Impact of Surgical Factors on Robotic Partial Nephrectomy Outcomes: Comprehensive Systematic Review and Meta-Analysis

Author's Accepted Manuscript Impact of Surgical Factors on Robotic Partial Nephrectomy Outcomes: Comprehensive Systematic Review and Meta-analysis Giovanni E. Cacciamani , Luis G. Medina , Tania Gill , Andre Abreu , Renè Sotelo , Walter Artibani , Inderbir S. Gill

PII: DOI: Reference:

S0022-5347(18)42791-7 10.1016/j.juro.2017.12.086 JURO 15519

To appear in: The Journal of Urology Accepted Date: 19 December 2017 Please cite this article as: Cacciamani GE, Medina LG, Gill T, Abreu A, Sotelo R, Artibani W, Gill IS, Impact of Surgical Factors on Robotic Partial Nephrectomy Outcomes: Comprehensive Systematic Review and Meta-analysis, The Journal of Urology® (2018), doi: 10.1016/j.juro.2017.12.086. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.

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Impact of Surgical Factors on Robotic Partial Nephrectomy Outcomes: Comprehensive Systematic Review and Meta-analysis

3 4 Giovanni E. Cacciamani 1,2, Luis G. Medina 1, Tania Gill 1, Andre Abreu 1, Renè Sotelo1, Walter Artibani 2 and Inderbir S. Gill 1,*

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USC Institute of Urology & The Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA and the 2Department of Urology, University of Verona, Verona, Italy

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Running title: Meta-analysis of the impact of surgical factors on outcomes of robotic partial nephrectomy

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Total words: Abstract: 335; Text: 3,861 References: 116 Tables: 1 Figures: 9

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Keywords: kidney cancer, renal neoplasia, renal neoplasia, Partial nephrectomy, robot-assisted partial nephrectomy, robotic partial nephrectomy, laparoscopy, robotics.

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*Corresponding Author Inderbir S. Gill, MD Catherine & Joseph Aresty Department of Urology USC Institute of Urology Keck School of Medicine University of Southern California, Los Angeles, CA Email: [email protected]

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Abstract Purpose: Utilization of robotic partial nephrectomy (RPN) has increased significantly. We report a literature-wide systematic review and cumulative meta-analysis to critically evaluate the impact of

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surgical factors on the operative, peri-operative, functional, oncological and survival outcomes of RPN.

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Materials & Methods: All English-language publications on RPN comparing various surgical approaches were evaluated. We followed the Preferred Reporting Items for Systematic Review and

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Meta-Analyses (PRISMA) statement and the Agency for Healthcare Research and Quality (AHRQ)

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guidelines to evaluate Pubmed®, Scopus® and Web of Science® databases (01/01/2000–10/31/2016,

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updated 06/2017). Weighted mean difference (WMD) and odds ratio (OR) compared continuous and

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dichotomous variables, respectively. Sensitivity analyses were performed as needed. To condense the

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sheer volume of analyses, for the first time, data are presented using novel summary forest plots.

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PROSPERO registration number CRD42017062712.

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Results: Our meta-analysis included 20,282 patients. Open PN versus RPN: RPN was superior for

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blood loss (WMD:81.98; p <0.00001), transfusions (OR:1.81; p<0.001), complications (OR:1.87;

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p<0.00001), hospital stay (WMD:2.26; p=0.001), readmissions (OR:2.58; p=0.005), latest eGFR %

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decrease (WMD: 0.37; p = 0.04), overall mortality (OR:4.45; p<0.0001) and recurrence rate (OR:5.14;

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p<0.00001). Sensitivity analyses adjusting for baseline disparities revealed findings similar to above. RPN

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versus laparoscopic PN: RPN was superior for ischemia time (WMD:4.07; p<0.0001), conversion rate

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(OR:2.25; p=0.002), intraoperative (OR:2.07; p>0.0001) and postoperative complications (OR:1.25;

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p=0.0003), positive margins (OR:1.73; p<0.0001), latest eGFR % decrease (WMD:-1.97; p=0.02) and

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overall mortality (OR:2.98; p=0.04). Hilar control techniques, selective and unclamped, are effective

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alternatives to clamped RPN. An important limitation is the overall sub-optimal level of evidence (LOE)

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of publications in the RPN field. No level I prospective randomized data are available; Oxford LOE was

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level II, III and IV in 5%, 74% and 21% of publications, respectively. No study indexed functional

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outcomes to volume of parenchyma preserved.

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Conclusion: Based on the contemporary literature, our comprehensive meta-analysis indicates that RPN delivers mostly superior, and at a minimum equivalent, outcomes compared to open and

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laparoscopic PN. Robotics has now matured into an excellent approach for performing PN surgery for

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renal masses.

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Introduction

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Partial nephrectomy (PN) is considered the surgical treatment of choice for clinical T1 tumors, becoming an imperative indication in patients with solitary kidney, compromised renal function and

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bilateral tumors [1-3]. With increasing world-wide experience, robotic PN (RPN) has demonstrated

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technical efficacy and good clinical outcomes, comparable to open PN (OPN) and laparoscopic PN (LPN)

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[4]. Although RPN surgery is now increasingly widely performed, there remains a lack of consensus

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amongst some concerning the performance of RPN vis-a-vis OPN and LPN [5]. In order to be widely

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accepted amongst surgeons, advancements in technology must show an improvement in clinical efficacy

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over previous standards-of-care.

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For PN surgery, operative outcomes are related to various factors, which may be broadly divided

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into 2 categories: surgical factors (surgical approaches) and host factors (patient characteristics and

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tumor characteristics). In this manuscript, we evaluate on impact of surgical factors on RPN outcomes.

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Compared to prior meta-analyses which were somewhat limited in scope and depth, ours is the first to

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provide a comprehensive look at the entire field of RPN surgery. We performed a comprehensive

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systematic review and cumulative meta-analysis of the world-wide English literature on RPN to critically

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evaluate the impact of the different surgical approaches and techniques on the operative, peri-

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operative, functional, oncological and survival outcomes.

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Methods Search Strategy: For this systematic review, we followed the Preferred Reporting Items for Systematic Review and Meta- Analyses (PRISMA) statement [6] and rated strength of evidence using the

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scheme recommended by Methods and Guide for effectiveness and comparative Effectiveness Review

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of the Agency for Healthcare Research and Quality (AHRQ) [7]. Pubmed®, Scopus® and Web of Science®

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databases were searched systematically for all full-text English language articles on the treatment of

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renal masses in humans, using the terms Partial nephrectomy published between January 1, 2000 and

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October 31, 2016; a complete update of the searches was done in June 2017. References were manually

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reviewed to identify supplementary studies of interest. This study is registered with PROSPERO number

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CRD42017062712.

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Selection of eligible studies and data extraction: Two paired investigators (G.E.C. and L.G.M.) independently screened all articles focusing the research on robotic PN surgery (figure 1). The terms

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“robot(ic)-assisted” and “robotic” were used interchangeably. Any disagreements about eligibility were

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resolved by discussion between the two investigators until consensus was reached. We included only

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comparative and non-comparative studies (clinical trials, prospective or retrospective studies including

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cohort or case-control series) reporting the impact of a specific surgical approach on the outcomes of

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interest (See foot-note of Figure 1 for categories of excluded studies). For quantitative analysis, we

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considered only those multi-institutional studies which reported data never published in participating

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single-center studies. When an institution published multiple papers with entire overlapping surgical

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periods on the same topic, we considered only the latest published paper. However, studies from the

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same institution with entire or partially overlapping surgical periods, but considering different study

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populations were included in the analysis. Moreover, in order to assess the overlapping studies bias,

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meta regression models were performed. Studies analyzing national databases were excluded due to

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high risk of overlapping data.

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All data retrieved from the systematically-reviewed studies were recorded in an electronic database. Specifically, the following baseline characteristics were recorded: age, gender, body mass

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index (BMI), American Society of Anesthesiologist (ASA) score; serum creatinine, estimated glomerular

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filtration rate (eGFR); tumor side (right, left, bilateral), tumor size (maximum diameter), tumor location

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(anterior, posterior; hilar; upper-, mid-, lower-pole); T-stage (T1a-T4); and nephrometry scores such as

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P.A.D.U.A (Preoperative Aspects and Dimensions Used for an Anatomical score), R.E.N.A.L (Radius.

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Exophytic/endophytic. Nearness to collecting system. Anterior/posterior. Location), Contact surface area

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(CSA) score, Centrality mass index (C-Index). Post-PN renal function was assessed by percent reduction

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in latest estimated glomerular filtration rate (eGFR) as reported in each paper. The PICOTS format

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(Population, Intervention, Comparators, Outcomes, Timing and Setting) scrupulously summarizes our

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research and analysis strategy for evaluating the operative, peri-operative, functional, oncologic and

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survival outcomes (Table 1). We adhered to the Martin Criteria (see Table 1 foot-note for details; also

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see supplementary materials) [8]. All papers were categorized according to the Oxford Level of Evidence

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Working Group 2011 levels of evidence (LOEs) for therapy studies [9].

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Data quality assessment: Two paired investigators (G.E.C. and L.G.M.) independently assessed the risk of bias for all studies using the Newcastle–Ottawa Quality Assessment Scale (NOS) [10]: a total

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score of 5 or less was considered low quality, 6–7 was considered intermediate quality, and 8–9 was

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considered high quality.

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Data analysis: Cumulative meta-analysis of comparative studies was conducted using Review

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Manager®5.3 (Cochrane Collaboration, Oxford, UK) as follows. First, an analysis of comparative baseline

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characteristics was done to identify statistically significant differences between patients who underwent

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different surgical approaches. The weighted mean difference (WMD) and odds ratio (OR) were used to

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compare continuous and dichotomous variables, respectively. All results were reported with 95%

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confidence intervals. Statistical heterogeneity between studies was tested: p > 0.10 and I² < 30 % were

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considered to indicate heterogeneity [11]. Random effects and fixed effects were used in case of

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presence or absence of heterogeneity, respectively. To evaluate publication bias, Egger’s regression

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model and funnel plots were examined. A two-sided p-value < 0.05 was considered statistically

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significant. Due to limitations in the Review Manager v5.3 software, analysis of continuous variables was

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possible only when data were presented as mean and standard deviation (SD). Since some studies

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reported continuous variables in “median” and “interquartile range” or “min/max” range, we used a

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validated mathematical method to estimate “mean” and “SD” [12] . Cumulative meta-analyses of

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baseline characteristics were performed; wherever necessary and feasible, a sensitivity analysis was

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conducted in order to adjust for confounding factors. When available, we used data reported in a

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matched-pair comparison manner (8 papers). Data not suitable for meta-analytic evaluation are

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presented in narrative fashion. Based on precedence in the literature and our sensitivity analysis, we

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selected performance of 70 RPN procedures as the cutoff to distinguish between high- and low-volume

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centers. All data retrieved for baseline and perioperative analyses resulted in the creation of a total of

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428 underlying forest plots and 4 tables (Supplementary Material). Data from these 428 forest plots

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were condensed into 8 summary plots for this manuscript.

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Results

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Evidence synthesis: Our electronic search identified a total of 12,106 papers in PubMed, Scopus and Web of Science (Fig 1). Of these, 1,093 RPN publications were identified for detailed review, which

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yielded 114 case series and 155 comparative studies. For the cumulative meta-analysis, we included only

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comparisons that were reported in at least two peer-reviewed papers. This yielded a total of 98

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comparative papers (out of the 155) on various surgical aspects of RPN (Fig 1 Flow chart): 41 papers

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compared LPN vs RPN [13-53], 23 compared OPN vs RPN [54-76], 10 compared OPN vs LPN vs RPN [77-

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86], 5 compared transperitoneal PN (TP-PN) vs retroperitoneal PN (RP-PN) [87-91], 9 compared off-

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clamp vs on-clamp RPN [92-100] and 10 evaluated various other types of hilar clamping (selective-,

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superselective- and early-unclamping) approaches [98, 101, 102]. Our meta-analysis included a total of

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20,282 patients. No level I evidence is available in this field till date.

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Cumulative meta-analysis: Open vs Robotic PN

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At baseline, the OPN cohort had larger tumors (WMD: 0.36, 95% CI 0.19, 0.54; p = <0.0001), which were more often pT2 (OR: 1.01, 95% CI 0.85, 1.20; p = 0.93) and less often of low R.E.N.A.L. score;

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other baseline characteristics, were similar between OPN and RPN groups (Table 2, supplementary

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materials). We adjusted for both these important baseline differences by performing a sensitivity

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analysis using only studies reporting statistically-similar R.E.N.A.L. scores (see below).

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Figure 2 is the summary plot condensing the cumulative meta-analyses of all available comparative studies comparing OPN versus RPN as regards operative, peri-operative, functional,

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oncological and survival outcomes. Pooled analysis of 9,106 patients indicated the OPN group had

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shorter operative (O.R.) time (WMD: -15.27, 95% CI -23.66, -6.88; p = 0.0004) and warm ischemia time

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(WIT) (WMD: -3.50, 95% -6.53, -0.47; p = 0.02); the RPN group had lesser estimated blood loss (EBL)

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(WMD: 85.01, 95% CI 65.14, 104.87; p < 0.00001) and fewer perioperative transfusions (OR: 1.81, 95% CI

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1.38, 2.39; p < 0.0001). Both groups had similar rates of conversion to RN. Intraoperative complications

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were similar, but RPN group had fewer post-operative complications overall (OR: 1.85, 95% CI 1.64, 2.10;

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p< 0.0001), minor (OR: 1.80, 95% CI 1.56, 2.07; p< 0.00001) and major (OR: 1.55, 95% CI 1.27, 1.90; p=

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0.0001). Hospital stay (LOS) was shorter in the RPN group (WMD: 2.26, 95% CI 1.16, 3.35; p= 0.0001).

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Our meta-analysis indicated lesser % reduction in latest eGFR in the RPN group (WMD: -1.02, 95% CI –

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2.00, -0.03; p = 0.005); a sensitivity analysis evaluating only those studies (n=6) that reported latest eGFR

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% change [54, 58, 60, 63, 66, 76] found that despite similar mean tumor size, RENAL scores and WIT, the

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RPN cohort had superior renal functional outcomes compared to OPN. Positive margin rates were also

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similar (Figure 3). During follow-up, rates of 30 days-readmission (OR: 2.58, 95% CI 1.34, 4.96; p =0.005),

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and overall mortality with follow-up (range 5.1-49 months in RPN group; 12-53 months in OPN group)

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(OR: 4.45, 95% CI 2.20, 8.98; p < 0.0001) and cancer recurrence (OR: 0.04, 95% CI 3.28, 16.62; p = 0.15)

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were lower in the RPN group. Cancer-specific mortality rates at 5 years were similar between cohorts,

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with a trend favoring RPN.

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To adjust for baseline differences in tumor characteristics (OPN cohort had larger tumors, higher rate of pT2 disease), we performed a sensitivity analysis including only those studies (n=14) reporting

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mean/median R.E.N.A.L. scores (WMD: 0.19, 95% CI -0.04, 0.42, p= 0.10). This sub-analysis revealed all

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perioperative, oncological and survival outcomes to be similar to the above pooled cumulative analysis;

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the only difference in the sub-analysis was that O.R. time, WIT and last eGFR % change were also similar

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between groups. Sensitivity analysis of only those single-institution studies (n=7) from the above sub-

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analysis which reported similar R.E.N.A.L scores (WMD: -0.11, 95% CI -0.25, 0.04, p= 0.16), showed that

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all evaluated outcomes paralleled the pooled analysis; additionally, WIT and cancer recurrence rates

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were also similar between the 2 groups (Figure 4). Sensitivity analysis evaluating only those single-

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institution studies (n=10) reporting ≥ 70 RPN cases [55, 60, 68, 69, 71, 73, 75, 76, 80, 83, 85] showed

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similar results to the pooled cumulative analysis; additionally, O.R. time and recurrence rates were also

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similar between groups.

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Figure 5 shows summary sensitivity analyses focusing on studies comparing OPN vs RPN only for complex renal masses [62, 76, 80, 85] (defined as R.E.N.A.L score ≥ 7). OPN and RPN were similar as

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regards O.R. time, intraoperative complications and positive margins. However, RPN had lesser EBL

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(WMD: 66.32, 95% CI 26.06, 106.58, p= 0.001), fewer overall postoperative complications (OR: 2.15, 95%

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CI 1.40, 3.29; p =0.0004) and shorter LOS (WMD: 1.57, 95% CI 1.04, 2.09, p < 0.00001).

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Cumulative meta-analysis: Laparoscopic vs Robotic PN

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Analysis of baseline characteristics showed no differences between the 2 groups except for higher incidence of hilar tumors and higher R.E.N.A.L score in the RPN cohort (WMD: -0.33, 95% CI -0.65,

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-0.00; p= 0.05) (Table 3- supplementary material). Cumulative meta-analysis of all studies comparing

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RPN vs LPN (figure 6) showed both groups were similar as regards O.R. time and EBL; however, RPN was

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superior as regards WIT (WMD: 4.21, 95% CI 2.24, 6.17; p< 0.00001), transfusion rate (OR: 1.37, 95% CI

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1.08, 1.74; p= 0.009), intraoperative complications (OR: 2.05, 95% CI 1.51, 2.80; p< 0.00001) and rates of

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conversion to OPN (OR: 2.61, 95% CI 1.11, 6.15; p= 0.03) and radical nephrectomy (OR: 4.00, 95% CI

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2.23, 7.20 p< 0.00001). The RPN group had similar LOS, but fewer overall post-operative (OR: 1.27, 95%

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CI 1.11, 1.45; p= 0.0003) and major complications (OR: 1.50, 95% CI 1.19, 1.89; p= 0.0006) and lower

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rate of positive margins (OR: 2.01, 95% CI 1.52, 2.66; p < 0.00001). Cumulative meta-analysis of studies

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reporting renal functional outcomes showed the RPN group had a lesser latest eGFR % decrease (WMD:

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-1.97, 95% CI -3.57, -0.36; p = 0.02). However, rates of 30 days readmission, cancer recurrence and

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cancer-specific mortality were similar in the 2 groups over similar range of follow-up (3-27 months).

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We also performed a sub-group analysis of single-institution RPN and LPN studies (n=12)

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reporting ≥ 70 cases. Pooled data analysis showed similar results to the cumulative analysis as regards

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O.R. time, WIT, EBL, LOS and rates of intraoperative, major and minor complications. Both groups were

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similar as regards % eGFR change and positive margin rate. Figure 6 shows the sensitivity analysis considering only studies comparing LPN vs RPN for

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complex renal masses. RPN group had shorter O.R. time (WMD: 27.89, 95 % CI 6.46, 49.29; p = 0.01) and

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WIT (WMD: 1.48, 95 % CI 0.06, 2.90; p = 0.04); both groups were similar as regards EBL, transfusions,

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complication rate (overall, minor, major), positive margins, recurrence and latest eGFR % change.

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Cumulative meta-analysis: Transperitoneal (TP) vs Retroperitoneal (RP) RPN

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Baseline characteristics were similar between groups except for more posteriorly-located tumors in the RP-RPN group (table 4- supplementary materials). Cumulative meta-analysis of all studies

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(n=5) comparing TP-RPN vs RP-RPN showed TP-RPN had higher EBL (WMD: 65.35, 95% CI 7.43, 123.27;

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p= 0.03) and longer O.R. time (WMD: 29.68, 95% CI 3.39, 55.97, p= 0.03). Both groups were similar in all

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other parameters, such as WIT, transfusion, rates of conversion to OPN and RN, LOS, positive margins

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and complications (Figure 8).

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Cumulative meta-analysis: Off-clamp vs On-clamp RPN

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Comparing off-clamp vs on-clamp RPN , baseline characteristics were similar( table 5,

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supplementary materials), except for on-clamp RPN group having higher R.E.N.A.L (WMD: -0.29, 95% CI -

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0.57, -0.01; p = 0.04) and PADUA scores (WMD: -1.30, 95% CI -1.78, -0.81; p < 0.00001). On-clamp group

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had longer O.R. time (WMD: -17.88, 95% CI 31.33, -4.43; p = 0.009); off-clamp group had higher EBL

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(WMD: 47.83, 95% CI 21.40, 74.26; p = 0.0004). Both groups were similar as regards transfusion rates,

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open conversion rates, LOS, positive margins and complications (fig. 9). Renal functional analyses

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demonstrated lesser latest eGFR % decrease in the off-clamp RPN group (WMD: 4.09, 95% CI 1.22, 6.95;

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p= 0.005). Sensitivity analysis focusing only on papers (n=6) reporting statistically-similar R.E.N.A.L.

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scores (off-clamp vs on-clamp R.E.N.A.L. scores, p > 0.05) showed similar outcomes in all variables

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evaluated, except for longer LOS in the on-clamp group (WMD: -0.58, 95% CI -1.04, -0.12; p=0.01).

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Cumulative meta-analysis of studies comparing other hilar clamping techniques was performed

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(supplementary materials). Comparison of selective/super-selective clamp RPN vs main artery clamp

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RPN showed higher EBL in the selective/super-selective group (WMD: 41.06, 95% CI 5.44, 76.68: p=

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0.02). Both groups were similar as regards transfusion rate, LOS, positive margins, complication rates

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and late % change eGFR. Sub-analysis of only studies comparing super-selective versus main artery

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clamping showed superior renal functional preservation (WMD: 9.74, 95% CI 5.03, 14.44: p< 0.0001) in

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the super-selective clamp RPN group; however, there were only 4 studies available for this analysis.

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Comparing early-unclamp versus on-clamp RPN, the latter had longer WIT (WMD: -5.60, 95% CI -5.70, -

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5.50; p = <0.00001) and higher EBL (WMD: 117.19, 95% CI 112.18, 122.20; p < 0.00001). Both groups had

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similar OR time, transfusion rate, complication rate, LOS, positive margins and conversion to radical

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nephrectomy.

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The weight of the currently available English literature indicates that RPN is an efficient choice for

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Discussion

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surgical treatment of small renal masses. Cumulative analysis comparing robotic PN with open and

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laparoscopic PN demonstrate mostly superior, and certainly equivalent, results. This holds true even

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when considering only complex renal masses.

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Pooled analyses of 33 studies comparing OPN and RPN in 9,106 patients indicated superiority of

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RPN in terms of blood loss, transfusion rate, minor and major postoperative complications, hospital stay,

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as well as lesser postoperative functional decrease and lower rates of recurrence, readmission and

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overall mortality. OPN had shorter O.R. times and WIT. We conducted a sub-analysis focusing only on

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the 6 studies reporting eGFR outcomes (Fig 3). In this focused sensitivity analysis, despite similar tumor

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size, tumor complexity and WIT between OPN and RPN groups, eGFR outcomes were superior in the

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RPN group. A second sub-analysis comparing OPN and RPN including only those studies (n=7) reporting

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similar R.E.N.A.L scores, all outcomes evaluated were similar to the pooled analysis. Considering the

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possible confounding effect of smaller studies with fewer number of patients, we performed a

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sensitivity analysis focusing only on larger studies (n=10) involving 70 or more RPN cases; again, results

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favored RPN. Prior systematic reviews and meta-analyses of RPN have been somewhat limited in scope.

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For example, the most recent RPN meta-analysis, which evaluated only 19 studies (we evaluate 33

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studies) comparing OPN and RPN concluded that, although RPN had lower comorbidity and better renal

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function, data about mortality were lacking [103]. For the first time, our systematic review assesses

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survival data, which appear to favor RPN, even if positive margin rates were similar between the two

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approaches.

Cumulative meta-analysis of 51 studies comparing RPN and LPN in 8,113 patients shows that

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RPN has shorter WIT, fewer transfusions and intra-/post-operative complications, lower rates of

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conversion to open surgery and radical nephrectomy and superior renal functional outcomes, positive

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margins and overall mortality rate. The above represent considerable real-life advantages for the

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patient. We did note that our meta-analysis did not identify a direct relationship between complications

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and increased hospital stay; as such, it is likely that some of the complications recorded in the pooled

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analysis may have occurred after hospital discharge. Although there were no statistically significant

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differences in O.R. time, EBL, LOS, cancer-specific mortality and recurrence rates, the trend favored RPN.

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The lower WIT during RPN is likely due to the greater robotic range-of-motion, allowing more efficient

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suturing and renorrhaphy. Similar to our findings, RPN has been previously correlated with decreased

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positive margin rates, complications, LOS and eGFR, as also lower rates of conversion to open surgery

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and radical nephrectomy [104].

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We specifically measured surgical approaches against tumor complexity. After controlling for

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tumor complexity, compared to OPN and LPN, RPN delivered at a minimum similar, if not mostly

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superior, results in terms of peri-operative and oncological outcomes. This sub-analysis is particularly

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useful in eliminating tumor complexity as a source of bias when evaluating surgical outcomes, thereby

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making our results stronger. In particular, when comparing OPN and RPN for complex tumors in 745

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patients, EBL, overall complications and hospital stay were lesser in the RPN group. Conversely, when

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comparing LPN vs RPN for complex tumors in 888 patients, RPN was associated with decreased O.R.

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time and LOS. Thus, although studies on complex tumors are few and the level of evidence low, we

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made every attempt to adjust for this important parameter, within the limitations of the available data.

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This suggests that the superior results of RPN may not be entirely ascribed to differences in tumor

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complexity, an important finding.

Our meta-analysis on trans- vs retro-peritoneal RPN included 889 patients, almost doubling the

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number of patients from prior meta-analyses [105]. Differences were higher EBL and longer O.R. time in

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the transperitoneal group; both approaches were similar for all other parameters evaluated. Various

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techniques of hilar control, off-clamp, selective/super-selective clamp and early-unclamp, are safe and

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feasible approaches to RPN surgery, with similar transfusion rates, complications and oncological

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outcomes compared to main artery clamping.

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Built upon 428 underlying Forest plots (a,b,c,d,e,f Supplementary Material), our meta-analysis represents the most up-to-date and complete evidence from the literature about the impact of surgical

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factors on RPN outcomes. Also, our systematic review satisfied quality assessment criteria [106]. Novel

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aspects of our study include the condensed presentation of data using summary plots, and our

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evaluation of parameters not assessed in prior meta-analyses, such as rates of readmission, recurrence

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and overall and cancer-specific mortality. Nevertheless, our meta-analysis has limitations. To match

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baseline tumor characteristics as much as possible, we performed multiple sensitivity analyses based on

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R.E.N.A.L score; yet, one cannot entirely eliminate the impact of surgeon-based selection bias in the

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multiple cohorts analysed herein. Also, we are unable to distinguish between the varying levels of

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surgeon expertise amongst publications. Reportedly, robotics has a shorter learning curve than LPN [25,

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47, 107]. With increasing experience, RPN surgeons can tackle increasingly complex tumors [108],

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however, neither the factors that define RPN expertise, nor the RPN learning curve, have been

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elucidated. As regards renal functional outcomes, although we performed sensitivity analyses assessing

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the impact of tumor size/complexity and WIT on eGFR outcomes, no reported RPN versus OPN

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comparative study indexed eGFR outcomes against preserved parenchymal volume. Given that

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vascularized remnant nephron mass is a primary driver of post-PN functional recovery, alongside pre-PN

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function and prolonged ischemia time, this absence of kidney volume data remains a significant lacuna

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in the literature. Renal functional outcomes in our meta-analysis reflect the latest available eGFR %

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change; this time period differed amongst various studies, introducing heterogeneity. To correct for the

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heterogeneity introduced by baseline variations in tumor complexity amongst publications, we

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performed multiple sensitivity analyses to attempt to collect a rather homogeneous group of tumors

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with statistically-similar R.E.N.A.L. scores, or other variables we believed useful. Thus, although pooled

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analysis of OPN and RPN indicated superior cancer recurrence rates in RPN group, however, after

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adjustment of RENAL score disparity by sensitivity analysis, the cancer recurrence rates were similar for

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similar RENAL score tumors, as expected. Another shortcoming is the relatively short (~ 5 years) follow-

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up period reported in most papers; since many recurrences occur after 5 years, the oncologic data

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reported herein should be viewed with caution [109]. Finally, no meta-analysis can adequately evaluate

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surgeon preference based on individual technical ability, an ultimately important factor dictating choice

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of surgical approach.

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Finally, an important limitation is the overall sub-optimal level of evidence (LOE) of publications in this field. No level I evidence exists regarding RPN to date. Oxford level of evidence was level II, III and

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IV in 5%, 74% and 21% of publications, respectively. Most studies are relatively small, prospective or

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retrospective comparisons of heterogeneous groups. It appears highly unlikely that prospective

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randomized controlled trial (RCT) data will become available in the near future, if at all. Despite the fact

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that we performed a number of methodological variations (ie. sensitivity analyses), the confounding

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variables (tumor complexity; underlying comorbidities) limit our results. It is recognized that both RCT

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and non-RCT studies have strengths and weaknesses, and that both merit inclusion in systematic

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reviews and meta-analyses. Meta-analyses based on non-RCT observational studies have been noted to

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produce estimates of effects similar to those from meta-analysis based on RCTs. As such, observational

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studies should not be excluded a priori, especially when there is a lack of RCT in a specific research area

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[110], such as the current one. Indeed, our meta-analysis of observational RPN studies does address

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clinically-important aspects of specific, relevant surgical issues, potentially laying the basis for future

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RCTs in this field.

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Conclusion

Our comprehensive systematic review and cumulative meta-analysis indicates that, based on available

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data from the entire contemporary English literature, RPN provides mostly superior, and at a minimum

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equivalent, outcomes compared to OPN across various aspects. Evidence for the superiority of RPN over

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LPN is equally compelling. Robotic partial nephrectomy has now emerged as a safe, effective, even

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preferred, PN surgical approach for treatment of small renal masses.

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FIGURES DESCRIPTION

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Figure 1. Literature Search Strategy: Flow Chart. Our method of evaluating all papers on robotic partial nephrectomy published in the English literature up to June 2017.

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*Exclusion criteria: The following categories of full-text articles were excluded: Reply, commentary and editorial comment; Case Reports; Techniques description; Reviews and meta-analysis; Pediatrics surgery; Non matching articles; Publications from the same institution with overlapping data; Does not provide any outcome of interest; Not relevant for the key questions;

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**Outcomes reported in a minimum of 2 publications

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Note: We adhered to the Martin Criteria (method of accruing data defined, duration of follow-up indicated, outpatient information included, definitions of complications provided, mortality rate and causes of death listed, morbidity rate and total complications indicated, procedure-specific complications included, severity grade used, length of stay data and risk factors included in analysis).

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Figure 2. Open partial nephrectomy (OPN) vs Robotic partial nephrectomy (RPN). Summary forest plot of cumulative metaanalysis of studies reporting operative, perioperative, functional, oncological and survival outcomes. CI = confidence interval; WMD = weighted mean difference: OR = odds ratio

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Figure 3. Latest eGFR % change after OPN versus RPN. Sensitivity analysis forest plot restricted to comparative OPN vs RPN studies reporting eGFR % change data. CI = confidence interval; WMD = weighted mean difference: OR = odds ratio.

Figure 4. OPN versus RPN for similar R.E.N.A.L scores. Summary forest plot of sensitivity meta-analyses of only those studies reporting OPN vs RPN for similar RENAL score tumors. Operative, peri-operative, functional, oncological and survival outcomes data. CI = confidence interval; WMD = weighted mean difference: OR = odds ratio. *Meta-analysis was not possible for cancer-specific mortality rate, since it was reported in only 1 paper. Figure 5. OPN versus RPN for Complex Renal Masses. Summary forest plot of sensitivity meta-analysis of only those OPN vs RPN comparative studies reporting complex renal masses. Operative, peri-operative, functional, oncological and survival outcomes. CI = confidence interval; WMD = weighted mean difference: OR = odds ratio; *Meta-analysis was not possible for the following parameters, since these were reported in only 1 paper: WIT, rates of conversion to RN, readmission, recurrence, overall and cancer-specific mortality.

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Figure 6. Laparoscopic partial nephrectomy (LPN) versus robotic partial nephrectomy (RPN). Summary plot of cumulative meta-analysis. Operative, peri-operative, functional, oncological and survival outcomes. CI = confidence interval; WMD = weighted mean difference: OR = odds ratio.

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Figure 7. LPN vs RPN for Complex Renal Masses. Summary forest plot of sensitivity meta-analysis of only those LPN vs RPN comparative studies reporting complex renal masses. Operative, peri-operative, functional, oncological and survival outcomes. CI = confidence interval; WMD = weighted mean difference: OR = odds ratio; *Meta-analysis was not possible for the following parameters, since these were reported in only 1 paper: rates of conversion to OPN, readmission, overall- and cancer-specific mortality.

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Figure 8. Transperitoneal (TP-RPN) vs Retroperitoneal robotic partial nephrectomy (RP-RPN). Summary forest plot of cumulative meta-analysis. Operative, peri-operative, functional, oncological and survival outcomes. CI = confidence interval; WMD = weighted mean difference: OR = odds ratio. *Meta-analysis was not possible for the following parameters, since these were reported in only 1 paper: eGFR % change; rates of readmission, recurrence, overall- and cancer-specific mortality.

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Figure 9. Off-clamp vs On-clamp RPN. Summary plot of cumulative meta-analysis. Operative, peri-operative, functional, oncological and survival outcomes. CI = confidence interval; WMD = weighted mean difference: OR = odds ratio. **Meta-analysis was not possible for the following parameters, since these were reported in only 1 paper: intra-operative complication, readmission, recurrence, overall and cancer-specific mortality rate.

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arterial clamp and main artery clamp techniques, with a minimum follow-up of 1 year. BJU Int, 2015. 115(6): p. 921-8. Comez, K., et al., Partial Nephrectomy for Stage I Renal Cell Carcinoma: On-clamp or Off-clamp? Journal of Urological Surgery, 2016. 3(2): p. 38-41. Peyronnet, B., et al., Off-Clamp versus On-Clamp Robotic Partial Nephrectomy: A Multicenter Match-Paired Case-Control Study. Urol Int, 2017. Furukawa, J., et al., Renal Functional and Perioperative Outcomes of Selective Versus Complete Renal Arterial Clamping During Robot-Assisted Partial Nephrectomy: Early Single-Center Experience With 39 Cases. Surgical Innovation, 2016. 23(3): p. 242-248. Paulucci, D.J., et al., Selective arterial clamping does not improve outcomes in robot-assisted partial nephrectomy: a propensity-score analysis of patients without impaired renal function. BJU Int, 2017. 119(3): p. 430-435. Xia, L., et al., Systematic Review and Meta-Analysis of Comparative Studies Reporting Perioperative Outcomes of Robot-Assisted Partial Nephrectomy Versus Open Partial Nephrectomy. J Endourol, 2017. 31(9): p. 893-909. Choi, J.E., et al., Comparison of perioperative outcomes between robotic and laparoscopic partial nephrectomy: a systematic review and meta-analysis. Eur Urol, 2015. 67(5): p. 891-901. Xia, L., et al., Transperitoneal versus retroperitoneal robot-assisted partial nephrectomy: A systematic review and meta-analysis. Int J Surg, 2016. 30: p. 109-15. Oxman, A.D. and G.H. Guyatt, Validation of an index of the quality of review articles. J Clin Epidemiol, 1991. 44(11): p. 1271-8. Haseebuddin, M., et al., Robot-assisted partial nephrectomy: evaluation of learning curve for an experienced renal surgeon. J Endourol, 2010. 24(1): p. 57-61. Krane, L.S., et al., Does experience in creating a robot-assisted partial nephrectomy (RAPN) programme in an academic centre impact outcomes or complication rate? BJU Int, 2013. 112(2): p. 207-15. Fisher, R.A., et al., A-PREDICT: A phase II study of axitinib in patients with metastatic renal cell cancer unsuitable for nephrectomy (CRUKE/11/061). Journal of Clinical Oncology, 2014. 32(15_suppl): p. TPS4597-TPS4597. Shrier, I., et al., Should meta-analyses of interventions include observational studies in addition to randomized controlled trials? A critical examination of underlying principles. Am J Epidemiol, 2007. 166(10): p. 1203-9.

AC C

649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 673 674 675 676 677 678 679 680

22

ACCEPTED MANUSCRIPT

INCLUSION CRITERIA IN THE CUMULATIVE META ANALYSIS POPULATION

RI PT

INTERVENTIONS

Age > 18 yrs Diagnoses: urologic neoplasia in adults: • Renal Mass • Robotic Partial Nephrectomy (RPN) • Laparoscopic partial nephrectomy (LPN) • Open partial nephrectomy (OPN) Comparison in the treatment of renal masses included in the list above: • OPN vs RPN • LPN vs RPN • Transperitoneal RPN vs Retroperitoneal RPN • Off clamp RPN vs on clamp RPN • Selective/ super-selective RPN vs on-clamp RPN • Early unclamp RPN vs on clamp RPN Peri-operative outcomes: • Operative times (min) • Estimated blood loss (ml) • Warm Ischemia time (min) • Conversion to open procedure (%) • Conversion to radical nephrectomy (%) • Overall transfusion rate (%) • Overall intraoperative complication (%) • Overall postoperative complication rate (%) • Minor (Clavien-Dindo < III) postoperative complication rate (%) • Major (Clavien-Dindo ≥ III) postoperative complication rate (%) • Length of hospital stay (days) • 90 days readmission rate (%) Functional outcomes: • Renal Function (eGFR % change) Oncological outcomes: • Positive margins (%) • Tumor Recurrence (%) Survival outcomes • Any time overall mortality (%) • Any time cancer specific mortality (%) All available clinical, prospective randomized and non-randomized trials and retrospective comparative studies (cohort or case control series) published between 2000 and 2017 comparing different surgical approaches. For inclusion in the comparative meta- analysis, a given comparison must have been reported in at least two peer-reviewed papers. Any time point and setting

COMPARATORS

EP

TYPE OF STUDIES

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SC

OUTCOMES

TIMING AND SETTING

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Table 1 PICOTS ( Population, Interventions, Comparators, Outcomes, Type of study, Timing and Setting) strategy of research: according to Comparative Effectiveness Reviews of Agency for Healthcare Research and Quality (AHRQ)

10,233 All non-robotic PN articles excluded

RI PT

Identification

ACCEPTED MANUSCRIPT

12,106 articles identified : 3,262 identified from Pubmed 4,727 identified from Scopus 4,117 identified from Web of Science

Screening

1,873 Articles about robotic approach identified

M AN U

SC

886 Full-text articles excluded with reason: Duplicates,; Replies, commentaries and editorial comments; Case Reports; Surgical Techniques description; Reviewes and meta-analysis ; Not maching records

Eligibility

987 articles identified for the eligibility

TE D

106 articles included after updated of literature search

1093 articles identified for the eligibility

EP

824 articles excluded with reason*

AC C

Inclusion

269 articles included in the quantitative synthesis 114 RPN case series 155 RPN comparative studies

98 RPN comparative studies included in the present M-A ** 41 comparing LPN vs RPN 23 comparing OPN vs RPN 10 comparing LPN vs RPN vs OPN 5 comparing Transperitoneal RPN vs Retroperitoneal RPN 9 comparing Off clamp RPN vs on-clamp RPN 8 comparing Selective/Super-selective clamp RPN vs on clamp 2 comparing Early unclamp RPN vs on-clamp

AC C

EP

TE D

M AN U

SC

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ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

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ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT R.E.N.A.L. SCORE,mean Subtotal (95% CI) 567 747 Heterogeneity of 6 studies: (P= 0,17); I² = 34%; WMD: -0.11 [-0.25, 0.04] OPERATIVE TIME, min Subtotal (95% CI) 487 633 Heterogeneity of 6 studies: (P < 0.00001); I² = 87%; WMD: 2.59 [-17.96, 23.13] ESTIMATED BLOOD LOSS, ml Subtotal (95% CI) 387 533 Heterogeneity of 5 studies : (P= 0.0001); I² = 83%; WMD: 93.66[34,17, 152.15] WARM ISCHEMIA TIME, ml Subtotal (95% CI) 299 358 Heterogeneity of 3 studies : (P :0.001); I² = 85%; WMD: -1.50[-5.13, 2.14] CONVERSION TO RADICAL RATE, n (%)* Subtotal (95% CI) Heterogeneity: N/A; OR: 1.84 [0.60, 5.60]

9/190

Favor of OPN

RPN n= 747

P :0.16 -1

- 0,5

- 200

0

0,5

1

-100

0

100

200

- 200

-100

0

100

200

0

10

20

P :0.81

P = 0.002

P = 0.42 - 20

5/190 0.005

-10

0.1

0.005

0.1

M AN U

TRANSFUSIONS RATE, n (%) Subtotal (95% CI) 49/272 26/418 Heterogeneity of 4 studies : (P = 0.39); I² = 1%; OR: 3,06 [1.82, 5,16] OVERALL INTRAOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 23/509 21/724 Heterogeneity of 5 studies : (P = 0.89); I² = 0%; OR: 1.32 [0.71, 2.45]

OVERALL POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 155/539 117/724 Heterogeneity of 6 studies : (P = 0.19); I² = 32%; OR: 2.23[1.68, 2.94]

TE D

CLAVIEN-DINDO < 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 109/541 83/721 Heterogeneity of 6 studies : (P = 0.21); I² = 29%; OR: 2.09 [1.52, 2.88]

CLAVIEN-DINDO ≥ 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 47/541 40/721 Heterogeneity of 6 studies : (P = 0.53); I² = 0%; OR: 1.80 [1.13, 2.86]

EP

LENGHT OF HOSPITAL STAYS, days Subtotal (95% CI) 487 633 Heterogeneity of 6 studies : (P < 0.00001); I² = 85%; WMD: 2.11[1.56, 2.66] LATEST POSTOPERATIVE % eGFR DECREASE, ml/min Subtotal (95% CI) 290 290 Heterogeneity of 2 studies : (P = 0.47); I² = 0% WMD: -1.77 [-2.94, -0.60]

AC C

POSITIVE MARGINS RATE, n (%) Subtotal (95% CI) 21/541 24/721 Heterogeneity of 6 studies :(P = 0.71); I² = 0%; OR: 1.28 [0.69, 2.35] CANCER SPECIFIC MORTALITY RATE, n (%)* Subtotal (95% CI) 5/190 Heterogeneity: N/A; OR: 31.68 [0.40, 7.15]

Favor of RPN

RI PT

OPN n= 567

SC

SUBGROUP ANALYSIS n. of patient

1

10

200

P < 0.0001 1

10

200

10

200

P = 0.38

0.005

0.1

1

0.02

0.1

1

P < 0.00001 10

50

P < 0.00001

0.02

0.1

1

10

50

0.02

0.1

1

10

-4

-2

0

2

20

10

0

0.02

0.1

1

10

50

0.005

0.1

1

10

200

0.02

0.1

1

10

P = 0.01 50

P< 0.00001 4

P= 0.003 -10

-20

P = 0.43

3/190

RECURRENCE RATE, n (%) Subtotal (95% CI) 7/246 6/244 Heterogeneity of 2 studies : (P = 0.41); I² = 0%; OR: 1.16 [0.39, 3.50]

P =0.79 50

Favor of ACCEPTED RPN MANUSCRIPT OPN

OPN (Complex Tumors) n= 370

(Complex Tumors) n= 375

OPERATIVE TIME, min Subtotal (95% CI) 333 300 Heterogeneity of 4 studies:(P < 0.000001); I² = 98%; WMD: -18.60 [-58.31, 21.12] ESTIMATED BLOOD LOSS, ml Subtotal (95% CI) 281 290 Heterogeneity of 3 studies: (P = 0.002); I² = 83%; WMD: 66.32 [26.06, 106.58] WARM ISCHEMIA TIME, ml* Subtotal (95% CI) 186 Heterogeneity: Not Applicable; WMD: 1.00 [-0.64, 2.64] CONVERSION TO RADICAL RATE, n (%)* Subtotal (95% CI) 9/190 Heterogeneity: Not Applicable: OR: 1.84 [0.60, 5.60]

181

5/190

Favor of RPN (Complex Tumors)

(Complex Tumors)

P = 0.36 - 200

-100

0

100

200

- 200

-100

0

100

200

- 20

-10

0

10

20

P= 0.001

RI PT

SUBGROUP ANALYSIS n. of patient

0.005

0.1

1

10

TRANSFUSION RATE, n (%) Subtotal (95% CI) 39/279 20/290 Heterogeneity of 3 studies: (P = 0.07); I² = 62%; OR: 3.00 [0.95, 9.53]

0.005

0.1

1

10

200

OVERALL INTRAOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 15/242 11/200 Heterogeneity of 2 studies:(P = 0.59); I² = 47%; OR: 1.24 [0.56, 2.76]

0.005

10

200

SC

P= 0.06

0.1

M AN U

OVERALL POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 85/279 43/290 Heterogeneity of 3 studies: (P = 0.35); I² = 6%; OR: 2.15 [1.40, 3.29] CLAVIEN-DINDO < 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 67/279 32/290 Heterogeneity of 3 studies: (P = 0.63); I² = 0%; OR: 2.36 [1.46, 3.79]

TE D

CLAVIEN-DINDO ≥ 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 18/279 11/290 Heterogeneity of 3 studies: (P = 0.02); I² = 74%; OR: 1.10 [0.21, 5.72]

200

P = 0.59 1

P= 0.0004

0.02

0.1

1

10

0.02

0.1

1

10

0.02

0.1

1

10

50

P= 0.0004 50

P= 0.91 50

P< 0.00001

LENGTH OF HOSPITAL STAY, days Subtotal (95% CI) 318 365 Heterogeneity of 4 studies: (P = 0.08); I² = 56%; WMD: 1.57 [1.04, 2.09]

-4

-2

0

2

LATEST POSTOPERATIVE % eGFR DECREASE, ml/min* Subtotal (95% CI) 190 Heterogeneity: Not Applicable; WMD: 2.20 [0.54, 3.86]

20

10

0

-10

0.02

0.1

1

10

50

EP

190

POSITIVE MARGIN RATE, n (%) Subtotal (95% CI) 12/242 4/220 Heterogeneity of 2 studies:(P = 0.34); I² = 0%; OR: 2.04 [0.64, 6.52]

4

-20

P = 0.23

3/190

0.005

0.1

1

10

200

RECURRENCE RATE, n (%)* Subtotal (95% CI) 6/190 Heterogeneity: Not Applicable; OR: 1.52 [0.42, 5.46]

4/190

0.02

0.1

1

10

50

AC C

CANCER SPECIFIC MORTALITY RATE, n (%)* Subtotal (95% CI) 5/190 Heterogeneity: Not Applicable OR: 1.68 [0.40, 7.15]

ACCEPTED MANUSCRIPT

Favor of LPN

RPN n= 4289

OPERATIVE TIME, min Subtotal (95% CI) 2235 2289 Heterogeneity of 28 studies:(P < 0.00001); I² = 98%; WMD: 7.68 [-10.47, 25.84] ESTIMATED BLOOD LOSS, ml Subtotal (95% CI) 2147 2147 Heterogeneity of 27 studies: (P < 0.00001); I² = 95%; WMD: 23.28 [-10.09, 56.65] WARM ISCHEMIA TIME, ml Subtotal (95% CI) 1640 1798 Heterogeneity of 22 studies: (P < 0.0001); I² = 89%; WMD: 4.21 [2.24, 6.17] CONVERSION TO OPEN RATE, n (%) Subtotal (95% CI) 59/1869 16/2234 Heterogeneity of 17 studies: (P 0.05); I² = 42%; OR: 2.61 [1.11,6.15] CONVERSION TO RADICAL RATE, n (%) Subtotal (95% CI) 49/1964 10/2695 Heterogeneity of 18 studies: (P = 0.47); I² = 0%; OR: 4.00 [2.23, 7.20]

P = 0.41 - 200

-100

0

- 200

-100

0

- 20

-10

0

OVERALL INTRAOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 113/1853 66/2390 Heterogeneity of 18 studies:(P = 0.26); I² = 17%; OR: 2.05 [1.51, 2.80]

0.1

1

0.005

0.1

1

0.005

0.1

0.005

1

1

0.02

0.1

1

-4

-2

0

0.005

0.1

1

LATEST POSTOPERATIVE % eGFR DECREASE, ml/min Subtotal (95% CI) 1165 1183 Heterogeneity of 12 studies: (P = 0.008); I² = 57% WMD: -1.97 [-3.57, -0.36]

20

10

0

POSITIVE MARGINS RATE, n (%) Subtotal (95% CI) 128/2529 94/3103 Heterogeneity of 28 studies: (P 0.62); I² = 0%; OR: 2.01 [1.52, 2.66]

0.02

0.1

1

0.005

0.1

1

0.005

0.1

1

0.02

0.1

1

TE D

0.1

EP

AC C

10

200

10

200

10

200

P< 0.00001

0.1

0.02

RECURRENCE RATE, n (%) Subtotal (95% CI) 14/666 7/888 Heterogeneity of 10 studies: (P = 0,26); I² = 24%; OR: 2.36 [0.95, 5.84]

20

P= 0.009

CLAVIEN-DINDO < 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 520/2915 425/3373 Heterogeneity of 33 studies: (P < 0.00001); I² = 65%; OR: 1.12 [0.82, 1.53]

CANCER SPECIFIC MORTALITY RATE, n (%) Subtotal (95% CI) 11/1236 5/2067 Heterogeneity of 8 studies: (P = 0.90); I² = 0%; OR: 2.43 [0.83, 7.12]

10

1

1

OVERALL MORTALITY RATE, n (%) Subtotal (95% CI) 11/1236 5/2067 Heterogeneity of 9 studies: (P = 0.83); I² = 0%; OR: 2.98 [1.05, 8.40]

200

P< 0.00001

0.1

READMISSION RATE, n (%) Subtotal (95% CI) 10/295 5/310 Heterogeneity of 4 studies: (P = 0.06); I² = 59%; OR: 0.92 [0.11, 8.02]

100

P= 0.03

0.005

0.02

LENGTH OF HOSPITAL STAY, days Subtotal (95% CI) 1690 1718 Heterogeneity of 23 studies: (P < 0.00001); I² = 67%; WMD: 0.17 [-0.02, 0.37]

200

P< 0.0001

OVERALL POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 681/2911 647/3373 Heterogeneity of 33 studies: (P = 0.22); I² = 16%; OR: 1.27 [1.11, 1.45]

CLAVIEN-DINDO ≥ 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 189/2915 150/3373 Heterogeneity of 33 studies: (P = 0.84); I² = 0%; OR: 1.50 [1.19, 1.89]

100

P= 0.17

M AN U

TRANSFUSION RATE, n (%) Subtotal (95% CI) 235/2615 174/3263 Heterogeneity of 28 studies: (P = 0.53); I² = 0%; OR: 1.37 [1.08, 1.74]

Favor of RPN

RI PT

LPN n= 3824

SC

SUBGROUP ANALYSIS n. of patients

10

200

10

50

10

50

P= 0.0003

P= 0.47

P= 0.0006 10

50

P= 0.08 2

4

P= 0.94 10

200

P= 0.02 -10

-20

P< 0.00001 10

50

P= 0.04 10

200

P= 0.11 10

200

P= 0.06 10

50

Favor of ACCEPTED RPN MANUSCRIPT LPN (Complex Tumors) n= 468

OPERATIVE TIME, min Subtotal (95% CI) 355 369 Heterogeneity of 3 studies:(P = 0.002); I² = 84%; WMD: 27.89 [6.49, 49.29] ESTIMATED BLOOD LOSS, ml Subtotal (95% CI) 355 369 Heterogeneity of 3 studies: (P = 0.004); I² = 95%; WMD: 8.64 [-37.43, 54.70] WARM ISCHEMIA TIME, ml Subtotal (95% CI) 355 369 Heterogeneity of 3 studies: (P = 0.67); I² = 0%; WMD: 1.48 [0.06, 2.90] CONVERSION TO RADICAL RATE, n (%) Subtotal (95% CI) 26/355 4/369 Heterogeneity of 3 studies: (P = 0.05); I² = 73%; OR: 6.19 [2.19, 17.51] TRANSFUSIONS RATE, n (%) Subtotal (95% CI) 38/355 34/369 Heterogeneity of 3 studies: (P = 0.46); I² = 0%; OR: 1.21 [0.74, 1.97]

(Complex Tumors)

P = 0.01 - 200

-100

0

- 200

-100

0

- 20

-10

0

OVERALL POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 108/416 113/468 Heterogeneity of 6 studies: (P = 0.50); I² = 0%; OR: 1.12 [0.82, 1.54] CLAVIEN-DINDO < 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 83/367 87/443 Heterogeneity of 5 studies: (P = 0.69); I² = 0%; OR: 1.15 [0.81, 1.63]

TE D

CLAVIEN-DINDO ≥ 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 18/367 21/443 Heterogeneity of 5 studies: (P = 0.74); I² = 0%; OR: 1.15 [0.58, 2.26] LENGTH OF HOSPITAL STAY, days Subtotal (95% CI) 355 369 Heterogeneity of 3 studies: (P = 0.50); I² = 0%; WMD: 0.27 [0.03, 0.52]

EP

LATEST POSTOPERATIVE % eGFR DECREASE, ml/min Subtotal (95% CI) 355 369 Heterogeneity of 3 studies: (P = 0.70); I² = 0% WMD: -1.19 [-2.87, 0.49]

POSITIVE MARGINS RATE, n (%) Subtotal (95% CI) 355 369 Heterogeneity of 3 studies:(P 0.23); I² = 16%; OR: 1.73 [1.33, 2.26]

AC C

OVERALL MORTALITY RATE, n (%)* Subtotal (95% CI) 0/38 Heterogeneity: (P = 0,83); I² = 0%; OR: 2.98 [1.05, 8.40]

0/38

CANCER SPECIFIC MORTALITY RATE, n (%) Subtotal (95% CI) 0/173 0/170 Heterogeneity of 2 studies: (P = 0,90); I² = 0%; OR: 2.43 [0.83, 7.12] RECURRENCE RATE, n (%) Subtotal (95% CI) 7/317 4/280 Heterogeneity of 2 studies: (P = 0,95); I² = 0%; OR: 1.19 [0.34, 4.17]

100

200

P= 0.71 100

200

P = 0.04 10

20

P = 0.0006

0.005

0.1

1

0.005

0.1

1

10

200

10

200

10

200

10

50

10

50

10

50

P= 0.46

0.005

0.1

M AN U

OVERALL INTRAOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 20/355 11/369 Heterogeneity of 3 studies:(P = 0.59); I² = 0%; OR: 2.07 [1.53, 2.81]

Favor of RPN (Complex Tumors)

RI PT

LPN (Complex Tumors) n= 420

SC

SUBGROUP ANALYSIS n. of patients

0.02

P = 0.59 1

P= 0.47

0.1

1

P= 0.45

0.02

0.1

1

0.02

0.1

1

-4

-2

0

20

10

0

0.02

0.1

1

10

50

0.005

0.1

1

10

200

0.005

0.1

1

10

200

0.02

0.1

1

P= 0.69

P= 0.03 2

4

P= 0.17 -10

-20

P= 0,53

P= 0.79 10

50

ACCEPTED MANUSCRIPT

TRANSPERITONEAL RETROPERITONEAL RPN RPN n= 525 n= 294

ESTIMATED BLOOD LOSS, ml Subtotal (95% CI) 428 178 Heterogeneity of 4 studies: (P < 0.00001); I² = 88%; WMD: 65.35 [7.43, 123.27] WARM ISCHEMIA TIME, ml Subtotal (95% CI) 428 178 Heterogeneity of 4 studies: (P = 0.02); I² = 70%; WMD: -0.62 [-3.84, 2.61] CONVERSION TO OPEN RATE, n (%) Subtotal (95% CI) 6/355 1/118 Heterogeneity of 2 studies: (P = 0.40); I² = 0%; OR: 2.59 [0.44, 15.34] CONVERSION TO RADICAL RATE, n (%) Subtotal (95% CI) 1/73 1/60 Heterogeneity of 2 studies: (P = 0.26); I² = 20%; OR: 0.76 [0.11, 5.33]

P = 0.03 - 200

-100

0

- 500

-250

0

100

200

250

500

- 20

-10

0

10

20

P= 0.03

P = 0.71

P = 0.29

0.005

0.1

1

10

200

1

10

200

1

10

200

10

200

P = 0,78 0.005

0.1

P= 0.89

0.005

0.1

M AN U

TRANSFUSION RATE, n (%) Subtotal (95% CI) 14/412 8/168 Heterogeneity of 3 studies: (P = 0.94); I² = 0%; OR: 0.93 [0.35, 2.46]

RETROPERITONEAL RPN

RI PT

OPERATIVE TIME, min Subtotal (95% CI) 428 178 Heterogeneity of 4 studies: (P < 0.00001); I² = 86%; WMD: 29.68 [3.39, 55.97]

TRANSPERITONEAL RPN

SC

SUBGROUP ANALYSIS n. of patients

0.005

0.1

1

OVERALL POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 47/428 21/178 Heterogeneity of 4 studies: (P = 0.88); I² = 0%; OR: 0.87 [0.49, 1.55]

0.005

0.1

1

10

200

CLAVIEN-DINDO < 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 31/369 13/134 Heterogeneity of 4 studies: (P =0.39); I² = 0%; OR: 0.89 [0.44, 1.80]

0.005

0.1

1

10

200

CLAVIEN-DINDO ≥ 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 10/369 4/134 Heterogeneity of 4 studies: (P = 0.38); I² = 0%; OR: 0.67 [0.22, 2.07]

0.005

0.1

1

10

200

LENGTH OF HOSPITAL STAY, days Subtotal (95% CI) 17/466 9/250 Heterogeneity of 4 studies: (P = 0.01); I² = 85%; WMD: -1.68 [-6.43, 3.07]

-20

-10

0

10

20

0.005

0.1

1

10

200

20

10

0

EP

TE D

OVERALL INTRAOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 10/369 0/134 Heterogeneity of 3 studies: (P = 0.81); I² = 0%; OR: 4.89 [0.61, 39.42]

0/116

LATEST POSTOPERATIVE % eGFR DECREASE, ml/min* Subtotal (95% CI) 57 Heterogeneity: Not Applicable. WMD: 0.60 [-4.79, 5.99]

50

AC C

READMISSION RATE, n (%)* Subtotal (95% CI) 1/97 Heterogeneity: Not Applicable: OR: 3.62 [0.15, 89.92]

POSITIVE MARGIN RATE, n (%) Subtotal (95% CI) 9/428 5/178 Heterogeneity of 4 studies:(P = 0.70); I² = 0%; OR: 0.86 [0.29, 2.49] OVERALL MORTALITY RATE, n (%)* Subtotal (95% CI) 2/296 Heterogeneity: Not Applicable. OR: 1.26 [0.06, 26.63]

0/74

CANCER SPECIFIC MORTALITY RATE, n (%)* Subtotal (95% CI) 1/296 Heterogeneity: Not Applicable. OR: 0.76 [0.03, 18.75]

0/74

RECURRENCE RATE, n (%) 1/355 2/118 Subtotal (95% CI) Heterogeneity of 2 studies: Not Applicable. OR: 0.12 [0.01, 1.36]

P= 0.14

P= 0.65

P= 0.74

P= 0.49

P= 0.49

-10

-20

P = 0.77 0.02

0.1

1

10

50

0.005

0.1

1

10

200

0.005

0.1

1

10

200

0.005

0.1

1

10

200

ACCEPTED MANUSCRIPT SUBGROUP ANALYSIS n. of patient

Off-clamp RPN n= 245

Favor of Off clamp RPN

On-clamp RPN n= 651

OPERATIVE TIME, min Subtotal (95% CI) 237 631 Heterogeneity of 8 studies: (P < 0.00001); I² = 90%; WMD: -17.88 [-31.33, -4.43] ESTIMATED BLOOD LOSS, ml Subtotal (95% CI) 175 563 Heterogeneity of 6 studies: (P < 0.00001); I² = 82%; WMD: 47.83 [21.40, 74.26]

P = 0.009 - 200

-100

0

- 200

-100

0

1

0.005

0.1

CONVERSION TO RADICAL RATE, n (%) Subtotal (95% CI) 3/49 1/218 Heterogeneity of 2 studies: (P = 0.50); I² = 0%; OR: 11.07 [1.56, 78.61]

0.005

0.1

TRANSFUSION RATE, n (%) Subtotal (95% CI) 11/197 31/533 Heterogeneity of 8 studies: (P = 0.89); I² = 0%; OR: 0.98 [0.47, 2.05]

0.005

0.1

OVERALL INTRAOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 0/138 Heterogeneity of 5 studies: Not Applicable

0.005

CLAVIEN-DINDO < 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 5/101 34/267 Heterogeneity of 4 studies: (P = 0.46); I² = 0%; OR: 0.64 [0.23, 1.74]

TE D

CLAVIEN-DINDO ≥ 3 POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 7/176 15/589 Heterogeneity of 7 studies: (P = 0.97); I² = 0%; OR: 0.61 [0.22, 1.68]

LENGTH OF HOSPITAL STAY, days Subtotal (95% CI) 168 548 Heterogeneity of 5 studies: (P < 0.00001); I² = 86%; WMD: -0.71 [-1.54, 0.13]

1/55

EP

READMISSION RATE, n (%)* Subtotal (95% CI) 0/30 Heterogeneity: Not Applicable. OR: 0.76 [0.03, 20.74]

200

100

200

P= 0.68

RI PT

10

200

P= 0.02

1

10

200

1

10

200

1

10

200

1

10

50

1

10

50

1

10

50

SC

P = 0.95

0.1

M AN U

OVERALL POSTOPERATIVE COMPLICATION RATE, n (%) Subtotal (95% CI) 17/178 56/349 Heterogeneity of 7 studies: (P = 0.86); I² = 0%; OR: 0.68 [0.37, 1.28]

100

P = 0.0004

CONVERSION TO OPEN RATE, n (%) Subtotal (95% CI) 4/56 3/118 Heterogeneity of 2 studies: (P = 0.63); I² = 0%; OR: 1.44 [0.26, 8.01]

0/361

Favor of On-clamp RPN

P = 0.23

0.02

0.1

P =0.38

0.02

0.1

P = 0.34

0.02

0.1

P= 0.10 -4

-2

0

2

0.005

0.1

1

10

4

200

P= 0.005 20

POSITIVE MARGINS RATE, n (%) Subtotal (95% CI) 9/188 20/348 Heterogeneity of 7 studies:(P = 0.64); I² = 0%; OR: 0.72 [0.31, 1.71]

0.02

0.1

1

10

50

AC C

LATEST POSTOPERATIVE % eGFR DECREASE, ml/min Subtotal (95% CI) 147 513 Heterogeneity of 6 studies: (P < 0.00001); I² = 87% WMD: 4.09 [1.22, 6.95]

10

0

-10

-20

P = 0.30

OVERALL MORTALITY RATE, n (%)* Subtotal (95% CI) 0/71 Heterogeneity: Not Applicable ; OR: 2.82 [0.15, 51.73]

6/147

0.005

0.1

1

10

200

CANCER SPECIFIC MORTALITY RATE, n (%)* Subtotal (95% CI) 0/53 Heterogeneity: Not Applicable; OR: 2.82 [0.15, 51.73]

6/128

0.005

0.1

1

10

200

0.02

0.1

1

10

50

RECURRENCE RATE, n (%) Subtotal (95% CI) 0/110 6/431 Heterogeneity of 4 studies: Not Applicable; OR: 2.82 [0.15, 51.73]

ACCEPTED MANUSCRIPT ASA (American Society of Anaesthesiologist) BMI (body mass index) CI (confidence interval) EBL (estimated blood loss) eGFR (estimated glomerular filtration rate)

RI PT

LOS (length of stay) LPN (laparoscopic partial nephrectomy) LOE (Level of evidence) OPN (open partial nephrectomy)

SC

OR (odd ratio)

PN (partial nephrectomy) RPN (robotic partial nephrectomy) RCT ( randomized Clinical Trial) RP-PN (retroperitoneal partial nephrectomy) SD (standard deviation)

WIT (warm ischemia time)

TE D

TP-PN (transperitoneal partial nephrectomy)

M AN U

O.R. (operative room)

AC C

EP

WMD (weighted mean difference)

ACCEPTED MANUSCRIPT

2011

Simhan et al (moderate) [3]

2012

Simhan et al (complex) [3]

2012

Stroup et al [4]

2012

Alemozaffar et al [5]

2013

Laydner et al [6]

2012

AC C

LOE

Procedure type

n. of Procedures

4

OPN RPN

234 69

20032010

4

OPN RPN

54 27

20072010

3

OPN RPN

136 81

20072010

3

OPN RPN

54 10

200320011

4

OPN RPN

153 31

20082010

4

OPN RPN

25 25

20092010

3

OPN RPN

133 145

RI PT

Lucas et al [2]

Comparison OPN vs RPN College of Medicine, retrospective Seoul National University Bundang Hospital, Seongnam, Korea James Buchanan Brady retrospective Urological Institute, Johns Hopkins University, Baltimore, MD Temple University prospective non School of Medicine, randomized Philadelphia, Pennsylvania, US Temple University prospective non School of Medicine, randomized Philadelphia, Pennsylvania, US University of California, retrospective san Diego, School of Medicine, La Jolla, California and University of Tennessee Helath Scince Center, Menphis Beth Irael Deaconess retrospective Medical Center, Boston, Massachusetts Glickman Urological and retrospective Clinical Institute , Cleveland Clinic,

period of surgery 20032010

SC

2011

Type of study

M AN U

Lee et al [1]

Institution

TE D

year

EP

Author, year

ACCEPTED MANUSCRIPT

3

OPN RPN

58 42

RI PT

2014

SC

Ficarra et al [9]

20082010

retrospective

M AN U

2013

Prospective non randomized

Retrospective

TE D

Mellon et al [8]

Cleveland, OH Department of Urology, Groupe HospitaloUniversitaire EST, PitiéSalpétrière Hospital, Assistance PubliqueHôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 1Department of Urology, University of Udine, Udine, 2Department of Urology, University of Florence, Florence, 3Department of Urology, University of Brescia, Brescia, Italy, 4Washington University School of Medicine, Saint Louis, MO, USA, 5Department of Urology, Vita-Salute University, San RaffaeleTurro Hospital, Milan, 6Department of Urology, University Federico II, Naples, 7Department of

EP

2012

AC C

Masson-Lecomte et al [7]

20032010

4

OPN RPN

54 27

20082010

4

OPN RPN

200 200

2014

Zagar et al (moderate) [13]

2014

SC

Wu et al [12]

20032013

4

OPN RPN

100 100

prospective non randomized

20102011

3

retrospective

20092013

4

OPN RPN OPN RPN

198 105 94 51

20072013

3

OPN RPN

33 30

M AN U

2013

retrospective

, Changhai Hospital, Second Military Medical University, Shanghai, P. R. China Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio. 2Washington University School of Medicine, Department of Urology, St. Louis, Missouri. 3James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland. 4New York University

TE D

Minervini et al [11]

EP

2014

AC C

Oh et al [10]

Urology, University of Bologna, Bologna, Italy, 8Luna Foundation, 9OLV Robotic Surgery Institute, Aalst, Belgium, 10Swedish Urology Group, Seattle,WA, USA, and 11Department of Urology, University of Padua, Padua, Italy Seul National University Budang Hospital, SeonGnam, Korea AGILE group

RI PT

ACCEPTED MANUSCRIPT

retrospective

Acar et al [14]

2015

Boylu et al [15]

2014

Mano et al [16]

2015

retrospective

20072013

3

OPN RPN

52 10

OPN RPN OPN RPN

74 59 20 46

OPN

190

SC

2014

AC C

EP

TE D

M AN U

Zagar et al(complex) [13]

School of Medicine, Department of Urology, New York, New York. 5Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio. 2Washington University School of Medicine, Department of Urology, St. Louis, Missouri. 3James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland. 4New York University School of Medicine, Department of Urology, New York, New York. 5Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan Koc University, Istanbul, Turkey

RI PT

ACCEPTED MANUSCRIPT

Umraniye Teaching Hospital, Istambul, Turkey Department of

retrospective

2010

3

prospective non randomized

20092013

3

retrospective

2011

3

ACCEPTED MANUSCRIPT

Mearini et al [19]

2015

Oh et al [20]

2016

Patton et al [21]

2015

Porpiglia et al [22]

2016

Record Project

63

RI PT

RPN

SC

M AN U

2015

retrospective

20122014

3

OPN RPN

15 16

retrospective

20072013

3

OPN RPN

289 114

prospective non randomized

20062015

3

OPN RPN

80 31

retrospective

20032015

4

OPN RPN

299 299

retrospective

19992013

4

Prospective non

2009-

3

OPN RPN OPN

37 90 133

TE D

Lee et al [18]

EP

2015

AC C

Miyake et al [17]

Surgery, Memorial Sloan Kettering Cancer Center b Department of Urology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea c Department of Urology, Seoul National University Bun-Dang Hospital, Seoul, South Korea Division of Urology, Kobe University Graduate School of Medicine,Chuo-ku, Kobe, Japan University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea Perugia Hospital, Sant' andrea delle Fratte, University of Perugia, Italy Seul National University Budang Hospital, SeonGnam, Korea Mayo Clinic, Phoenix, AZ, USA

ACCEPTED MANUSCRIPT

Department of Urology, Ain Shams University, Cairo, Egypt. An_han department of Urology, china

randomized retrospective

2012 20052011

4

2014

Hsieh et al [24]

2016

Peyronnet et al [25]

2016

France Multicentric

retrospective

Kara et al [26]

2016

Glickman Urological Institute , Cleveland

retrospective

20112016

4

Luciani et al [27]

2016

Trento Hospital

retrospective

20052016

4

Takagi et al [28]

2016

retrospective

20122014

4

Ramirez et al [29]

2016

Departmento of Urology, Tokio women medical university Cleveland Clinic

prpsèective

20112014

3

Wang et al [30]

2017

shanxi provincial people hospital, Taiyuan , China

retrospective

20072014

3

Malkoc et al [31]

2017

Cleveland Clinic

retrospective

20112015

3

Malkoc et al (>7 cm) [32]

2017

Cleveland Clinic

retrospective

20112015

3

Maurice et al (T1a) [33]

2017

Cleveland Clinic

retrospective

20092015

3

Maurice et al (T1b) [33]

2017

Cleveland Clinic

retrospective

20092015

3

Caruso et al [34]

2006

Cleveland Clinic

Comparison RPN vs LPN retrospective

20022004

4

M AN U

TE D

EP

AC C

20122014

4

20062014

4

SC

Retrospective

RI PT

Webb et al [23]

RPN OPN RPN

95 21 14

OPN RPN OPN RPN OPN RPN OPN RPN OPN RPN

35 45 863 937 56 87 73 110 48 48

OPN RPN OPN RPN OPN RPN OPN RPN OPN RPN OPN RPN

169 545 190 190 60 177 56 54 110 301 80 114

LPN RPN

10 10

ACCEPTED MANUSCRIPT

Jeong et al [38]

2009

Kural et al [39]

2009

Wang et al [40]

2009

Choi et al [41]

2010

DeLong et al [42]

2010

Haber et al [43]

2010

Cho et al [44]

2011

3

3

LPN RPN

11 12

20042008

3

LPN RPN

129 118

Retrospective

20062008

3

Istanbul Bilim University and Group Florence Nightingale Hospitals, Washington University, St Louis Missouri

Retrospective

20032009

3

LPN RPN LPN RPN

31 26 11 20

Retrospective

n/r

3

Samsung Medical Center, Sungkuyunkwan University School of Medicine, Seoul, Korea Lahey Clinic, Burligton, Massachusetts, USA ans Upstate Medical Syracuse NY, USA Cleveland Clinic, Cleveland, Ohio,

Prospective

20082009

2

LPN RPN LPN RPN

40 62 13 31

Retrospective

3 years

4

LPN RPN

13 15

Retrospective

20022009

3

University of Hong Kong, Queen Mary Hospital,

Retrospective

20082009

3

LPN RPN LPN RPN

75 75 10 10

RI PT

2009

12 12

20032007

SC

Benway et al [37]

LPN RPN

Retrospective

20062007

Retrospective

M AN U

2008

Retrospective

TE D

Deane et al [36]

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA Department of urology, university of ilinois at Chicago, University of California in Irvine California and University of Maryland, Maryland, University of Washington, NY center and Vatikuti Institute of Urology. Yonsei University, Seoul, Korea,

EP

2008

AC C

Aron et al [35]

ACCEPTED MANUSCRIPT

2011

Seo et al [48]

2011

Ellison et al [49]

2012

Lee et al [50]

2012

Hyams et al [51]

2012

Long et al [52]

2012

Lucas et al [2]

2012

Mullins et al [53]

2012

Alemozaffar et al

2013

2

The Mount Sinai Medical Center, New York, USA,

Retrospective

20052009

3

Brady Urological Institute, John Hopkins University, Baltimore, Maryland, Wonkwang University, Iksan, Korea

Retrospective

20062009

3

LPN RPN LPN RPN LPN RPN

18 32 20 18 48 102

LPN RPN LPN RPN

13 14 108 108

Retrospective

20092010

3

Retrospective

20072010

3

retrospective

20092012

4

LPN RPN

30 39

Retrospective

20092010

3

LPN RPN

20 20

Retrospective

20052011

3

LPN RPN

199 182

Retrospective

20032010

3

LPN RPN

27 15

Retrospective

20072011

3

LPN RPN

105 102

Retrospective

2008-

3

LPN

25

Department of Urology, University of Michigan, Ann Arbor, Michigan, Boston University medical center , Boston, Massachusietts Brady Urological Institute, John Hopkins University, Baltimore, Maryland, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA IN University School of Medicine, Indianapolis, IN, USA Brady Urological Institute, John Hopkins University, Baltimore, Maryland, Beth Deaconess Medical

AC C

RI PT

Pierorazio et al [47]

20012010

SC

2011

Prospective

M AN U

Lavery et al [46]

Hong Kong Cleveland Clinic, Cleveland, Ohio,

TE D

2011

EP

Hillyer et al [45]

ACCEPTED MANUSCRIPT

Laydner et al [6]

2013

Liu et al [57]

2013

Masson- Lecomte et al [58]

2012

Panumartrassamee 2012 et al [59]

Williams et al [60]

2013

Faria et al [61]

2014

3

LPN RPN

19 43

20022012

3

LPN RPN

261 235

retrospective

20092010

3

LPN RPN

145 47

retrospective

20032011

3

LPN RPN

53 126

retrospective

20072011

3

retrospective

20002012

3

LPN RPN LPN RPN

220 45 15 52

prospective

20062010

2

LPN RPN

27 59

retrospective

2008-

3

LPN

137

Retrospective

Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio Brigham and Women’s Hospital, Harvard Medical School, boston Department of Urology,

3

RI PT

2013

25 48 52

20062010

SC

Khalifeh et al [56]

RPN LPN RPN

retrospective

M AN U

2013

2010 20072010

Retrospective

TE D

Elsamra et al [55]

Center, Boston, KEPCO Medical Center, Seoul- Kyung Hee University School of Medicine, Samsung Medical Center, The warren Alpert Medical School of Brown University, Providence, Rhode Island Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH Cancer Center, Sun Yeatsen University, Guangzhou People's Republic of China French Multicenter study

EP

2013

AC C

[5] Choi et al [54]

ACCEPTED MANUSCRIPT

Unit 1373, University of Texas Georgetown University Hospital

2012 retrospective

20072011

3

20072013

3

20092012

2

2014

Jang et al [63]

2014

Samsung Medical Center, Seu Korea

retrospective

Vasdev et al [64]

2014

prospective

Dar et al [65]

2015

Hertdfordshire and south Bedfordshire Robotic Urological Cancer Centre , Lister Hospital, Stevenage, UK Sir Ganga Ram Hospital, New Delhi, India

retrospective

6 years

4

Hanzly et al [66]

2014

Roswell Park Cancer Institute, Buffalo, NY

retrospective

n/a

4

Kim et al [67]

2015

Multicenter Korean Group

retrospective

20032011

3

Ricciardulli et al [68]

2014

retrospective

20142012

3

Webb et al [23]

2014

Tapei Veterans General Hospital, Tapei, Taiwan, ROC Ain Shams University, Cairo

retrospective

20052011

3

Wu et al[69]

2014

Changai Hospital

retrospective

20092013

3

Zagar et al [70]

2014

retrospective

20042013

3

SC

M AN U

TE D

EP

AC C

RI PT

Harbin et al [62]

Cleveland Clinic, Glickman Urological and Kidney Institute, Cleveland, OH, †The Johns Hopkins Medical Institutions, James Buchanan Brady Urological Institute,

RPN

146

LPN RPN LPN RPN LPN RPN

31 77 89 38 50 50

LPN RPN LPN RPN LPN RPN LPN RPN

16 17 116 116 195 195 58 58

LPN RPN LPN RPN LPN RPN

14 31 77 77 1185 646

SC

BalJmore, MD, ‡Dept, of Urology, Washington University School of Medicine, St, Louis, MO, §Dept, of Urology, New York University School of Medicine, New York, NY, and ¶Henry Ford Health System, Vattikuti Urology Institute, Detroit, MI, USA Perugia Hospital Sant' Retrospective andrea delle Fratte

RI PT

ACCEPTED MANUSCRIPT

19992015

3

20082014

3

20062014 20082014

4

Retrospective

20092012

Retrospective

Retrospective

2015

Wang et al [71]

2015

Chinese Peoples Liberation Army Hospital

Retrospective

Andrade et al [72]

2016

Cleveland Clinic

Retrospective

Carniero et al [73]

2015

Porpiglia et al [22]

2016

Ganpule et al [74]

2015

Stroup et al [4]

2012

Institute Mutualiste Montsouris paris Cedex, France Univeristy of Turin, Univeristy of Florence, University of Modena, University of Padua,. Muljbhai Patel Urological Institute Hospital Dr Virendra Desai San Diego School of Medicine. Naval Medical Center of San Diego. Uniersity of Tennessee Health Science Center.

M AN U

Mearini et al [19]

AC C

EP

TE D

retrospectively

LPN RPN LPN RPN LPN RPN LPN RPN

31 66 81 135 52 52 44 152

3

LPN RPN

95 57

20102013

4

LPN RPN

58 15

20032011

3

LPN RPN

31 100

4

ACCEPTED MANUSCRIPT

2015

Mayo Clinic

retrospective

19992013

3

Luciani et al [27]

2016

Santa Chiara Hospital, Trento Italy

prospective

20052016

3

Hsiesh et al [24]

2016

An_han department od Urology, china

Retrospective

20122014

4

20112013

90 55 110 70 35 26

3

TP-RPN RP-RPN

16 10

n/a

3

TP-RPN RP-RPN

59 44

retrospective

20082012

3

retrospective

20072014

3

TP-RPN RP-RPN TP-RPN RP-RPN

57 50 97 116

SC

prospective

retrospective

AC C

EP

TE D

M AN U

Comparison transperitoneal vs retroperitoneal RPN Tanaka et al [75] 2013 Kobe University Graduate School of Medicine Hughes-Hallet et al 2013 Department of Surgery [76] and Cancer, Imperial College, London, United Kingdom. 2Urology Department, Barts and The London Hospitals, London, United Kingdom . 3Urology Department, Oxford University Hospitals, Oxford, United Kingdom. 4Urology Department, rimley Park Hospital, Frimley, United Kingdom. 5Urology Department, Broomfield Hospital, Chelmsford, United Kingdom. Choo et al [77] 2014 Samsung Medical Center

LPN RPN LPN RPN LPN RPN

RI PT

Patton et al [21]

Kim et al [78]

2015

Washington University School of Medicine

ACCEPTED MANUSCRIPT

2017

multicenter

20072015

3

TP-RPN RP-RPN

296 74

prospective

2008

3

20092010

3

20082011

4

20072011

3

prospective

20102011

3

retrospective

20102013

4

retrospective

20082012

4

RPN off clamp RPN on-clamp RPN off clamp RPN on-clamp RPN off clamp RPN on-clamp RPN off clamp RPN on-clamp RPN off clamp RPN on-clamp RPN off clamp RPN on-clamp RPN off clamp RPN on-clamp RPN off clamp RPN on-clamp RPN off clamp RPN on-clamp

8 20 22 35 29 29 49 283 18 19 30 14 40 33 23 114 26 104

RPN Selective Clamp RPN on-clamp RPN Selective Clamp RPN on-clamp RPN Selective Clamp

25

2012

Arthur G James Cancer Hospital

prospective

Tanagho et al [82]

2012

Washington University

Retrospective

Kaczmarek et al [83]

2012

Henry Ford Hospital

prospective

Krane et al [84]

2013

Wake Forest University

Acar et al [85]

2014

VFK American Hospital, Koc

Comez et al [86]

2016

Dokuz Eylul University

Komninos et al [87]

2014

Yonsei University College of Medicine

retrospective

20072013

4

Peyronnet et al [88]

2017

Multi-Center France

retrospedtive

20102014

4

retrospective

20072013

3

2016

Paulucci et al [90]

2017

M AN U

TE D

AC C

Comparison off clamp RPN vs clamp RPN Komninos et al [87] 2014 Yonsei University College of Medicine Furukawa et al [89]

SC

Novak et al [81]

EP

Comparison off clamp RPN vs clamp RPN White et al [80] 2009 Cleveland Clinic

retrospective

RI PT

Maurice et al [79]

Kobe University retrospective Graduate School of Medicine Icahn School of Medicine prospective at Mount Sinai Hospital,

20122013

3

20082015

2

114 19 20 66

McClintock et al [93] Desai et al [94]

2014

2014

USC Insitute of Urology

SC

2011

retrospective

prospective

prospective

retrospective

20092013 20112012 20092012 20092012

3

3

3

3

3

EP

Hallym Medical College, Changi General Hospital, General Hospital of Nikaia, Yonsei University College of Medicine Comparison early unclamp RPN vs clamp RPN Peyronnnet, 2014 2014 Saint-Joseph Hospital, La [96] Pitié-Salpétrière Hospital, Henri-Mondar Hospital, University of Bordeaux, University of Toulouse, University of Nimes, University of 2015

AC C

Shin et al [95]

2014

prospective

M AN U

Harke et al [92]

2013

TE D

Borofsky et al [91]

Yale New Haven Hospital, Ohio Health Dublin Methodist Hospital, Temple University School of Medicine, Wake Forest School of Medicine New York University, USC Institute of Urology, Wake Forest Baptist Medical Center Missionsaerztliche Klinkik, University Medical Center New York University

RI PT

ACCEPTED MANUSCRIPT

retrospective

20092013

4

RPN on-clamp

132

RPN Super Selective Clamp RPN on clamp

27

RPN Super Selective Clamp RPN on-clamp RPN Super Selective Clamp RPN on clamp RPN Super Selective RPN on-clamp RPN Super Selective Clamp RPN on-clamp

15

RPN earlyunclamp RPN on-clamp

222

27

15 42 42 58 63 20 97

208

ACCEPTED MANUSCRIPT

8. 9. 10. 11. 12. 13. 14. 15.

20132014

SC

M AN U

7.

TE D

5. 6.

retrospective

5

RPN earlyunclamp RPN on-clamp

61 35

Lee, S., et al., Open versus robot-assisted partial nephrectomy: effect on clinical outcome. J Endourol, 2011. 25(7): p. 1181-5. Lucas, S.M., et al., A comparison of robotic, laparoscopic and open partial nephrectomy. Jsls, 2012. 16(4): p. 581-7. Simhan, J., et al., Perioperative outcomes of robotic and open partial nephrectomy for moderately and highly complex renal lesions. J Urol, 2012. 187(6): p. 2000-4. Stroup, S.P., et al., RENAL nephrometry score is associated with operative approach for partial nephrectomy and urine leak. Urology, 2012. 80(1): p. 151-6. Alemozaffar, M., et al., Comparing costs of robotic, laparoscopic, and open partial nephrectomy. J Endourol, 2013. 27(5): p. 560-5. Laydner, H., et al., Single institutional cost analysis of 325 robotic, laparoscopic, and open partial nephrectomies. Urology, 2013. 81(3): p. 533-8. Masson-Lecomte, A., et al., A prospective comparison of the pathologic and surgical outcomes obtained after elective treatment of renal cell carcinoma by open or robot-assisted partial nephrectomy. Urol Oncol, 2013. 31(6): p. 924-9. Mellon, M.J., et al., A comparison of pathologic outcomes of matched robotic and open partial nephrectomies. Int Urol Nephrol, 2013. 45(2): p. 381-5. Ficarra, V., et al., A multicentre matched-pair analysis comparing robot-assisted versus open partial nephrectomy. BJU Int, 2014. 113(6): p. 936-41. Oh, J.J., et al., Comparison of robotic and open partial nephrectomy: Single-surgeon matched cohort study. Journal of the Canadian Urological Association, 2014. 8(7-8). Minervini, A., et al., Open versus robotic-assisted partial nephrectomy: a multicenter comparison study of perioperative results and complications. World J Urol, 2014. 32(1): p. 287-93. Wu, Z., et al., A propensity-score matched comparison of perioperative and early renal functional outcomes of robotic versus open partial nephrectomy. PLoS One, 2014. 9(4): p. e94195. Zargar, H., et al., Comparison of perioperative outcomes of robot-assisted partial nephrectomy and open partial nephrectomy in patients with a solitary kidney. J Endourol, 2014. 28(10): p. 1224-30. Acar, O., et al., Comparison of the trifecta outcomes of robotic and open nephron-sparing surgeries performed in the robotic era of a single institution. Springerplus, 2015. 4. Boylu, U., et al., Comparison of surgical, functional, and oncological outcomes of open and robot-assisted partial nephrectomy. Journal of Minimal Access Surgery, 2015. 11(1): p. 72-77.

EP

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Tours Tokyo Women's Medical University

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1. 2. 3.

2015

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Kondo, 2015[97]

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29. 30. 31. 32.

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20.

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19.

TE D

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Acar, O., et al., Do We Need to Clamp the Renal Hilum Liberally during the Initial Phase of the Learning Curve of Robot-Assisted NephronSparing Surgery? Scientific World Journal, 2014. Comez, K., et al., Partial Nephrectomy for Stage I Renal Cell Carcinoma: On-clamp or Off-clamp? Journal of Urological Surgery, 2016. 3(2): p. 38-41. Komninos, C., et al., Renal function is the same 6 months after robot-assisted partial nephrectomy regardless of clamp technique: analysis of outcomes for off-clamp, selective arterial clamp and main artery clamp techniques, with a minimum follow-up of 1 year. BJU Int, 2015. 115(6): p. 921-8. Peyronnet, B., et al., Early unclamping technique during robot-assisted laparoscopic partial nephrectomy can minimise warm ischaemia without increasing morbidity. BJU Int, 2014. 114(5): p. 741-7. Furukawa, J., et al., Renal Functional and Perioperative Outcomes of Selective Versus Complete Renal Arterial Clamping During RobotAssisted Partial Nephrectomy: Early Single-Center Experience With 39 Cases. Surgical Innovation, 2016. 23(3): p. 242-248. Paulucci, D.J., et al., Selective arterial clamping does not improve outcomes in robot-assisted partial nephrectomy: a propensity-score analysis of patients without impaired renal function. BJU Int, 2017. 119(3): p. 430-435. Borofsky, M.S., et al., Near-infrared fluorescence imaging to facilitate super-selective arterial clamping during zero-ischaemia robotic partial nephrectomy. BJU Int, 2013. 111(4): p. 604-10. Harke, N., et al., Selective clamping under the usage of near-infrared fluorescence imaging with indocyanine green in robot-assisted partial nephrectomy: a single-surgeon matched-pair study. World J Urol, 2014. 32(5): p. 1259-65. McClintock, T.R., et al., Can selective arterial clamping with fluorescence imaging preserve kidney function during robotic partial nephrectomy? Urology, 2014. 84(2): p. 327-32. Desai, M.M., et al., Robotic Partial Nephrectomy with Superselective Versus Main Artery Clamping: A Retrospective Comparison. European Urology, 2014. 66(4): p. 713-719. Shin, T.Y., et al., Clinical values of selective-clamp technique in robotic partial nephrectomy. World J Urol, 2015. 33(6): p. 763-9. Peyronnet, B., et al., Off-Clamp versus On-Clamp Robotic Partial Nephrectomy: A Multicenter Match-Paired Case-Control Study. Urol Int, 2017. Kondo, T., et al., Early unclamping might reduce the risk of renal artery pseudoaneurysm after robot-assisted laparoscopic partial nephrectomy. Int J Urol, 2015. 22(12): p. 1096-102.

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ACCEPTED MANUSCRIPT

Heterogeneity

Total n. of patients (OPN /RPN)

n. of studies

X²

df

I²

p-value

OR/WMD (95% CI)

p-value

0.91

Open PN vs Robotic PN 27

3989/3441

1644

26

98%

<0.00001

-0.19 [-3.54, 3.16]

Sex, Male

29

3181/2802

125.2

28

78%

<0.00001

1.00 [0.78, 1.27]

0.98

Sex, Female

29

3919/3713

143.4

28

80%

<0.00001

1.08 [0.84, 1.40]

0.52

BMI

24

3510/3417

93.91

23

76%

<0.00001

-0.30 [-0.71, 0.11]

0.15

ASA score

9

903/780

4.12

7

0%

0.77

0.07 [-0.02, 0.17]

0.15

Preoperative GFR

20

3064/3241

34.25

19

45

0.02

-0.76 [-2.04, 0.52]

0.25

Tumor Size

25

3694/3619

348.7

24

93%

<0.00001

0.36 [0.19, 0.54]

<0.0001

RENAL score

13

982/2510

161.8

12

93%

RENAL score (low)

10

982/759

11.51

9

22%

RENAL score (moderate)

10

919/835

25.5

9

65%

RENAL score (high)

10

810/867

Tumor side, Left

12

1563/1100

Tumor side, Right

12

1563/1100 2380/2154

11

2039/1850

pT2

13

2039/1850

pT3a

11

2345/2109

pT3b

2

917/961

SC

0.19 [-0.04, 0.42]

0.10

0.24

-0.06 [-0.10, -0.01]

0.0009

0.002

0.86 [0.71, 1.05]

0.14

M AN U

12

pT1b

<0.00001

11.87

9

24%

0.22

0.87 [0.67, 1.13]

0.3

13.21

11

17%

0.28

1.04 [0.89, 1.22]

0.62

13.21

11

17%

0.28

1.04 [0.89, 1.22]

0.62

56.51

11

81%

<0.00001

0.93 [0.63, 1.37]

0.72

15.95

10

37%

0.1

1.01 [0.85, 1.20]

0.93

15.95

10

37%

0.1

1.01 [0.85, 1.20]

0.93

12.76

9

29%

0.17

1.27 [0.90, 1.78]

0.18

3.22

1

69%

0.07

2.15 [0.35, 12.32]

0.41

TE D

pT1a

RI PT

Age

AC C

EP

Table 1 Summary table of baseline characteristic meta-analysis of studies comparing open partial nephrectomy (OPN) vs robotic partial nephrectomy (RPN). X²= Chi-square; df= degree of freedom; CI = confidence interval; WMD = weighted mean difference: OR = odds ratio.

ACCEPTED MANUSCRIPT

Heterogeneity

Total n. of patients (LPN /RPN)

n. of studies

OR/WMD (95% CI) X²

df

I²

p-value

p-value

26

2110/2040

51.55

25

52%

0.001

Sex, Male

34

2989/3426

55.25

33

40%

0.009

Sex, Female

34

2898/3426

77.41

33

57%

<0.0001

BMI

27

2112/2061

76.6

26

66%

<0.00001

ASA score

11

527/645

26.85

10

63%

0.003

Preoperative GFR

20

1935/1935

146.52

19

87%

PADUA score

3

201/166

3.48

2

42%

RENAL score

11

1048/950

69.19

10

86%

RENAL score (low)

10

710/900

RENAL score (moderate)

11

845/981

RENAL score (high)

11

845/981

Tumor Right Side

26

1894/1662

Tumor Left Side

26

1894/1663

pT1a

15

960/1102

pT1b

14

pT2

12

pT3a

8

pT3b

4

-0.75 [-1.9, 0.4]

0.20

1.02 [0.99, 1.08]

0.58

1.00 [0.82, 1.21]

0.98

0.3 [-0.20, 0.8]

0.24

-0.01 [-0.14, 0.11]

0.82

SC

Age

RI PT

Laparoscopic PN vs Robotic PN

-2.63 [-5.84, 0.58]

0.11

0.18

-0.12 [-0.39, 0.16]

0.4

<0.00001

-0.33 [-0.65, -0.00]

0.05

M AN U

<0.00001

9

71%

0.0003

1.56 [1.01, 2.41]

0.04

20.12

10

50%

0.03

0.88 [ 0.65, 1.21]

0.44

3.81

8

0%

0.87

0.64 [0.43, 0.98]

0.04

20.02

25

0%

0.75

0.96 [0.84, 1.10]

0.6

47.88

25

48%

0.004

1.11 [0.97, 1.27]

0.13

43.46

14

68%

<0.0001

0.85 [0.56, 1.3]

0.46

910/1062

30.95

13

58%

0.003

0.87 [0.55, 1.38]

0.57

811/806

4.52

9

0%

0.87

0.88 [ 0.46, 1.65]

0.68

713/653

4.73

6

0%

0.58

0.63 [ 0.39, 1.03]

0.07

465/485

-

-

-

-

3.03[0.12, 75.16]

0.5

EP

TE D

30.89

AC C

Table 2. Summary table of baseline characterstic meta-analysis of studies comparing laparoscopic partial nephrectomy (LPN) vs robotic partial nephrectomy (RPN). X²= Chi-square; df= degree of freedom; CI = confidence interval; WMD = weighted mean difference: OR = odds ratio.

ACCEPTED MANUSCRIPT

Heterogeneity

Total n. of patients (TP-RPN/RP-RPN)

OR/WMD (95% CI) X²

df

I²

p-value

TRANSPERITONEAL RPN vs RETROPERITONEAL RPN

p-value

RI PT

n. of studies

3

412/168

2.18

2

8%

0.34

Sex, Male

3

369/134

0.01

2

0%

1

Sex, Female

3

369/134

0.01

2

0%

1

BMI

3

369/134

0.94

2

0%

0.44

ASA score

2

353/124

4.89

1

80%

0.03

0.15 [-0.16, 0.45]

0.35

Preoperative GFR

2

312/84

1.54

1

35%

0.22

-3.55 [-9.48, 2.39]

0.24

Tumor Size

4

428/178

10.91

3

73%

0.01

0.30 [-0.11, 0.72]

0.15

Anterior

4

428/178

8.14

2

75%

0.02

2.64 [0.47, 14.85]

0.27

Posterior

4

428/178

11.13

2

82%

0.03

0.05 [0.00, 0.72]

0.03

PADUA score

1

16/10

-

-

-

-

0.40 [-0.61, 1.41]

0.44

RENAL score

4

428/178

8.87

3

66%

0.03

0.03 [-0.56, 0.61]

0.93

Tumor side, Left

4

428/178

1.89

3

0%

0.60

1.18 [0.82, 1.70]

0.37

Tumor side, Right

4

428/178

2.82

3

0%

0.42

0.74 [0.51, 1.06]

0.1

pT1a

2

353/124

0.45

1

0%

0.5

1.14 [0.69, 1.88]

0.62

pT1b

1

57/50

-

-

-

-

0.27 [0.05, 1.39]

0.12

M AN U

TE D

-0.05 [-2.13, 2.03]

0.96

0.59 [0.38, 0.92]

0.02

1.69 [1.09, 2.63]

0.02

-0.32 [-1.14, 0.49]

0.44

SC

Age

AC C

EP

Table 3. Summary table of baseline characterstic analysis of studies comparing transperitoneal partial nephrectomy (TP-PN) vs retroperitoneal partial nephrectomy (RP-PN). X²= Chi-square; df= degree of freedom; CI = confidence interval; WMD = weighted mean difference: OR = odds ratio

ACCEPTED MANUSCRIPT

Outcomes

n. of studies

Heterogeneity

Total n. of patients (experimental /control)

X²

df

I²

p-value

OR/WMD (95% CI)

p-value

7

215/596

39.99

6

85%

<0.00001

0.68 [-2.22, 3.58]

0.65

Sex, male

4

120/430

2.82

3

0%

0.42

0.94 [0.60, 1.48]

0.80

Sex female

4

120/430

2.82

3

0%

0.42

1.06 [0.68, 1.66]

0.80

BMI, Kg/m²

5

145/549

6.05

4

34%

0.20

-0.15 [-0.40, 0.09]

0.22

ASA score

4

134/430

2.46

3

0%

0.48

0.01 [-0.12, 0.14]

0.87

Preoperative eGFR

8

238/623

42.37

7

83%

<0.00001

1.39 [-4.19, 6.97]

0.63

R.E.N.A.L score

6

197/577

20.29

5

75%

0.001

-0.29 [-0.57, -0.01]

0.04

PADUA score

2

53/128

2.33

1

57%

0.13

-1.30 [-1.78, -0.81]

<0.00001

Tumor size

6

170/329

45.017

5

89%

<0.00001

-0.43 [-1.47, 0.60]

0.48

Exophitic

1

23/114

Endophitic

2

41/133

pT1a

4

97/159

pT1b

4

97/159

pT2

3

76/136

pT3

-

-

SC

Age

M AN U

RI PT

OffOff-clamp RPN vs OnOn-clamp RPN

-

-

-

-

9.56 [3.51, 26.05]

<0.0001

5.07

1

80%

0.02

0.23 [0.01, 7.34]

0.40

5.27

3

43%

0.15

1.29 [0.65, 2.53]

0.46

2.41

3

0%

0.49

0.51 [0.23, 1.10]

0.08

1.29

2

0%

0.52

1.91 [0.47, 7.74]

0.36

-

-

-

-

-

-

AC C

EP

TE D

Table 4. Summary table of baseline characterstic analysis of studies comparing Off-clamp RPN vs On-clamp RPN. X²= Chisquare; df= degree of freedom; CI = confidence interval; WMD = weighted mean difference: OR = odds ratio

ACCEPTED MANUSCRIPT

Outcomes

n. of studies

Total n. of patients (experimental /control)

Heterogeneity OR/WMD (95% CI) X²

df

I²

p-value

p-value

RI PT

Selective/SuperSelective/Super-selective RPN vs OnOn-clamp RPN 5

164/336

1.88

4

0%

0.76

Sex, male

5

102/159

1.99

4

0%

0.74

-1.23 [-3.92, 1.45]

0.43

1.22 [0.82, 1.83]

0.32

Sex female

5

172/343

1.99

4

0%

0.32

0.82 [0.55, 1.22]

0.32

BMI, Kg/m²

5

164/336

3.56

4

0%

0.47

ASA score

3

120/202

1.68

2

0%

0.43

0.65 [-0.19, 1.49]

0.13

0.07 [-0.07, 0.20]

0.33

Preoperative eGFR

5

230/468

1.55

4

0%

0.72

-1.99 [-5.91, 1.93]

0.32

R.E.N.A.L score

6

147/363

12.37

5

60%

PADUA score

2

83/177

2.95

1

66%

0.03

-0.04 [-0.51, 00.42]

0.74

0.09

0.94 [-0.21, 1.66]

0.01

Tumor size

5

164/336

18.81

4

79%

0.0009

0.04 [-0.54, 0.63]

0.88

Exophitic

1

25/114

-

-

-

-

2.79 [1.10, 7.03]

0.03

Endophitic

1

25/114

-

-

-

-

0.46 [0.16, 1.33]

0.15

pT1a

4

108/265

1.45

3

0%

0.69

0.65 [0.40, 1.06]

0.25

pT1b

4

108/265

0.92

3

0%

0.82

1.73 [1.00, 3.01]

0.05

pT2

4

108/265

1.14

2

0%

0.57

0.74 [0.16, 3.35]

0.69

pT3

4

108/265

0.06

1

0%

0.81

1.71 [0.20, 14.50]

0.62

M AN U

SC

Age

AC C

EP

TE D

Table 5. Summary table of baseline characterstic analysis of studies comparing Selective/Superselective RPN vs On-clamp RPN. X²= Chi-square; df= degree of freedom; CI = confidence interval; WMD = weighted mean difference: OR = odds ratio

ACCEPTED MANUSCRIPT

ROBOTIC VS OPEN

M AN U

SC

RI PT

PARTIAL NEPHRECTOMY META-ANALYSES

1) Cumulative meta-analysis of studies reporting baseline characteristics 2) Cumulative meta-analysis of studies reporting perioperative outcomes 3) Sensitivity meta-analysis of studies reporting % eGFR change

TE D

4) Sensitivity meta-analysis of perioperative outcomes in studies reporting R.E.N.A.L score in mean/median and SD/range

5) Sensitivity meta-analysis of perioperative outcomes in studies reporting similar (p value > 0.05) R.E.N.A.L score

EP

6) Sensitivity meta-analysis of perioperative outcomes in studies reporting > 70 procedures:

AC C

7) Sensitivity meta-analysis of studies reporting complex renal masses

1|P age

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

1) Cumulative meta-analysis of studies reporting baseline characteristics

2|P age

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

a) Age

3|P age

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

b) Gender male rate

4|P age

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

c) Gender female rate

5|P age

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

d) BMI

6|P age

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

e) ASA

7|P age

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Preoperative eGFR

AC C

f)

8|P age

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

g) Tumor size

9|P age

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

h) T1a rate

10 | P a g e

EP

TE D

M AN U

SC

T1b rate

AC C

i)

RI PT

ACCEPTED MANUSCRIPT

11 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

T2 rate

AC C

j)

12 | P a g e

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

k) T3a rate

13 | P a g e

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

a) Right side tumor rate

14 | P a g e

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

b) Left side tumor rate

15 | P a g e

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

c) Mean R.E.N.A.L score

16 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

d) Low R.E.N.A.L score, rate

17 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

e) Intermediate R.E.N.A.L score, rate

18 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

High R.E.N.A.L score, rate

AC C

f)

19 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

2) Cumulative meta-analysis of studies reporting perioperative outcomes

20 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

a) Operative time, min

21 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

b) Estimated blood loss, ml

22 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

c) Warm Ischemia time, min

23 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

d) Conversion to radical nephrectomy rate

24 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

e) Transfusions rate

25 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Overall intraoperative complications rate

AC C

f)

26 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall postoperative complications rate

27 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

h) Clavien-Dindo < 3 complication rate

28 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo ≥ 3 complications rate

AC C

i)

29 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Length of hospital stay, days

AC C

j)

30 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

k) Readmission rate

31 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Latest postoperative % eGFR change

AC C

l)

32 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

m) Positive margins rate

33 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

n) Overall mortality rate

34 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

o) Cancer specific mortality

35 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

p) Recurrence rate

36 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

3) Sensitivity meta-analysis of studies reporting % eGFR change

37 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

a) Mean R.E.N.A.L score

38 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

b) Mean Tumor size, cm

39 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

c) Warm Ischemia Time, min

40 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

d) Mean % eGFR decrease

41 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

4) Sensitivity meta-analysis of perioperative outcomes in studies reporting R.E.N.A.L score in mean/median and SD/range

42 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

a) Studies reporting mean/median R.E.N.A.L. score

43 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

b) Operative time, min

44 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

c) Estimated blood loss, ml

45 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

d) Warm Ischemia time, min

46 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

e) Conversion to radical nephrectomy rate

47 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Transfusions rate

AC C

f)

48 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall intraoperative complications rate

49 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

h) Overall postoperative complications rate

50 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo < 3 complication rate

AC C

i)

51 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo ≥ 3 complications rate

AC C

j)

52 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

k) Length of hospital stay, days

53 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Readmission rate

AC C

l)

54 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

m) Latest postoperative % eGFR change

55 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

n) Positive margins rate

56 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

o) Overall mortality rate

57 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

p) Cancer specific mortality

58 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

q) Recurrence rate

59 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

5) Sensitivity meta-analysis of perioperative outcomes in studies reporting similar (p value > 0.05) R.E.N.A.L score

60 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

a) Analysis of mean RENAL score when reported similar between the 2 groups

61 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

b) Operative time, min

62 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

c) Estimated blood loss, ml

63 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

d) Warm Ischemia time, min

64 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

e) Conversion to radical nephrectomy rate

65 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Transfusions rate

AC C

f)

66 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall intraoperative complications rate

67 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

h) Overall postoperative complications rate

68 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo < 3 complication rate

AC C

i)

69 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo ≥ 3 complications rate

AC C

j)

70 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

k) Length of hospital stay, days

71 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Readmission rate

AC C

l)

72 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

m) Latest postoperative % eGFR change

73 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

n) Positive margins rate

74 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

o) Cancer specific mortality

75 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

p) Recurrence rate

76 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

6) Sensitivity meta-analysis of perioperative outcomes in studies reporting > 70 procedures

77 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

a) Operative time, min

78 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

b) Estimated blood loss, ml

79 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

c) Warm Ischemia time, min

80 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

d) Conversion to radical nephrectomy rate

81 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

e) Transfusions rate

82 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Overall intraoperative complications rate

AC C

f)

83 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall postoperative complications rate

84 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

h) Clavien-Dindo < 3 complication rate

85 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo ≥ 3 complications rate

AC C

i)

86 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Length of hospital stay, days

AC C

j)

87 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

k) Readmission rate

88 | P a g e

ACCEPTED MANUSCRIPT

EP

TE D

M AN U

SC

RI PT

Latest postoperative % eGFR change

AC C

l)

89 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

m) Positive margins rate

90 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

n) Overall mortality rate

91 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

o) Cancer specific mortality

92 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

p) Recurrence rate

93 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

7) Sensitivity meta-analysis of studies reporting complex renal masses

94 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

a) Operative time, min

95 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

b) Estimated blood loss, ml

96 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

c) Warm Ischemia time, min

97 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

d) Conversion to radical nephrectomy rate

98 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

e) Transfusions rate

99 | P a g e

ACCEPTED MANUSCRIPT

Overall intraoperative complications rate

AC C

EP

TE D

M AN U

SC

RI PT

f)

100 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall postoperative complications rate

101 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

h) Clavien-Dindo < 3 complication rate

102 | P a g e

ACCEPTED MANUSCRIPT

Clavien-Dindo ≥ 3 complications rate

AC C

EP

TE D

M AN U

SC

RI PT

i)

103 | P a g e

ACCEPTED MANUSCRIPT

Length of hospital stay, days

AC C

EP

TE D

M AN U

SC

RI PT

j)

104 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

k) Readmission rate

105 | P a g e

ACCEPTED MANUSCRIPT

Latest postoperative % eGFR change

AC C

EP

TE D

M AN U

SC

RI PT

l)

106 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

m) Positive margins rate

107 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

n) Overall mortality rate

108 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

o) Cancer specific mortality

109 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

p) Recurrence rate

110 | P a g e

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

111 | P a g e

ACCEPTED MANUSCRIPT P age |1

M AN U

SC

META-ANALYSES

RI PT

ROBOTIC VS LAPAROSCOPIC PARTIAL NEPHRECTOMY

1) Cumulative meta-analysis of studies reporting baseline characteristics 2) Cumulative meta-analysis of studies reporting perioperative outcomes 3) Sensitivity meta-analysis of perioperative outcomes in studies reporting > 70 procedures:

AC C

EP

TE D

4) Sensitivity meta-analysis of studies reporting complex renal masses

1|P age

ACCEPTED MANUSCRIPT P age |2

AC C

EP

TE D

M AN U

SC

RI PT

1) Cumulative meta-analysis of studies reporting baseline characteristics

2|P age

ACCEPTED MANUSCRIPT P age |3

AC C

EP

TE D

M AN U

SC

RI PT

a) Age

3|P age

ACCEPTED MANUSCRIPT P age |4

AC C

EP

TE D

M AN U

SC

RI PT

b) Gender male rate

4|P age

ACCEPTED MANUSCRIPT P age |5

AC C

EP

TE D

M AN U

SC

RI PT

c) Gender female rate

5|P age

ACCEPTED MANUSCRIPT P age |6

AC C

EP

TE D

M AN U

SC

RI PT

d) BMI

6|P age

ACCEPTED MANUSCRIPT P age |7

AC C

EP

TE D

M AN U

SC

RI PT

e) ASA

7|P age

ACCEPTED MANUSCRIPT P age |8

EP

TE D

M AN U

SC

RI PT

Preoperative eGFR

AC C

f)

8|P age

ACCEPTED MANUSCRIPT P age |9

AC C

EP

TE D

M AN U

SC

RI PT

g) Tumor size

9|P age

ACCEPTED MANUSCRIPT P a g e | 10

AC C

EP

TE D

M AN U

SC

RI PT

h) T1a rate

10 | P a g e

ACCEPTED MANUSCRIPT P a g e | 11

EP

TE D

M AN U

SC

RI PT

T1b rate

AC C

i)

11 | P a g e

ACCEPTED MANUSCRIPT P a g e | 12

EP

TE D

M AN U

SC

RI PT

T2 rate

AC C

j)

12 | P a g e

ACCEPTED MANUSCRIPT P a g e | 13

AC C

EP

TE D

M AN U

SC

RI PT

k) T3a rate

13 | P a g e

ACCEPTED MANUSCRIPT P a g e | 14

EP

TE D

M AN U

SC

RI PT

T3b rate

AC C

l)

14 | P a g e

ACCEPTED MANUSCRIPT P a g e | 15

AC C

EP

TE D

M AN U

SC

RI PT

m) Right side tumor rate

15 | P a g e

ACCEPTED MANUSCRIPT P a g e | 16

AC C

EP

TE D

M AN U

SC

RI PT

n) Left side tumor rate

16 | P a g e

ACCEPTED MANUSCRIPT P a g e | 17

AC C

EP

TE D

M AN U

SC

RI PT

o) Mean R.E.N.A.L score

17 | P a g e

ACCEPTED MANUSCRIPT P a g e | 18

AC C

EP

TE D

M AN U

SC

RI PT

p) Mean PADUA score

18 | P a g e

ACCEPTED MANUSCRIPT P a g e | 19

AC C

EP

TE D

M AN U

SC

RI PT

q) Low R.E.N.A.L score, rate

19 | P a g e

ACCEPTED MANUSCRIPT P a g e | 20

AC C

EP

TE D

M AN U

SC

RI PT

r) Intermediate R.E.N.A.L score, rate

20 | P a g e

ACCEPTED MANUSCRIPT P a g e | 21

AC C

EP

TE D

M AN U

SC

RI PT

s) High R.E.N.A.L score, rate

21 | P a g e

ACCEPTED MANUSCRIPT P a g e | 22

AC C

EP

TE D

M AN U

SC

RI PT

t) Upper pole rate

22 | P a g e

ACCEPTED MANUSCRIPT P a g e | 23

AC C

EP

TE D

M AN U

SC

RI PT

u) Mid pole rate

23 | P a g e

ACCEPTED MANUSCRIPT P a g e | 24

AC C

EP

TE D

M AN U

SC

RI PT

v) Lower pole rate

24 | P a g e

ACCEPTED MANUSCRIPT P a g e | 25

AC C

EP

TE D

M AN U

SC

RI PT

w) Hilar rate

25 | P a g e

ACCEPTED MANUSCRIPT P a g e | 26

AC C

EP

TE D

M AN U

SC

RI PT

x) Anterior rate

26 | P a g e

ACCEPTED MANUSCRIPT P a g e | 27

AC C

EP

TE D

M AN U

SC

RI PT

y) Posterior rate

27 | P a g e

ACCEPTED MANUSCRIPT P a g e | 28

AC C

EP

TE D

M AN U

SC

RI PT

2) Cumulative meta-analysis of studies reporting perioperative outcomes

28 | P a g e

ACCEPTED MANUSCRIPT P a g e | 29

AC C

EP

TE D

M AN U

SC

RI PT

a) Operative time, min

29 | P a g e

ACCEPTED MANUSCRIPT P a g e | 30

AC C

EP

TE D

M AN U

SC

RI PT

b) Estimated blood loss, ml

30 | P a g e

ACCEPTED MANUSCRIPT P a g e | 31

AC C

EP

TE D

M AN U

SC

RI PT

c) Warm Ischemia time, min

31 | P a g e

ACCEPTED MANUSCRIPT P a g e | 32

AC C

EP

TE D

M AN U

SC

RI PT

d) Conversion to radical nephrectomy rate

32 | P a g e

ACCEPTED MANUSCRIPT P a g e | 33

AC C

EP

TE D

M AN U

SC

RI PT

e) Conversion to open partial nephrectomy rate

33 | P a g e

ACCEPTED MANUSCRIPT P a g e | 34

EP

TE D

M AN U

SC

RI PT

Transfusions rate

AC C

f)

34 | P a g e

ACCEPTED MANUSCRIPT P a g e | 35

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall intraoperative complications rate

35 | P a g e

ACCEPTED MANUSCRIPT P a g e | 36

AC C

EP

TE D

M AN U

SC

RI PT

h) Overall postoperative complications rate

36 | P a g e

ACCEPTED MANUSCRIPT P a g e | 37

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo < 3 complication rate

AC C

i)

37 | P a g e

ACCEPTED MANUSCRIPT P a g e | 38

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo ≥ 3 complications rate

AC C

j)

38 | P a g e

ACCEPTED MANUSCRIPT P a g e | 39

AC C

EP

TE D

M AN U

SC

RI PT

k) Length of hospital stay, days

39 | P a g e

ACCEPTED MANUSCRIPT P a g e | 40

EP

TE D

M AN U

SC

RI PT

Readmission rate

AC C

l)

40 | P a g e

ACCEPTED MANUSCRIPT P a g e | 41

AC C

EP

TE D

M AN U

SC

RI PT

m) Latest postoperative % eGFR change

41 | P a g e

ACCEPTED MANUSCRIPT P a g e | 42

AC C

EP

TE D

M AN U

SC

RI PT

n) Positive margins rate

42 | P a g e

ACCEPTED MANUSCRIPT P a g e | 43

AC C

EP

TE D

M AN U

SC

RI PT

o) Overall mortality rate

43 | P a g e

ACCEPTED MANUSCRIPT P a g e | 44

AC C

EP

TE D

M AN U

SC

RI PT

p) Cancer specific mortality

44 | P a g e

ACCEPTED MANUSCRIPT P a g e | 45

AC C

EP

TE D

M AN U

SC

RI PT

q) Recurrence rate

45 | P a g e

ACCEPTED MANUSCRIPT P a g e | 46

AC C

EP

TE D

M AN U

SC

RI PT

3) Sensitivity meta-analysis of perioperative outcomes in studies reporting > 70 procedures

46 | P a g e

ACCEPTED MANUSCRIPT P a g e | 47

AC C

EP

TE D

M AN U

SC

RI PT

a) Operative time, min

47 | P a g e

ACCEPTED MANUSCRIPT P a g e | 48

AC C

EP

TE D

M AN U

SC

RI PT

b) Estimated blood loss, ml

48 | P a g e

ACCEPTED MANUSCRIPT P a g e | 49

AC C

EP

TE D

M AN U

SC

RI PT

c) Warm Ischemia time, min

49 | P a g e

ACCEPTED MANUSCRIPT P a g e | 50

AC C

EP

TE D

M AN U

SC

RI PT

d) Conversion to radical nephrectomy rate

50 | P a g e

ACCEPTED MANUSCRIPT P a g e | 51

AC C

EP

TE D

M AN U

SC

RI PT

e) Conversion to open partial nephrectomy rate

51 | P a g e

ACCEPTED MANUSCRIPT P a g e | 52

EP

TE D

M AN U

SC

RI PT

Transfusions rate

AC C

f)

52 | P a g e

ACCEPTED MANUSCRIPT P a g e | 53

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall intraoperative complications rate

53 | P a g e

ACCEPTED MANUSCRIPT P a g e | 54

AC C

EP

TE D

M AN U

SC

RI PT

h) Overall postoperative complications rate

54 | P a g e

ACCEPTED MANUSCRIPT P a g e | 55

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo < 3 complication rate

AC C

i)

55 | P a g e

ACCEPTED MANUSCRIPT P a g e | 56

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo ≥ 3 complications rate

AC C

j)

56 | P a g e

ACCEPTED MANUSCRIPT P a g e | 57

AC C

EP

TE D

M AN U

SC

RI PT

k) Length of hospital stay, days

57 | P a g e

ACCEPTED MANUSCRIPT P a g e | 58

EP

TE D

M AN U

SC

RI PT

Readmission rate

AC C

l)

58 | P a g e

ACCEPTED MANUSCRIPT P a g e | 59

AC C

EP

TE D

M AN U

SC

RI PT

m) Latest postoperative % eGFR change

59 | P a g e

ACCEPTED MANUSCRIPT P a g e | 60

AC C

EP

TE D

M AN U

SC

RI PT

n) Positive margins rate

60 | P a g e

ACCEPTED MANUSCRIPT P a g e | 61

AC C

EP

TE D

M AN U

SC

RI PT

o) Overall mortality rate

61 | P a g e

ACCEPTED MANUSCRIPT P a g e | 62

AC C

EP

TE D

M AN U

SC

RI PT

p) Cancer specific mortality

62 | P a g e

ACCEPTED MANUSCRIPT P a g e | 63

AC C

EP

TE D

M AN U

SC

RI PT

q) Recurrence rate

63 | P a g e

ACCEPTED MANUSCRIPT P a g e | 64

AC C

EP

TE D

M AN U

SC

RI PT

4) Sensitivity meta-analysis of studies reporting complex renal masses

64 | P a g e

ACCEPTED MANUSCRIPT P a g e | 65

AC C

EP

TE D

M AN U

SC

RI PT

a) Operative time, min

65 | P a g e

ACCEPTED MANUSCRIPT P a g e | 66

AC C

EP

TE D

M AN U

SC

RI PT

b) Estimated blood loss, ml

66 | P a g e

ACCEPTED MANUSCRIPT P a g e | 67

AC C

EP

TE D

M AN U

SC

RI PT

c) Warm Ischemia time, min

67 | P a g e

ACCEPTED MANUSCRIPT P a g e | 68

AC C

EP

TE D

M AN U

SC

RI PT

d) Conversion to radical nephrectomy rate

68 | P a g e

ACCEPTED MANUSCRIPT P a g e | 69

AC C

EP

TE D

M AN U

SC

RI PT

e) Transfusions rate

69 | P a g e

ACCEPTED MANUSCRIPT P a g e | 70 Overall intraoperative complications rate

AC C

EP

TE D

M AN U

SC

RI PT

f)

70 | P a g e

ACCEPTED MANUSCRIPT P a g e | 71

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall postoperative complications rate

71 | P a g e

ACCEPTED MANUSCRIPT P a g e | 72

AC C

EP

TE D

M AN U

SC

RI PT

h) Clavien-Dindo < 3 complication rate

72 | P a g e

ACCEPTED MANUSCRIPT P a g e | 73 Clavien-Dindo ≥ 3 complications rate

AC C

EP

TE D

M AN U

SC

RI PT

i)

73 | P a g e

ACCEPTED MANUSCRIPT P a g e | 74 Length of hospital stay, days

AC C

EP

TE D

M AN U

SC

RI PT

j)

74 | P a g e

ACCEPTED MANUSCRIPT P a g e | 75

AC C

EP

TE D

M AN U

SC

RI PT

k) Latest postoperative % eGFR change

75 | P a g e

ACCEPTED MANUSCRIPT P a g e | 76 Positive margins rate

AC C

EP

TE D

M AN U

SC

RI PT

l)

76 | P a g e

ACCEPTED MANUSCRIPT P a g e | 77

AC C

EP

TE D

M AN U

SC

RI PT

m) Overall mortality rate

77 | P a g e

ACCEPTED MANUSCRIPT P a g e | 78

AC C

EP

TE D

M AN U

SC

RI PT

n) Cancer specific mortality

78 | P a g e

ACCEPTED MANUSCRIPT P a g e | 79

AC C

EP

TE D

M AN U

SC

RI PT

o) Recurrence rate

79 | P a g e

ACCEPTED MANUSCRIPT P age |1

M AN U

SC

META-ANALYSES

RI PT

TRANSPERITONEAL VS RETROPERITONEAL PARTIAL NEPHRECTOMY

1) Cumulative meta-analysis of studies reporting baseline characteristics

AC C

EP

TE D

2) Cumulative meta-analysis of studies reporting perioperative outcomes

1|P age

ACCEPTED MANUSCRIPT P age |2

AC C

EP

TE D

M AN U

SC

RI PT

1) Cumulative meta-analysis of studies reporting baseline characteristics

2|P age

ACCEPTED MANUSCRIPT P age |3

AC C

EP

TE D

M AN U

SC

RI PT

a) Age

3|P age

ACCEPTED MANUSCRIPT P age |4

AC C

EP

TE D

M AN U

SC

RI PT

b) Gender male rate

4|P age

ACCEPTED MANUSCRIPT P age |5

AC C

EP

TE D

M AN U

SC

RI PT

c) Gender female rate

5|P age

ACCEPTED MANUSCRIPT P age |6

AC C

EP

TE D

M AN U

SC

RI PT

d) BMI

6|P age

ACCEPTED MANUSCRIPT P age |7

AC C

EP

TE D

M AN U

SC

RI PT

e) ASA

7|P age

ACCEPTED MANUSCRIPT P age |8

EP

TE D

M AN U

SC

RI PT

Preoperative eGFR

AC C

f)

8|P age

ACCEPTED MANUSCRIPT P age |9

AC C

EP

TE D

M AN U

SC

RI PT

g) Tumor size

9|P age

ACCEPTED MANUSCRIPT P a g e | 10

AC C

EP

TE D

M AN U

SC

RI PT

h) T1a rate

10 | P a g e

ACCEPTED MANUSCRIPT P a g e | 11

EP

TE D

M AN U

SC

RI PT

T1b rate

AC C

i)

11 | P a g e

ACCEPTED MANUSCRIPT P a g e | 12

EP

TE D

M AN U

SC

RI PT

Right side tumor rate

AC C

j)

12 | P a g e

ACCEPTED MANUSCRIPT P a g e | 13

AC C

EP

TE D

M AN U

SC

RI PT

k) Left side tumor rate

13 | P a g e

ACCEPTED MANUSCRIPT P a g e | 14

EP

TE D

M AN U

SC

RI PT

Mean R.E.N.A.L score

AC C

l)

14 | P a g e

ACCEPTED MANUSCRIPT P a g e | 15

AC C

EP

TE D

M AN U

SC

RI PT

m) Mean PADUA score

15 | P a g e

ACCEPTED MANUSCRIPT P a g e | 16

AC C

EP

TE D

M AN U

SC

RI PT

n) Anterior rate

16 | P a g e

ACCEPTED MANUSCRIPT P a g e | 17

AC C

EP

TE D

M AN U

SC

RI PT

o) Posterior rate

17 | P a g e

ACCEPTED MANUSCRIPT P a g e | 18

AC C

EP

TE D

M AN U

SC

RI PT

2) Cumulative meta-analysis of studies reporting perioperative outcomes

18 | P a g e

ACCEPTED MANUSCRIPT P a g e | 19

AC C

EP

TE D

M AN U

SC

RI PT

a) Operative time, min

19 | P a g e

ACCEPTED MANUSCRIPT P a g e | 20

AC C

EP

TE D

M AN U

SC

RI PT

b) Estimated blood loss, ml

20 | P a g e

ACCEPTED MANUSCRIPT P a g e | 21

AC C

EP

TE D

M AN U

SC

RI PT

c) Warm Ischemia time, min

21 | P a g e

ACCEPTED MANUSCRIPT P a g e | 22

AC C

EP

TE D

M AN U

SC

RI PT

d) Conversion to radical nephrectomy rate

22 | P a g e

ACCEPTED MANUSCRIPT P a g e | 23

AC C

EP

TE D

M AN U

SC

RI PT

e) Conversion to open partial nephrectomy rate

23 | P a g e

ACCEPTED MANUSCRIPT P a g e | 24

EP

TE D

M AN U

SC

RI PT

Transfusions rate

AC C

f)

24 | P a g e

ACCEPTED MANUSCRIPT P a g e | 25

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall intraoperative complications rate

25 | P a g e

ACCEPTED MANUSCRIPT P a g e | 26

AC C

EP

TE D

M AN U

SC

RI PT

h) Overall postoperative complications rate

26 | P a g e

ACCEPTED MANUSCRIPT P a g e | 27

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo < 3 complication rate

AC C

i)

27 | P a g e

ACCEPTED MANUSCRIPT P a g e | 28

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo ≥ 3 complications rate

AC C

j)

28 | P a g e

ACCEPTED MANUSCRIPT P a g e | 29

AC C

EP

TE D

M AN U

SC

RI PT

k) Length of hospital stay, days

29 | P a g e

ACCEPTED MANUSCRIPT P a g e | 30

EP

TE D

M AN U

SC

RI PT

Readmission rate

AC C

l)

30 | P a g e

ACCEPTED MANUSCRIPT P a g e | 31

AC C

EP

TE D

M AN U

SC

RI PT

m) Latest postoperative % eGFR change

31 | P a g e

ACCEPTED MANUSCRIPT P a g e | 32

AC C

EP

TE D

M AN U

SC

RI PT

n) Positive margins rate

32 | P a g e

ACCEPTED MANUSCRIPT P a g e | 33

AC C

EP

TE D

M AN U

SC

RI PT

o) Overall mortality rate

33 | P a g e

ACCEPTED MANUSCRIPT P a g e | 34

AC C

EP

TE D

M AN U

SC

RI PT

p) Cancer specific mortality

34 | P a g e

ACCEPTED MANUSCRIPT P a g e | 35

AC C

EP

TE D

M AN U

SC

RI PT

q) Recurrence rate

35 | P a g e

ACCEPTED MANUSCRIPT P age |1

OFF CLAMP VS ON CLAMP

M AN U

SC

META-ANALYSES

RI PT

PARTIAL NEPHRECTOMY

1) Cumulative meta-analysis of studies reporting baseline characteristics

AC C

EP

TE D

2) Cumulative meta-analysis of studies reporting perioperative outcomes

1|P age

ACCEPTED MANUSCRIPT P age |2

AC C

EP

TE D

M AN U

SC

RI PT

1) Cumulative meta-analysis of studies reporting baseline characteristics

2|P age

ACCEPTED MANUSCRIPT P age |3

AC C

EP

TE D

M AN U

SC

RI PT

a) Age

3|P age

ACCEPTED MANUSCRIPT P age |4

AC C

EP

TE D

M AN U

SC

RI PT

b) Gender male rate

4|P age

ACCEPTED MANUSCRIPT P age |5

AC C

EP

TE D

M AN U

SC

RI PT

c) Gender female rate

5|P age

ACCEPTED MANUSCRIPT P age |6

AC C

EP

TE D

M AN U

SC

RI PT

d) BMI

6|P age

ACCEPTED MANUSCRIPT P age |7

AC C

EP

TE D

M AN U

SC

RI PT

e) ASA

7|P age

ACCEPTED MANUSCRIPT P age |8

EP

TE D

M AN U

SC

RI PT

Preoperative eGFR

AC C

f)

8|P age

ACCEPTED MANUSCRIPT P age |9

AC C

EP

TE D

M AN U

SC

RI PT

g) Tumor size

9|P age

ACCEPTED MANUSCRIPT P a g e | 10

AC C

EP

TE D

M AN U

SC

RI PT

h) T1a rate

10 | P a g e

ACCEPTED MANUSCRIPT P a g e | 11

EP

TE D

M AN U

SC

RI PT

T1b rate

AC C

i)

11 | P a g e

ACCEPTED MANUSCRIPT P a g e | 12

EP

TE D

M AN U

SC

RI PT

T2 rate

AC C

j)

12 | P a g e

ACCEPTED MANUSCRIPT P a g e | 13

AC C

EP

TE D

M AN U

SC

RI PT

k) T3a rate

13 | P a g e

ACCEPTED MANUSCRIPT P a g e | 14

EP

TE D

M AN U

SC

RI PT

T4 rate

AC C

l)

14 | P a g e

ACCEPTED MANUSCRIPT P a g e | 15

AC C

EP

TE D

M AN U

SC

RI PT

m) Right side tumor rate

15 | P a g e

ACCEPTED MANUSCRIPT P a g e | 16

AC C

EP

TE D

M AN U

SC

RI PT

n) Left side tumor rate

16 | P a g e

ACCEPTED MANUSCRIPT P a g e | 17

AC C

EP

TE D

M AN U

SC

RI PT

o) Mean R.E.N.A.L score

17 | P a g e

ACCEPTED MANUSCRIPT P a g e | 18

AC C

EP

TE D

M AN U

SC

RI PT

p) Mean PADUA score

18 | P a g e

ACCEPTED MANUSCRIPT P a g e | 19

AC C

EP

TE D

M AN U

SC

RI PT

q) Endophytic rate

19 | P a g e

ACCEPTED MANUSCRIPT P a g e | 20

AC C

EP

TE D

M AN U

SC

RI PT

r) Exophytic rate

20 | P a g e

ACCEPTED MANUSCRIPT P a g e | 21

AC C

EP

TE D

M AN U

SC

RI PT

s) Transperitoneal approach

21 | P a g e

ACCEPTED MANUSCRIPT P a g e | 22

AC C

EP

TE D

M AN U

SC

RI PT

t) Retroperitoneal approach

22 | P a g e

ACCEPTED MANUSCRIPT P a g e | 23

AC C

EP

TE D

M AN U

SC

RI PT

2) Cumulative meta-analysis of studies reporting perioperative outcomes

23 | P a g e

ACCEPTED MANUSCRIPT P a g e | 24

AC C

EP

TE D

M AN U

SC

RI PT

a) Operative time, min

24 | P a g e

ACCEPTED MANUSCRIPT P a g e | 25

AC C

EP

TE D

M AN U

SC

RI PT

b) Estimated blood loss, ml

25 | P a g e

ACCEPTED MANUSCRIPT P a g e | 26

AC C

EP

TE D

M AN U

SC

RI PT

c) Conversion to radical nephrectomy rate

26 | P a g e

ACCEPTED MANUSCRIPT P a g e | 27

AC C

EP

TE D

M AN U

SC

RI PT

d) Conversion to open partial nephrectomy rate

27 | P a g e

ACCEPTED MANUSCRIPT P a g e | 28

AC C

EP

TE D

M AN U

SC

RI PT

e) Transfusions rate

28 | P a g e

ACCEPTED MANUSCRIPT P a g e | 29

EP

TE D

M AN U

SC

RI PT

Overall intraoperative complications rate

AC C

f)

29 | P a g e

ACCEPTED MANUSCRIPT P a g e | 30

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall postoperative complications rate

30 | P a g e

ACCEPTED MANUSCRIPT P a g e | 31

AC C

EP

TE D

M AN U

SC

RI PT

h) Clavien-Dindo < 3 complication rate

31 | P a g e

ACCEPTED MANUSCRIPT P a g e | 32

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo ≥ 3 complications rate

AC C

i)

32 | P a g e

ACCEPTED MANUSCRIPT P a g e | 33

EP

TE D

M AN U

SC

RI PT

Length of hospital stay, days

AC C

j)

33 | P a g e

ACCEPTED MANUSCRIPT P a g e | 34

AC C

EP

TE D

M AN U

SC

RI PT

k) Latest postoperative % eGFR change

34 | P a g e

ACCEPTED MANUSCRIPT P a g e | 35

EP

TE D

M AN U

SC

RI PT

Positive margins rate

AC C

l)

35 | P a g e

ACCEPTED MANUSCRIPT P a g e | 36

AC C

EP

TE D

M AN U

SC

RI PT

m) Recurrence rate

36 | P a g e

ACCEPTED MANUSCRIPT P age |1

SELECTIVE/SUPERSELECTIVE VS ON CLAMP

M AN U

SC

META-ANALYSES

RI PT

PARTIAL NEPHRECTOMY

1) Cumulative meta-analysis of studies reporting baseline characteristics

AC C

EP

TE D

2) Cumulative meta-analysis of studies reporting perioperative outcomes

1|P age

ACCEPTED MANUSCRIPT P age |2

AC C

EP

TE D

M AN U

SC

RI PT

1) Cumulative meta-analysis of studies reporting baseline characteristics

2|P age

ACCEPTED MANUSCRIPT P age |3

AC C

EP

TE D

M AN U

SC

RI PT

a) Age

3|P age

ACCEPTED MANUSCRIPT P age |4

AC C

EP

TE D

M AN U

SC

RI PT

b) Gender male rate

4|P age

ACCEPTED MANUSCRIPT P age |5

AC C

EP

TE D

M AN U

SC

RI PT

c) Gender female rate

5|P age

ACCEPTED MANUSCRIPT P age |6

AC C

EP

TE D

M AN U

SC

RI PT

d) BMI

6|P age

ACCEPTED MANUSCRIPT P age |7

AC C

EP

TE D

M AN U

SC

RI PT

e) ASA

7|P age

ACCEPTED MANUSCRIPT P age |8

EP

TE D

M AN U

SC

RI PT

Preoperative eGFR

AC C

f)

8|P age

ACCEPTED MANUSCRIPT P age |9

AC C

EP

TE D

M AN U

SC

RI PT

g) Tumor size

9|P age

ACCEPTED MANUSCRIPT P a g e | 10

AC C

EP

TE D

M AN U

SC

RI PT

h) T1a rate

10 | P a g e

ACCEPTED MANUSCRIPT P a g e | 11

EP

TE D

M AN U

SC

RI PT

T1b rate

AC C

i)

11 | P a g e

ACCEPTED MANUSCRIPT P a g e | 12

EP

TE D

M AN U

SC

RI PT

T2 rate

AC C

j)

12 | P a g e

ACCEPTED MANUSCRIPT P a g e | 13

AC C

EP

TE D

M AN U

SC

RI PT

k) T3a rate

13 | P a g e

ACCEPTED MANUSCRIPT P a g e | 14

EP

TE D

M AN U

SC

RI PT

Right side tumor rate

AC C

l)

14 | P a g e

ACCEPTED MANUSCRIPT P a g e | 15

AC C

EP

TE D

M AN U

SC

RI PT

m) Left side tumor rate

15 | P a g e

ACCEPTED MANUSCRIPT P a g e | 16

AC C

EP

TE D

M AN U

SC

RI PT

n) Mean R.E.N.A.L score

16 | P a g e

ACCEPTED MANUSCRIPT P a g e | 17

AC C

EP

TE D

M AN U

SC

RI PT

o) Mean PADUA score

17 | P a g e

ACCEPTED MANUSCRIPT P a g e | 18

AC C

EP

TE D

M AN U

SC

RI PT

p) Endophytic rate

18 | P a g e

ACCEPTED MANUSCRIPT P a g e | 19

AC C

EP

TE D

M AN U

SC

RI PT

q) Exophytic rate

19 | P a g e

ACCEPTED MANUSCRIPT P a g e | 20

AC C

EP

TE D

M AN U

SC

RI PT

2) Cumulative meta-analysis of studies reporting perioperative outcomes

20 | P a g e

ACCEPTED MANUSCRIPT P a g e | 21

AC C

EP

TE D

M AN U

SC

RI PT

a) Operative time, min

21 | P a g e

ACCEPTED MANUSCRIPT P a g e | 22

AC C

EP

TE D

M AN U

SC

RI PT

b) Estimated blood loss, ml

22 | P a g e

ACCEPTED MANUSCRIPT P a g e | 23

AC C

EP

TE D

M AN U

SC

RI PT

c) Conversion to open partial nephrectomy rate

23 | P a g e

ACCEPTED MANUSCRIPT P a g e | 24

AC C

EP

TE D

M AN U

SC

RI PT

d) Conversion to open partial nephrectomy

24 | P a g e

ACCEPTED MANUSCRIPT P a g e | 25

AC C

EP

TE D

M AN U

SC

RI PT

e) Transfusions rate

25 | P a g e

ACCEPTED MANUSCRIPT P a g e | 26

EP

TE D

M AN U

SC

RI PT

Overall intraoperative complications rate

AC C

f)

26 | P a g e

ACCEPTED MANUSCRIPT P a g e | 27

AC C

EP

TE D

M AN U

SC

RI PT

g) Overall postoperative complications rate

27 | P a g e

ACCEPTED MANUSCRIPT P a g e | 28

AC C

EP

TE D

M AN U

SC

RI PT

h) Clavien-Dindo < 3 complication rate

28 | P a g e

ACCEPTED MANUSCRIPT P a g e | 29

EP

TE D

M AN U

SC

RI PT

Clavien-Dindo ≥ 3 complications rate

AC C

i)

29 | P a g e

ACCEPTED MANUSCRIPT P a g e | 30

EP

TE D

M AN U

SC

RI PT

Length of hospital stay, days

AC C

j)

30 | P a g e

ACCEPTED MANUSCRIPT P a g e | 31

AC C

EP

TE D

M AN U

SC

RI PT

k) Latest postoperative % eGFR change

31 | P a g e

ACCEPTED MANUSCRIPT P a g e | 32

EP

TE D

M AN U

SC

RI PT

Positive margins rate

AC C

l)

32 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

P a g e | 33

33 | P a g e

ACCEPTED MANUSCRIPT P age |1

EARLY UNCLAMP VS ON CLAMP

M AN U

SC

META-ANALYSES

RI PT

PARTIAL NEPHRECTOMY

1) Cumulative meta-analysis of studies reporting baseline characteristics

AC C

EP

TE D

2) Cumulative meta-analysis of studies reporting perioperative outcomes

1|P age

ACCEPTED MANUSCRIPT P age |2

AC C

EP

TE D

M AN U

SC

RI PT

1) Cumulative meta-analysis of studies reporting baseline characteristics

2|P age

ACCEPTED MANUSCRIPT P age |3

AC C

EP

TE D

M AN U

SC

RI PT

a) Age

3|P age

ACCEPTED MANUSCRIPT P age |4

AC C

EP

TE D

M AN U

SC

RI PT

b) Gender male rate

4|P age

ACCEPTED MANUSCRIPT P age |5

AC C

EP

TE D

M AN U

SC

RI PT

c) Gender female rate

5|P age

ACCEPTED MANUSCRIPT P age |6

AC C

EP

TE D

M AN U

SC

RI PT

d) BMI

6|P age

ACCEPTED MANUSCRIPT P age |7

AC C

EP

TE D

M AN U

SC

RI PT

e) ASA

7|P age

ACCEPTED MANUSCRIPT P age |8

EP

TE D

M AN U

SC

RI PT

Preoperative eGFR

AC C

f)

8|P age

ACCEPTED MANUSCRIPT P age |9

AC C

EP

TE D

M AN U

SC

RI PT

g) Tumor size

9|P age

ACCEPTED MANUSCRIPT P a g e | 10

AC C

EP

TE D

M AN U

SC

RI PT

h) T1a rate

10 | P a g e

ACCEPTED MANUSCRIPT P a g e | 11

EP

TE D

M AN U

SC

RI PT

T1b rate

AC C

i)

11 | P a g e

ACCEPTED MANUSCRIPT P a g e | 12

EP

TE D

M AN U

SC

RI PT

T2 rate

AC C

j)

12 | P a g e

ACCEPTED MANUSCRIPT P a g e | 13

AC C

EP

TE D

M AN U

SC

RI PT

k) T3a rate

13 | P a g e

ACCEPTED MANUSCRIPT P a g e | 14

EP

TE D

M AN U

SC

RI PT

Right side tumor rate

AC C

l)

14 | P a g e

ACCEPTED MANUSCRIPT P a g e | 15

AC C

EP

TE D

M AN U

SC

RI PT

m) Left side tumor rate

15 | P a g e

ACCEPTED MANUSCRIPT P a g e | 16

AC C

EP

TE D

M AN U

SC

RI PT

n) Mean R.E.N.A.L score

16 | P a g e

ACCEPTED MANUSCRIPT P a g e | 17

AC C

EP

TE D

M AN U

SC

RI PT

o) Mean PADUA score

17 | P a g e

ACCEPTED MANUSCRIPT P a g e | 18

AC C

EP

TE D

M AN U

SC

RI PT

p) Endophytic rate

18 | P a g e

ACCEPTED MANUSCRIPT P a g e | 19

AC C

EP

TE D

M AN U

SC

RI PT

q) Exophytic rate

19 | P a g e

ACCEPTED MANUSCRIPT P a g e | 20

AC C

EP

TE D

M AN U

SC

RI PT

2) Cumulative meta-analysis of studies reporting perioperative outcomes

20 | P a g e

ACCEPTED MANUSCRIPT P a g e | 21

AC C

EP

TE D

M AN U

SC

RI PT

a) Operative time, min

21 | P a g e

ACCEPTED MANUSCRIPT P a g e | 22

AC C

EP

TE D

M AN U

SC

RI PT

b) Estimated blood loss, ml

22 | P a g e

ACCEPTED MANUSCRIPT P a g e | 23

AC C

EP

TE D

M AN U

SC

RI PT

c) Warm ischemia time

23 | P a g e

ACCEPTED MANUSCRIPT P a g e | 24

AC C

EP

TE D

M AN U

SC

RI PT

d) Transfusions rate

24 | P a g e

ACCEPTED MANUSCRIPT P a g e | 25

AC C

EP

TE D

M AN U

SC

RI PT

e) Overall intraoperative complications rate

25 | P a g e

ACCEPTED MANUSCRIPT P a g e | 26

EP

TE D

M AN U

SC

RI PT

Overall postoperative complications rate

AC C

f)

26 | P a g e

ACCEPTED MANUSCRIPT P a g e | 27

AC C

EP

TE D

M AN U

SC

RI PT

g) Clavien-Dindo < 3 complication rate

27 | P a g e

ACCEPTED MANUSCRIPT P a g e | 28

AC C

EP

TE D

M AN U

SC

RI PT

h) Clavien-Dindo ≥ 3 complications rate

28 | P a g e

ACCEPTED MANUSCRIPT P a g e | 29

EP

TE D

M AN U

SC

RI PT

Length of hospital stay, days

AC C

i)

29 | P a g e

ACCEPTED MANUSCRIPT P a g e | 30

EP

TE D

M AN U

SC

RI PT

Latest postoperative % eGFR change

AC C

j)

30 | P a g e

ACCEPTED MANUSCRIPT P a g e | 31

AC C

EP

TE D

M AN U

SC

RI PT

k) Positive margins rate

31 | P a g e

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

P a g e | 32

32 | P a g e

OPN vs RPN risk of bias: NOS

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

LPN vs RPN risk of bias: NOS

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

Transperitoneal vs Retroperitoneal risk of bias: NOS

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

Hilar control risk of bias: NOS

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT