background

Description of the condition

Urolithiasis refers to the development of stones in the urinary tract. It is a common condition, with an increasing global incidence and prevalence across sex, race, and age groups (Romero 2010). Epidemiological studies indicate an 8.8% lifetime risk for stone disease in the US population (10.6% in men, 7.1% in women), an increase from 5.2% lifetime risk from 1988 to 1994 (Scales 2012; Sorokin 2017). Similar increases in prevalence have been noted in multiple countries across North America, Europe, and Asia (Romero 2010; Rukin 2017). Although small stones and larger intrarenal stones may be relatively asymptomatic, obstructive stones can cause severe abdominal and flank pain, nausea, vomiting, fever, and urinary symptoms. Additional complications resulting from stone disease include hydronephrosis and impaired renal function, as well as an increased lifetime risk for chronic kidney disease (Rule 2011). Furthermore, the cost for management of stone disease is high, with estimated costs of several billion dollars per year in the US alone (Canvasser 2017; Saigal 2005).

Current recommendations from the American Urological Association (AUA) and European Association of Urology (EAU) for management of stones are primarily based on symptoms, stone location, and total stone burden. Ureteral stones can be treated medically or surgically. Both the AUA and EAU guidelines recommend observation for people with asymptomatic, non‐obstructing caliceal stones (Assimos 2016a; Assimos 2016b; Turk 2016). Smaller stones may pass spontaneously, particularly when located in the distal ureter or bladder, but ureteral stones that do not pass after four to six weeks may require surgical management, as the likelihood of spontaneous passage decreases significantly beyond this timeframe and prolonged retention of stones increases risk for renal injury (Miller 1999; Vaughan 1971). There is currently conflicting systematic review evidence regarding the use of medical expulsive therapy to aid passage of ureteral and renal stones less than 10 mm in diameter, however pharmacologic therapy may be a helpful for some people with symptomatic small stones (Assimos 2016a; Assimos 2016b; Campschroer 2018; Meltzer 2018; Pickard 2015; Turk 2016; Veser 2018). For larger ureteral stones or those located in the proximal ureter or higher, surgical management with ureteroscopy (URS) or shockwave lithotripsy (SWL) may be recommended (Assimos 2016a; Assimos 2016b; Turk 2016).

Asymptomatic, non‐obstructing renal stones can also be managed with observation, although the likelihood for spontaneous passage of a stone located in the proximal urinary tract is notably less than for those located in the distal ureters. Treatment decision‐making for symptomatic stones is highly dependent on location and total stone burden as indicated by diagnostic imaging. The imaging modality most commonly considered to provide best visualization of these characteristics is computed tomography (CT) scan, although abdominal films of the kidney, ureter, and bladder (KUB) are also commonly used. In particular, special consideration is given to stones located in the lower pole, due to the decreased possibility for fragmentation in this area (Danuser 2007; Pearle 2005; Sahinkanat 2008; Zumstein 2018). For people with non‐lower pole renal stones and a stone burden of 20 mm or less, first‐line therapy options include SWL or URS (Assimos 2016a; Assimos 2016b; Turk 2016). People with symptoms of lower pole renal stones and a total stone burden of 10 mm or less may be offered SWL or URS. For people with a total stone burden greater than 20 mm, percutaneous nephrolithotomy (PCNL) is currently recommended as first‐line therapy regardless of intrarenal stone location (Assimos 2016a; Assimos 2016b; Turk 2016).

Description of the intervention

Percutaneous nephrolithotomy

PCNL typically utilizes a 24‐Fr to 30‐Fr access sheath and was initially described in the literature by Fernström and Johansson in 1976 (Fernström 1976). In the decades following, it has become a widely used and well‐established treatment modality for the management of renal stones greater than 20 mm in diameter. Although it results in higher stone‐free rates than URS and SWL and is considered first‐line therapy for symptomatic adults with large total renal stone burden, standard PCNL is an invasive procedure with notable risk for complications and post procedure morbidity (Assimos 2016a; Assimos 2016b). The most common post procedure complications include bleeding (8%), need for blood transfusion (3% to 6%), and postoperative sepsis (2%) (Armitage 2012; Valdivia 2011). Risk for minor complications (Clavien‐Dindo Grade 1 to 2) and major complications (Clavien‐Dindo Grade 3 or higher) have been estimated.

Technological advancements in recent years have led to the miniaturization of PCNL access sheaths and instrumentation in order to decrease invasiveness and risks associated with the procedure, particularly significant bleeding and need for blood transfusion. Mini‐percutaneous nephrolithotomy (mini‐PCNL) utilizes an 11‐Fr to 24‐Fr access sheath and was first described as a technique used for children in 1998 (Jackman 1998). It has since been successfully adopted for treatment of renal stones in adults. Further advancements include the development of the 4.85‐Fr micro‐PCNL in 2011, ultra‐mini‐PCNL (11‐Fr to 13‐Fr) and mini‐micro‐PCNL (8‐Fr) in 2013, super‐mini‐PCNL in 2016, and numerous other small‐caliber approaches over the last decade for treatment of smaller stones (less than 20 mm diameter) (Desai 2012; Desai 2013; Jackman 1998; Li 2009; Nagele 2007; Sabnis 2013; Wright 2016; Zeng 2016). In addition to expanding the use of PCNL beyond its well‐documented use for large stone management, these small access sheath PCNLs provide additional options for stone management, for easier access to calculi in challenging locations such as the lower pole, as well as easier removal of stones that are impacted or embedded in calyceal diverticula (Wright 2016; Zeng 2018). Despite proposed advantages, such as decreased bleeding and shorter hospital stays, there is currently a dearth of literature evaluating whether small‐caliber PCNL procedures result in comparable stone clearance rates for large stones (greater than 20 mm) and have fewer risks for complications than with standard PCNL (Mishra 2011). The utility of small access sheath PCNL as a comparable alternative to or replacement for URS in the treatment of small stones (less than 20 mm) also remains poorly defined in the current urologic literature.

Imaging of the affected kidney, most commonly with abdominal CT scan, is obtained prior to PCNL and used as a guide for planning the procedure (Ko 2008; Marcovich 2005; Park 2006). Additional work‐up prior to the procedure includes urinalysis with possible follow‐up urine culture if urinary tract infection requiring preoperative treatment is suspected. People receiving anticoagulation should discontinue these medications prior to the procedure.

PCNL is most commonly performed under general anesthesia, and all patients receive broad‐spectrum antibiotics during the procedure to decrease the risk for infection (Ko 2008; Mariappan 2006). An open‐ended ureteric catheter is initially positioned in the renal pelvis with flex cystoscopy and fluoroscopic guidance (Ko 2008; Marcovich 2005). Access to the affected calyx is obtained with ultrasound or fluoroscopy‐guided needle puncture through the skin on the posterior flank and subsequently through the renal parenchyma and into the fornix of the affected renal calyx. A guidewire is passed through the lumen of the needle and into the renal collecting system, followed by tract dilation and placement of an access sheath. A nephroscope can then be placed through the sheath to directly visualize stones in the calyx, and any identified calculi are then fragmented using ultrasonic, mechanical, or laser lithotripsy. For smaller stones, the stone fragments are cleared using irrigation and stone graspers. Although a tubeless PCNL is possible, which refers to the omission of a postoperative nephrostomy tube, most procedures end with the placement of a nephrostomy tube after stone fragment removal (Kim 2003; Ko 2008).

Non‐contrast CT or nephrostogram are used one to two days postoperatively to assess stone clearance (Ko 2008). The nephrostomy tube can be removed at this time in people determined to be free of remaining large stone fragments; however, it may be necessary to perform a second nephroscopy to further fragment and clear retained calculi for people with retained stone fragments.

Retrograde intrarenal surgery

Retrograde intrarenal surgery (RIRS) via flex ureteroscopy (fURS) was initially described in the literature in 1964 (Marshall 1964). It is primarily indicated for management of renal calculi 10 mm to 20 mm in diameter, however its use has expanded in recent years to include larger stones (greater than 20 mm) that were previously only managed with PCNL (Sanguedolce 2017; Van Cleynenbreugel 2017). The most common complications associated with the procedure include bleeding and potential need for blood transfusion, ureteral injury (including mucosal injury, perforation, and stricture formation), stone impaction and migration, fever, infection (both local urinary tract infection and sepsis), pain, and postoperative urinary retention (Somani 2017).

RIRS is commonly performed under general anesthesia, but can also be done with combined spinal and epidural anesthesia (Van Cleynenbreugel 2017; Zeng 2015). Preoperative antibiotic prophylaxis is recommended for all patients undergoing URS, per current AUA guidelines (Assimos 2016a; Assimos 2016b). Preoperative stents can be placed prior to RIRS for people who have UTIs, limited renal function, ureteral abnormalities that limit ureteroscopic access, and in emergency settings (Van Cleynenbreugel 2017). For the procedure, patients are placed in the dorsal lithotomy position and under fluoroscopic guidance, a guidewire and safety wire are threaded into the renal collecting system and a ureteral access sheath may be placed based on surgeon preference. A flex ureteroscope is then advanced through the sheath to visualize the bladder, ureters, and renal pelvis and identify stones requiring fragmentation. If a ureteral access sheath is used, then the bladder and urethra are bypassed and thus, not visualized. Laser lithotripsy or mechanical fragmentation can then be performed. Laser fragmentation is completed using a Holmium‐YAG laser fiber with settings for pulse frequency and energy based on surgeon choice and preferred techniques, such as dusting (low joules, high frequency) or planned stone fragmentation with individual stone fragment basket retrieval (high joules, low frequency). Following fragmentation, larger stone fragments (greater than 1 mm) can be removed via basket retrieval and residual stone dust can be flushed out with irrigation. Finally, RIRS may involve the placement of a double‐J stent at the completion of the procedure to further aid stone fragment passage and prevent hydronephrosis, pain, and formation of ureteral strictures. DJ stents are generally left for three to 10 days postoperatively and removed in an outpatient setting (Van Cleynenbreugel 2017).

Adverse effects of the interventions

Risks and adverse outcomes associated with PCNL include postoperative pain, infection (including risk for sepsis), hemorrhage (including potential need for blood transfusion), renal collecting system injury or obstruction (or both), injury to surrounding organs (including colon, spleen, liver, and diaphragm and associated pleura), renal dysfunction, extravasation/urine leak, and mortality (Ko 2008; Kondas 1994; Marcovich 2005; Roth 1988; Wolf 1998; Wright 2016).

Risks and adverse outcomes associated with RIRS include postoperative pain, fever, infection (including risk for urosepsis), mucosal or ureteric injury, stone migration, hematuria (4.2%), renal collecting system injury or obstruction (including risk for ureteral avulsion or stricture) (or both), injury to surrounding organs, renal dysfunction, extravasation/urine leak, persistent vesicoureteral reflux, and mortality (de la Rosette 2014; Geavlete 2006; Somani 2017; Wright 2014). Placement of a ureteral stent can also result in increased postoperative pain for some patients (Ordonez 2019). Stent‐related symptoms are experienced by up to 80% of patients following placement (Joshi 2003).

How the intervention might work

PCNL and RIRS are performed on people with confirmed kidney stones. For PCNL, access to the stones is obtained via a percutaneous nephrostomy tube placed into the flank of a patient, through the outer renal cortex, and into the renal pelvis. Through this portal, instruments can be passed into the kidney, where they can be used to fragment large stones with energy, laser, or mechanical force. Once fragmented, the tube can be used for basketing devices that can hold and physically extract small whole stones and stone fragments. It also can be used for irrigation to flush out smaller particles following fragmentation. After the procedure, a smaller tube is placed at the surgical site and sewn to the skin. This tube allows drainage of urine, maintained patency of the access tract in the event that a second look is anticipated, and purported tamponade of the tract to decrease risk of hemorrhage. Imaging is used to confirm the successful removal of renal stones, and following this confirmation, the drainage tube can be removed.

For RIRS, access to stones is obtained via a flexible or semi‐rigid ureteroscope passed through the urethra, bladder, and ureter in order to reach the renal pelvis. A camera within the URS allows for visualization of stones that are present, and a portal in the scope allows for passage of instruments for fragmentation of stones. Similar to PCNL, stones can be fragmented using energy, laser, or mechanical force. After fragmentation, irrigation is used to flush out smaller stone particles, and a basket may be used to retrieve larger fragments. A ureteral stent may be placed at the procedure's conclusion in order to facilitate passage of stone fragments. Imaging is used to confirm the successful removal of the renal stones, and following this confirmation, the stent can be removed. This stent can remain in place for up to two weeks, and removal can take placed via outpatient cystoscopy or via traction placed on a string attached to the stent and visualized at the external urethra.

Why it is important to do this review

With technological advancements in endourology, PCNL has become feasible through smaller access tracts and with lower risk for morbidity. Although guideline recommendations for PCNL have previously been limited to larger renal stones, the utility of PCNL has expanded with the development of these smaller access tracts and less invasive procedure protocols. Meanwhile, ureteroscopic technology has also improved, thereby permitting the effective management of larger stones using a retrograde approach and expanding the indications for which URS may be an acceptable therapy. This is an extension of URS's application as indicated by recent guidelines for management of renal stones(Assimos 2016a; Assimos 2016b; Turk 2016). Overall, the expansion of both technologies makes the question of whether to employ PCNL or RIRS for definitive stone management less clear, even when taking into account stone size and location and risk for adverse effects associated with each approach.

Existing systematic reviews provide conflicting evidence about the effectiveness of PCNL and RIRS for stone clearance with regards to renal stone size and location, as well as the risk for adverse outcomes associated with each approach when employed for renal stone extraction e (De 2015; Donaldson 2015; Gao 2017; Ghani 2016; Jiang 2017; Li 2018). Existing systematic reviews also have not applied the same methodological rigor as a Cochrane Review. These include a focus on patient‐important outcomes; an a priori, published protocol; a comprehensive search that includes published and unpublished studies; and use of the GRADE approach with 'Summary of findings' tables (Guyatt 2008). We expect the findings of this review to provide important information to guideline clinicians and their patients, guideline developers, and policymakers with regard to the preferred management approach.

Objectives

To assess the effects of percutaneous nephrolithotomy versus retrograde intrarenal surgery for treatment of renal stones in adults.

Methods

Criteria for considering studies for this review

Types of studies

We will only include randomized controlled trials. We will exclude single‐arm studies or studies without an identified control.

We will include studies regardless of their publication status or language of publication.

Types of participants

We will include participants over 18 years of age who underwent PCNL or RIRS for clearance of renal stones.

We will exclude studies concerned with children, pregnant women, people with ureteric or bladder stones, people undergoing bilateral renal stone procedures, people with a solitary kidney, people with other anatomic renal abnormalities (congenital renal malformations such as horseshoe kidney, polycystic kidney disease, etc.), people with renal transplant, or people with systemic signs of infection at the time of procedure.

Should we identify studies in which only a subset of participants are relevant to this review, we will include such studies if data are available separately for the relevant subset.

Types of interventions

We will investigate the comparison of PCNL versus RIRS for treatment of renal stones in adults. Studies of PCNL procedures included will not be limited based on sheath size, but instead will be evaluated as three subgroups based on size: greater than 24‐Fr (standard PCNL), 15‐Fr to 24‐Fr (mini‐PCNL and minimally invasive PCNL), and less than 15‐Fr (ultra‐mini‐, mini‐micro, super‐mini‐, and micro‐PCNL). Renal stones of all sizes will be evaluated in three distinct groups based on diameter: less than 10 mm, 11 mm to 20 mm, and greater than 20 mm). Stone location will also not be limited, but will instead be evaluated in two subgroups: non‐lower pole and lower pole. Studies of RIRS include both flex and semi‐rigid ureteroscopic procedures. Concomitant interventions will have to be the same in the experimental and comparator groups to establish fair comparisons. We defined methods for evaluation and timing of outcome measurements in consultation with clinical content experts.

Experimental interventions

  • Percutaneous nephrolithotomy

Comparator interventions

  • Retrograde intrarenal surgery

Types of outcome measures

We will not use the measurement of the outcomes assessed in this review as an eligibility criterion.

Primary outcomes

  • Stone‐free rate (dichotomous outcome)

  • Major complications (dichotomous outcome)

  • Secondary interventions (dichotomous outcome)

Secondary outcomes

  • Unplanned additional medical visits to emergency/urgent care or outpatient clinic (dichotomous outcome)

  • Hospital length of stay (continuous outcome)

  • Minor complications (dichotomous outcome)

  • Blood transfusions (dichotomous outcome)

  • Procedure time (continuous outcome)

  • Postprocedure drainage tube (dichotomous outcome)

  • Duration of post procedure drainage tube (continuous outcome)

  • Ureteral stricture/injury (dichotomous outcome)

  • Postoperative pain (continuous outcome)

    • Postoperative day (POD) #0

    • POD #1

    • POD #2–7

  • Narcotic analgesic requirements (continuous outcome if reported in morphine equivalents, dichotomous outcome if reported as yes/no)

  • Quality of life (Wisconsin Quality of Life Questionnaire) (continuous outcome)

  • Primary treatment failure (dichotomous outcome)

Method and timing of outcome measurement

Stone‐free rate

  • Participants with documented passage of all stones of a given size from the kidney and ureter based on imaging (non‐contrast CT, KUB), as determined by the investigators.

  • Outcome will be assessed up to 90 days following PCNL or RIRS.

  • We will consider a 5% absolute difference in stone clearance as clinically important.

Major complications

  • Participants developing intraoperative or postoperative complications requiring additional surgical or radiological intervention or complications that are life‐threatening, causing single‐ or multi‐organ dysfunction, or death.

  • Outcome will be assessed using Clavien‐Dindo classification, and complications categorized as grade III or higher will be considered 'major' and included.

  • We will consider a 5% absolute difference in major complication rate as clinically important.

Secondary interventions

  • Unplanned additional procedures or treatments needed to attain successful stone clearance or to treat intraoperative or postoperative complications following completion of the initial procedure.

  • Outcome will be assessed up to 90 days following PCNL or RIRS.

  • We will consider a 5% absolute difference in retreatment rates as clinically important.

Unplanned additional medical visits

  • Participants requiring unplanned additional medical care in an outpatient clinic or urgent care setting postoperatively.

  • Outcome will be assessed up to 90 days following PCNL or RIRS.

  • We will consider a 5% absolute difference in unplanned additional medical visits to be clinically important.

Hospital length of stay

  • Participants requiring inpatient hospital care beyond the expected postoperative and postanesthetic course.

  • Outcome will be assessed based on individual study reporting.

  • We will consider a mean difference of one day (24 hours) to be clinically important.

Minor complications

  • Participants with any deviation from the normal postoperative course without the need for surgical or radiologic intervention, including wound infections, blood transfusions, and need for total parenteral nutrition.

  • Outcome will be assessed using Clavien‐Dindo classification, and complications categorized as grade I or II will be considered 'minor' and included.

  • We will consider a 5% absolute difference in minor complication rate as clinically important.

Blood transfusions

  • Administration of packed red blood cells (RBCs) in units for the management of intraoperative blood loss.

  • Outcome will be assessed based on individual study reporting.

  • We will consider a mean difference of 1 unit of packed RBCs as clinically important.

Procedure time

  • Length of time from opening incision (PCNL) or ureteroscope insertion (RIRS) to incision closure (PCNL) or ureteroscope removal (RIRS) as measured in minutes.

  • Outcome will be assessed with recorded minutes for intraoperative PCNL or RIRS procedure time.

  • We will consider a mean difference of 0.5 hours as clinically important.

Postprocedure drainage tube or stent: reported in study

  • Participants requiring placement of post procedure nephrostomy tube for clearance of retained stone fragments following PCNL or RIRS.

  • Outcome will be assessed based on individual study reporting.

  • We will consider a 5% absolute difference in need for post procedure drainage tube placement as clinically important.

Duration of post procedure drainage tube or stent

  • Length of time in days for nephrostomy tube placement for clearance of retained stone fragments following PCNL or RIRS.

  • Outcome will be assessed for seven days following PCNL or RIRS.

  • We will consider a mean difference of one day (24 hours) to be clinically important.

Ureteral stricture/injury: reported in study

  • Participants developing postoperative symptomatic ureteral stricture or injury regardless of need for additional interventions for management.

  • Outcome will be assessed within an indefinite timeframe following PCNL or RIRS.

  • We will consider a 5% absolute difference to be clinically important.

Postoperative pain

  • Participants with notable subjective physical pain postoperatively, specifically related to incision sites, nephrostomy tube placement, or other surgical interventions as assessed by patient subjective pain reporting using visual analogue or numerical scale.

  • Outcome will be assessed and preset intervals for a total of seven days following PCNL or RIRS (POD #0, POD #1, POD #2–7)

  • We will consider a mean difference of 1 point on VAS or numerical scale to be clinically important.

Narcotic analgesic requirements: morphine equivalents

  • Participants requiring narcotic medications for postoperative pain management following PCNL or RIRS.

  • Outcome will be assessed for seven days following PCNL or RIRS.

  • We will consider a difference of 3 morphine equivalents to be clinically important.

Quality of life

  • Participants reporting a mean change from baseline or final mean value measured using a validated scale, such as Wisconsin Quality of Life Questionnaire (Diamond 1999).

  • Outcome will be assessed for up to 90 days following PCNL or RIRS.

  • We will consider a clinically important mean difference in quality of life scores based on the specific scale used.

Primary treatment failure

  • Inability to complete the initial planned procedure due to any reason, including anatomic challenges, intraoperative complications, or limitations in accessing the renal stone targeted for treatment.

  • Participants with documented passage of all stones of a given size from the kidney and ureter based on imaging (non‐contrast CT, KUB), as determined by the investigators.

  • Outcome will be assessed for 90 days following PCNL or RIRS.

  • We will consider a 5% absolute difference to be clinically important.

Search methods for identification of studies

We will perform a comprehensive search with no restrictions on the language of publication or publication status. We plan to rerun searches within three months prior to anticipated publication of the review.

Electronic searches

We will search the following sources from inception of each database.

  • The Cochrane Library (via Wiley)

    • Cochrane Database of Systematic Reviews (CDSR)

    • Cochrane Central Register of Controlled Trials (CENTRAL)

  • MEDLINE (via Ovid)

  • Embase (via Elsevier)

  • Scopus

We will also search the following.

If we detect additional relevant key words during any of the electronic or other searches, we will modify the electronic search strategies to incorporate these terms and document the changes.

Searching other resources

We will try to identify other potentially eligible trials or ancillary publications by searching the reference lists of retrieved included trials, reviews, meta‐analyses, and health technology assessment reports. We will also contact study authors of included trials to identify any further studies that we may have missed. We will contact drug/device manufacturers for ongoing or unpublished trials. We will search abstract proceedings for the last three years (2017 to 2019) of the following relevant meetings: AUA, EAU, Société Internationale d'Urologie, and World Congress of Endourology.

Data collection and analysis

Selection of studies

We will use reference management software (EndNote) to identify and remove potential duplicate records. Two review authors (LS, MD) will independently scan the abstract, title, or both, of remaining records retrieved, to determine which studies should be assessed further. Two review authors (LS, MD) will investigate all potentially relevant records as full text; map records to studies; and classify studies as included studies, excluded studies, studies awaiting classification, or ongoing studies in accordance with the criteria for each provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). We will resolve any discrepancies through consensus or recourse to a third review author (PD). If resolution of a disagreement is not possible, we will designate the study as 'awaiting classification' and we will contact study authors for clarification. We will document reasons for exclusion of studies that may have reasonably been expected to be included in the review in a 'Characteristics of excluded studies' table. We will present an adapted PRISMA flow diagram showing the process of study selection (Liberati 2009).

Data extraction and management

We will develop a dedicated data abstraction form that we will pilot test ahead of time.

For studies that fulfill inclusion criteria, two review authors (LS, MD) will independently abstract the following information, which we will provide in the 'Characteristics of included studies' table.

  • Study design

  • Study dates (if dates are not available then this will be reported as such)

  • Study settings and country

  • Participant inclusion and exclusion criteria

  • Participant details, baseline demographics

  • Number of participants by study and by study arm

  • Details of relevant experimental and comparator interventions, such as lithotriptor, laser fiber, power setting, repetition, fragment retrieval method, postoperative stent or catheter placement (or both), and imaging modality used immediately following the procedure to confirm successful stone clearance

  • Definitions of relevant outcomes, and method (e.g. type of imaging modality) and timing of outcome measurement as well as any relevant subgroups

  • Study funding sources

  • Declarations of interest by primary investigators

We will extract outcomes data relevant to this Cochrane Review as needed for calculation of summary statistics and measures of variance. For dichotomous outcomes, we will attempt to obtain numbers of events and totals for population of a 2 × 2 table, as well as summary statistics with corresponding measures of variance. For continuous outcomes, we will attempt to obtain means and standard deviations or data necessary to calculate this information.

We will resolve any disagreements by discussion, or if required, by consultation with a third review author (PD).

We will provide information, including trial identifier, about potentially relevant ongoing studies in the 'Characteristics of ongoing studies' table.

We will attempt to contact authors of included studies to obtain key missing data as needed.

Dealing with duplicate and companion publication

In the event of duplicate publications, companion documents, or multiple reports of a primary study, we will maximize yield of information by mapping all publications to unique studies and collating all available data. We will use the most complete dataset aggregated across all known publications. In case of doubt, we will give priority to the publication reporting the longest follow‐up associated with our primary or secondary outcomes.

Assessment of risk of bias in included studies

Two review authors (LS, MD) will assess the risk of bias of each included study independently. We will resolve disagreements by consensus, or by consultation with a third review author (PD).

We will assess risk of bias using Cochrane's 'Risk of bias' assessment tool (Higgins 2011b). We will assess the following domains:

  • random sequence generation (selection bias);

  • allocation concealment (selection bias);

  • blinding of participants and personnel (performance bias);

  • blinding of outcome assessment (detection bias);

  • incomplete outcome data (attrition bias);

  • selective reporting (reporting bias);

  • other sources of bias.

We will judge risk of bias domains as 'low risk', 'high risk', or 'unclear risk' and will evaluate individual bias items as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b). We will present a 'Risk of bias' summary figure to illustrate these findings.

For performance bias (blinding of participants and personnel) and detection bias (blinding of outcome assessment), we will evaluate the risk of bias separately for each outcome, and we will group outcomes according to whether measured subjectively or objectively when reporting our findings in the 'Risk of bias' tables.

We will define the following endpoints as patient self‐assessed:

  • postoperative pain;

  • quality of life.

We will define the following endpoints as investigator‐adjudicated:

  • stone clearance rate;

  • major complications;

  • minor complications.

We will define the following endpoints as objective:

  • secondary interventions;

  • unplanned additional medical visits to emergency/urgent care or outpatient clinic;

  • procedure time;

  • narcotic analgesic requirements;

  • blood transfusion;

  • placement of post procedure drainage tube or stent;

  • duration of post procedure drainage tube or stent;

  • hospital length of stay;

  • ureteric stricture or injury;

  • primary treatment failure.

We will also assess attrition bias (incomplete outcome data) on an outcome‐specific basis, and will present the judgment for each outcome separately when reporting our findings in the 'Risk of bias' tables.

We will further summarize the risk of bias across domains for each outcome in each included study, as well as across studies and domains for each outcome, in accordance with the approach for summary assessments of the risk of bias presented in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b).

Measures of treatment effect

We will express dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs). We will express continuous data as mean differences (MDs) with 95% CIs unless different studies use different measures to assess the same outcome, in which case we will express data as standardized mean differences with 95% CIs. We will express time‐to‐event data as hazard ratios (HRs) with 95% CIs.

Unit of analysis issues

The unit of analysis will be the individual participant. Should we identify cross‐over trials, cluster‐randomized trials, or trials with more than two intervention groups for inclusion in the review, we will handle these in accordance with guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011c).

Dealing with missing data

We will obtain missing data from study authors, if feasible, and will perform intention‐to‐treat (ITT) analyses if data are available; we will otherwise perform available‐case analyses. We will investigate attrition rates (e.g. dropouts, losses to follow‐up, and withdrawals), and will critically appraise issues of missing data. We will not impute missing data.

Assessment of heterogeneity

In the event of excessive heterogeneity unexplained by subgroup analyses, we will not report outcome results as the pooled effect estimate in a meta‐analysis but will provide a narrative description of the results of each study.

We will identify heterogeneity (inconsistency) through visual inspection of forest plots to assess the amount of overlap of CIs, and the I2 statistic, which quantifies inconsistency across studies to assess the impact of heterogeneity on the meta‐analysis (Higgins 2002; Higgins 2003); we will interpret the I2 statistic as follows (Deeks 2011):

  • 0% to 40%: may not be important;

  • 30% to 60%: may indicate moderate heterogeneity;

  • 50% to 90%: may indicate substantial heterogeneity;

  • 75% to 100%: considerable heterogeneity.

When we find heterogeneity, we will attempt to determine possible reasons for it by examining individual study and subgroup characteristics.

Assessment of reporting biases

We will attempt to obtain study protocols to assess for selective outcome reporting.

If we include 10 studies or more investigating a particular outcome, we will use funnel plots to assess small‐study effects. Several explanations can be offered for the asymmetry of a funnel plot, including true heterogeneity of effect with respect to trial size, poor methodological design (and hence bias of small trials), and publication bias. Therefore, we will interpret results carefully.

Data synthesis

We will summarize data using a random‐effects model. We will interpret random‐effects meta‐analyses with due consideration of the whole distribution of effects. In addition, we will perform statistical analyses according to the statistical guidelines contained in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). For dichotomous outcomes, we will use the Mantel‐Haenszel method; for continuous outcomes, we will use the inverse variance method; and for time‐to‐event outcomes, we will use the generic inverse variance method. We will use Review Manager 5 software to perform analyses (Review Manager 5).

Subgroup analysis and investigation of heterogeneity

We expect the following characteristics to introduce clinical heterogeneity, and plan to carry out subgroup analyses with investigation of interactions:

  • PCNL access caliber:

    • greater than 24‐Fr;

    • 15‐Fr to 24‐Fr;

    • less than 15‐Fr;

  • number of stones (solitary versus multiple);

  • stone location (lower pole versus non‐lower pole);

  • stone size (20 mm or less versus greater than 20 mm).

We will use the test for subgroup differences in Review Manager 5 to compare subgroup analyses if there are sufficient studies (Review Manager 5).

Sensitivity analysis

We plan to perform sensitivity analyses to explore the influence of the following factors (when applicable) on effect sizes:

  • restricting the analysis by taking into account risk of bias, by excluding studies at 'high risk' or 'unclear risk';

  • stone‐free rate by fragment retention. In our primary analysis, we will apply the definition of stone clearance used by the investigators. We will also perform secondary analysis using definitions of:

    • less than 4 mm stone fragment retention visualized by any imaging modality;

    • less than 2 mm stone fragment retention visualized by any imaging modality;

    • totally stone free by CT scan (stone‐free defined as no remaining stones in the collecting system).

'Summary of findings' table

We will present a 'Summary of findings' table reporting the following outcomes listed according to priority.

  • Stone‐free rate (dichotomous outcome)

  • Major complications (dichotomous outcome)

  • Secondary interventions (dichotomous outcome)

  • Unplanned additional medical visits to emergency/urgent care or outpatient clinic (dichotomous outcome)

  • Hospital length of stay (continuous outcome)

  • Ureteral stricture/injury (dichotomous outcome)

  • Quality of life (Wisconsin Quality of Life Questionnaire) (continuous outcome)

We will present the overall quality of the evidence for each of the above outcomes according to the GRADE approach, which takes into account five criteria related to internal validity (risk of bias, inconsistency, imprecision, publication bias), and external validity, such as directness of results (Guyatt 2008). For each comparison, two review authors (LS, MD) will independently rate the quality of evidence for each outcome as 'high', 'moderate', 'low', or 'very low' using GRADEpro GDT. We will resolve any discrepancies by consensus, or, if needed, by arbitration by a third review author (PD). For each comparison, we will present a summary of the evidence for the main outcomes in a 'Summary of findings' table, which will provide key information about the best estimate of the magnitude of the effect in relative terms and absolute differences for each relevant comparison of alternative management strategies; numbers of participants and studies addressing each important outcome; and the rating of the overall confidence in effect estimates for each outcome (Guyatt 2011; Schünemann 2011). If meta‐analysis is not possible, we will present results in a narrative 'Summary of findings' table.