Comparison Robotic versus laparoscopic partial nephrectomy for Complex Renal Tumors (with a RENAL nephrometry score ≥ 7): a meta-analysis

To compare the perioperative outcomes of Robotic partial nephrectomy (RPN) versus laparoscopic partial nephrectomy (LPN). We searched PubMed, EMBASE and the Cochrane Central Register for studies from 2000 to 2020 to evaluate the perioperative outcomes RPN and LPN in patients with a RENALnephrometry score ≥ 7. We used RevMan 5.2 to pool the data. Seven studies were acquired in our study. No signicant differences were found in the estimated blood loss (WMD: WMD: 34.49, 95% CI -75.16-144.14, p=0.54), hospital stay (WMD: -0.59 95% CI -1.24–0.06, p=0.07), operating time (WMD: -22.45, 95%CI: -35.06 to-9.85, ), postive surgical margin (OR: 0.85, 95% CI 0.65–1.11, p =0.23) and transfusion (OR: 0.72, 95% CI 0.48–1.08, p =0.11).between the two groups. RPN get better outcomes in postoperative renal function (WMD: 3.32, 95% CI 0.73–5.91, p=0.01), warm ischenia time (WMD: -6.96, 95% CI -7.30–-6.62, p <0.0001), conversion( OR: 0.34, 95%CI: 0.17 to 0.66, p=0.002) and intraoperative complication (OR: 0.52, 95% CI 0.28–0.97, p=0.04). a meta-analysis showed that RPN can achieve comparable outcomes in estimated blood loss, hospital stay, operating time, postive surgical margin and transfusion. RPN achieve better outcomes in postoperative renal function, warm ischenia time, conversion and intraoperative complication. More RCTs should be performed to clarify the effectiveness of RPN and LPN.


Abstract Background
To compare the perioperative outcomes of Robotic partial nephrectomy (RPN) versus laparoscopic partial nephrectomy (LPN).

Methods
We searched PubMed, EMBASE and the Cochrane Central Register for studies from 2000 to 2020 to evaluate the perioperative outcomes RPN and LPN in patients with a RENALnephrometry score≥7. We used RevMan 5.2 to pool the data.
Conclusion RPN could get better perioerative clinical outcomes than LPN for treatment of Complex Renal Tumors( with a RENALnephrometry score≥7).

Background
Partial nephrectomy (PN) or Nephron-sparing Surgery (NSS) has widely be regarded as the gold standard of surgical stragety for clinical T1 renal tumors [1].
NSS can acquire equivalent oncologic outcomes and better postoperative renal function compared to those of radical nephrectomy. In 1993, Gill et al. rstly introduced laparoscopic partial nephrectomy (LPN) in patients with a single renal tumor [2]. LPN has the advantage of reaching similar oncological outcomes, shorter length of hospital stay and lower estimated blood loss. So, LPN has been widely used for small renal tumors during the past decades [2][3][4]. Despite the population of LPN techniques, there were also several limitations, including technical demanding intracorporeal sutured reconstruction skills and di culty of tumour excision [5].
Robot-assisted partial nephrectomy was rstly reported in 2004, it has become a popular surgical method to clinical T1 renal tumors. The main advantages of the da Vinci® Surgical system consisting of the three-dimensional high-de nition vision of the surgical eld, a great range of wristed instruments, higher precision in the surgical dissection and easier for intracorporeal sutured reconstruction made RPN more popular than LPN [5][6][7].
Several meta-analyses had reported two surgical methods for renal tumors[8-10]. Aboumarzouk et al. performed a meta-analysis including 717 patients comparing robotic partial nephrectomy (RPN) with laparoscopic partial nephrectomy (LPN). They found that RPN could be a safe and feasible option as regard to LPN[8]. Choi et al. conducted a meta-analysis included 23 studies involving 2240 patients found that RPN acquire better recovery of postoperative renal function and lower rate of conversion rate to radical nephrectomy [10]. However, no meta-analysis has performed for comparing the RPN and LPN for treatment of complex renal tumors with RENAL nephrometry score ≥ 7. The aim of this meta-analysis was to perioperative, postoperative renal functional outcomes And oncological outcomes between RPN and LPN for complex renal tumors with RENAL nephrometry score ≥ 7.

Search strategy
We conducted this meta-analysis following the Preferred Reporting Items for Systematic Reviews and MetaAnalysis (PRISMA) guidelines. We relevant studies in PubMed, EMBASE and the Cochrane Central Register published in English between 2000 and 2020. We used the following search terms: "robotic partial nephrectomy (RPN) [MeSH]", "laparoscopic partial nephrectomy (LPN) [MeSH]", "renal tumor* [MeSH]", and"RENAL nephrometry score ≥7* OR complex renal tumors *". We also used the combined Boolean operators "AND" or "OR" in the title/abstract.

Inclusion and exclusion criteria
The inclusion criteria were as follows: (1) comparative study of RPN and LPN for the treatment of renal tumors with RENAL nephrometry score ≥7; (2) studies that contained at least one of the following outcomes: estimated blood loss, length of hospital stay, intraoperative complications, postoperative complications, operative time, conversion rate, positive surgical margin (PSM), transfusion, warm ischemia time, postoperative renal function; (3) follow-up duration longer than 6 months; (4). The exclusion criteria were as follows: (1) case reports, reviews, editorial comments, meeting abstracts and articles without applicable data; (2) studies with insu cient data, such as missing the SD (standard deviation) and could not acquire data;(3) studies that were not comparative and renal tumors with the RENAL score<7. The process of identifying relevant studies is summarized in Fig. 1. Two investigators (YLJ and XX) reviewed the articles.

Data extraction
The two authors extracted data, such as the estimated blood loss, operating time, postive surgical margin, postoperative complications, intraoperative complications, hospital stay, confusion, conversion, postoperative renal function and warm ischemia time. Two reviewers (YLJ and XX) assessed the quality of the included studies.

Statistical analysis
We used Review Manager Version 5.2 software with the Mantel-Haenszel method (The Cochrane Collaboration, Oxford, UK) to conduct the analysis of the data. We used Cochran's Q to evaluate the heterogeneity; Q<50% or P>0.01 was showed of little heterogeneity. However, Q>50% or P<0.01 was associated with heterogeneity. For quantitative data, we used the standard mean difference (SMD) and 95% con dence interval (CI) or weight mean difference (WMD) and 95%CI to pool continuous data. We used the odds ratio (OR) and 95%CI to calculate binary data. The statistical signi cance level was 0.05.

Quality assessment of the included studies
We used the New-Ottawa Scale (NOS) to evaluate the included studies. The NOS scores were evaluated using a 9-point system. An NOS score of 7 or above is considered as higher quality, and an NOS score of 3 or below was believed to have a lower quality. For RCT, we assessed the risk of bias according to the Cochrane Collabortation handbook, version 5.0. Table 2 shows quality assessment of the included studies.

Warm ischemia time
The data of warm ischemia time were in four studies. There was a statistically signi cant difference in warm ischemia time between the RPN and LPN groups (n =824, 419 patients were in the RPN group, and 405 patients were in the LPN group, WMD: -6.96, 95% CI -7.30--6.62, p <0.0001, I 2 =0, randomeffects model, Fig.4).

Transfusion
Seven studies reported the transfusion in our meta-analysis. There no statistically signi cant difference in transfusion between the RPN and LPN groups (n =1307, 635 patients were in the RPN group, 672 patients were in the LPN group, OR: 0.72, 95% CI 0.48-1.08, p =0.11, I 2 =0, xed-effective model, Fig.5).

Hospital stay
We included four studies in this study. No statistically signi cant difference in the hospital stay between the RPN and LPN groups (n =824, 419 patients were in the RPN group, and 405 patients were in the LPN group, WMD: -0.59 95% CI -1.24-0.06, p=0.07, I 2 =86%, random-effects model, Fig.7).

Intraoperative complications
Five studies reported the intraoperative complications. There was a statistical signi cant difference in the intraoperative complications between the RPN and LPN groups (n =1040, 527 patients were in the RPN group, and 513 patients were in the LPN group, OR: 0.52, 95% CI 0.28-0.97, p=0.04, I 2 =0, xed effects model, Fig.8).

Postoperative complications
Data on postoperative complications were existing in seven studies. There was no statistically signi cant difference in postoperative complications between the RPN and LPN groups (n =1256, 635 patients were in the RPN group, 621 patients were in the LPN group, OR: 0.85, 95% CI 0.65-1.11, p=0.23, I 2 =0, xedeffective model, Fig.9).

Postoperative renal function
Three studies included in our meta-analysis to pool the postoperative renal function. There was a statistically signi cant difference in the postoperative function between the RPN and LPN groups (n =524, 235 patients were in the RPN group, and 289 patients were in the LPN group, WMD: 3.32, 95% CI 0.73-5.91, p=0.01, I 2 =57, random-effects model, Fig.10).

Postive surgical margin
Six studies reported the postive surgical margin. There was no statistically signi cant difference in the postive surgical margin between the RPN and LPN groups (n =1132, 573 patients were in the RPN group, and 559 patients were in the LPN group, OR: 0.69, 95% CI 0.27-1.78, p=0.45, I 2 =0, xed effects model, Fig.11).

Discussion
This meta-analysis is the rst study to compare the perioperative outcomes and postoperative recovery renal function. We found that no signi cant difference was found in the estimated blood loss, hospital stay, postoperative complication rates, positive surgical margin and transfusion between the RPN and LPN groups. The postoperative renal function, radical to conversion and warm ischemia time were lower in the RPN group than in the LPN group. In our meta-analysis, the pooled data of warm ischemia time indicated that the warm ischemia time in RPN group was shorter than LPN group. Choi et al. reported a similar outcome to us (p = 0.005) [10].
As regard to radical to conversion, our meta-analysis found that the RPN group had lower conversion rate than the LPN. However, Aboumarzouk et al conducted a meta-analysis included 717 patients found that the conversion rate had no signi cant difference between the RPN and LPN group (p = 0.84). This may be due to different baseline characteristics in different studies.
In our meta-analysis, the patients in RPN group got a better recovery in postoperative renal function than in LPN group. The RPN group showed a low warm ischemia time and a satisfactory postoperative eGFR rate. The postoperative renal function was thought to associated with the duration of warm ischemia time. When the warm ischemia time > 30 min, the postoperative had a evident decrease[16].
In our study, the warm ischemia time was lower in RPN group than LPN group. This could reach a quick renal function recovery. Instead, deng et al performed a study by propensity score-based analysis included 116 patients indicated that the eGFR decrease in baseline was similar between the two groups [11]. It could be deduced that RPN is favorable versus LPN in preserving renal function due to decreased WIT. This may be attributed to using precie handling instruments, three-dimensional magni ed vision and precise dissection of the renal pedicle and tumor resection are better conducted with robotic assistance. Kopp et al performed a study to analyze the related factors associated to postoperative renal function after partial nephrectomy. They found that RENAL score could predict estimated glomerular ltration rate and warm ischemia time [17]. In our meta-analysis, the pooled data of warm ischemia time had a high heterogeneity. This may relate to the tumor locations and surgeons had different surgical skills. Recently, Bertolo et al reported a study indicating that different reconstrunction methods could short the ischaemia and operating times [18]. The different suture skills may be the causes of high heterogeneity.
In our meta-analysis, we found that the operative time was shorter in RPN than in LPN group. Choi et al performed a meta-analysis compared the RPN and LPN for treatment of renal tumors [10]. They found that no signi cant difference between the two groups. This was not consistent with our study.
We found that the intraoperative complications were lower in RPN group compared to LPN group. However, zhang et al found no signi cant difference between the two groups (p = 0.78) [14]. Zhang et al performed a meta-analysis found that the intraoperative complications were had no signicant difference in the two groups [14]. In our study, we involved the patients with a RENAL nephrometry score ≥ 7 which may the resson of difference from Zhang's study.
Besides, the different surgeons have different surgical skill level to RPN or LPN.
This may lead to the difference between the two meta-analyses. Our meta-analysis also found that the positive surgical margin had no signi cant difference between RPN and LPN (p = 0.45). Similarly, zhang et al performed a meta-analysis nding that no signi cant difference was existent between RPN and LPN group (p = 0.61). Aboumarzouk et al also reported a similar outcome (p = 0.93).
In our meta-analysis, we found that the estimated blood loss had no signi cant difference bo etween RPN and LPN group. Zhang et al also found thant the estimated blood loss had no signi cant difference between the two groups (p = 0.75). This is consistent with our study. However, the high heterogeneity in estimated blood loss probably due to the difference in surgeons familiar to surgical process. However, chang et al also performed a propensity-scorematching study nding that RPN resulted in signi cantly lower mean estimated blood loss compared with LPN (P = 0.025) [19]. Several systematic review and meta-analyses reported a similar outcomes[8, 10, 20].
Our study also had several limitations. First, we did not include RCTs. This can lower the evidence of our study. Second, the included studies ahd different RENA scores and this could increase the heterogeneity. Besides, this also could lower the con dence of our meta-analysis. Additionally, the different studies had a range of variable tumor size. We did not balance this data. This could impact on warm ischemia time and postoperative renal function. We did not adjust the common baseline characteristics of patients. The different defenition of nomenclature and functional outcomes could lead to heterogeneity [21].
Third, conducted the oncological outcomes for the sake of data of of overall survival, recurrence free survival and cancer speic c survival. In our metaanalysis, some studies make a propensity score-based analysis and other did not. This could increase heteroneity. Alimi et al conducted a multicenter study involving different surgeons which also increase the heterogeneity. For the high heterogeneity, we did not conduct a sensitive analysis or subgroup analysis. We did not nd the causes of high heterogeneity. We compared the perioperative outcomes and postioerative renal function outcome.

Conclusions
Our meta-analysis showed that RPN can achieve comparable outcomes in estimated blood loss, hospital stay, operating time, postive surgical margin and transfusion. RPN achieve better outcomes in postoperative renal function, warm ischenia time, conversion and intraoperative complication. More RCTs should be performed to clarify the effectiveness of RPN and LPN.
Abbreviations RPN: Robotic partial nephrectomy: LPN: laparoscopic partial nephrectomy ESBL: estimated blood loss; CI: con dence interval; WMD: weight mean difference; OR: odds ratio; Declarations Ethics approval and consent to participate Not applicable.

Consent for publication
Not applicable.

Availability of data and materials
All data generated or analyzed during this study are included in this published article.

Competing interests
The authors declare that they have no competing interests.

Funding
Not applicable.

Authors Contributions
YLJ and LP designed the study. YLJ wrote the manuscript. YLJ, XX and PFS analyzed the data. HXH, STL and ZJB searched the articles. All authors read and approved the nal manuscript.    Page 8/9 Forest plot for operating time between the RPN and LPN.

Figure 3
Forest plot for estimated blood loss between the RPN and LPN.

Figure 4
Forest plot for warm ischemia time between the RPN and LPN.

Figure 5
Forest plot for transfusion between the RPN and LPN.

Figure 6
Forest plot for conversion between the RPN and LPN.

Figure 7
Page 9/9 Forest plot for hospital stay between the RPN and LPN.

Figure 8
Forest plot for intraoperative complications between the RPN and LPN.

Figure 9
Forest plot for postoperative complications between the RPN and LPN.

Figure 10
Forest plot for postoperative renal function between the RPN and LPN.

Figure 11
Forest plot for postive surgical margin between the RPN and LPN.