Skip to main content
PMC home page
PLOS ONE logoLink to PLOS ONE
. 2024 May 29;19(5):e0304031. doi: 10.1371/journal.pone.0304031

Robotic versus laparoscopic total mesorectal excision with lateral lymph node dissection for advanced rectal cancer: A systematic review and meta-analysis

Mohamed Ali Chaouch 1,‡,*, Mohammad Iqbal Hussain 2,‡, Adriano Carneiro da Costa 3, Alessandro Mazzotta 4, Bassem Krimi 5, Amine Gouader 5, Eddy Cotte 6, Jim Khan 2, Hani Oweira 7
Editor: Tsutomu Kumamoto8
PMCID: PMC11135705  PMID: 38809911

Abstract

Introduction

Lateral pelvic node dissection (LPND) poses significant technical challenges. Despite the advent of robotic surgery, determining the optimal minimally invasive approach remains a topic of debate. This study aimed to compare postoperative outcomes between robotic total mesorectal excision with LPND (R-LPND) and laparoscopic total mesorectal excision with LPND (L-LPND).

Methods

This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) 2020 and AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews) guidelines. Utilizing the RevMan 5.3.5 statistical package from the Cochrane Collaboration, a random-effects model was employed.

Results

Six eligible studies involving 652 patients (316 and 336 in the R-LPND and L-LPND groups, respectively) were retrieved. The robotic approach demonstrated favourable outcomes compared with the laparoscopic approach, manifesting in lower morbidity rates, reduced urinary complications, shorter hospital stays, and a higher number of harvested lateral pelvic lymph nodes. However, longer operative time was associated with the robotic approach. No significant differences were observed between the two groups regarding major complications, anastomotic leak, intra-abdominal infection, neurological complications, LPND time, overall recurrence, and local recurrence.

Conclusions

In summary, the robotic approach is a safe and feasible alternative for Total Mesorectal Excision (TME) with LPND in advanced rectal cancer. Notably, it is associated with lower morbidity, particularly a reduction in urinary complications, a shorter hospital stay and increased number of harvested lateral pelvic nodes. The trade-off for these benefits is a longer operative time.

Introduction

Controversies exist regarding the management of rectal cancer with lateral pelvic node (LPN) involvement. In the West, it is considered a systemic disease, whereas in the eastern part of the world, it is considered a regional disease [1]. The West is managed with neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME) [1]. In the East, promising results have been demonstrated when LPN metastasis (LPNM) is treated with TME and LPN dissection (LPND) [1,2]. Furthermore, a recent collaborative multicenter LPN study concluded that TME with LPND decreased local recurrence in patients with suspected LPN metastases, even after preoperative chemoradiotherapy [3]. LPND is a challenging procedure due to its technical difficulties and the high risk of surgical morbidity. Despite this, LPND is widely performed using open and laparoscopic approaches [4]. A recent meta-analysis [4] concluded that laparoscopic LPND may be a better alternative to conventional open LPND for advanced rectal cancer with lower postoperative morbidity and shorter postoperative hospital stay. The laparoscopic approach poses challenges due to limitations such as a restricted field of vision, a flat 2-dimensional view of the narrow pelvis, and constrained dexterity. Robotic technologies have been employed to address these deficiencies. This technological advancement also presents opportunities to extend LPND. Despite the potential advantages, there is a scarcity of studies directly comparing the outcomes between Robotic Total Mesorectal Excision (RTME) with LPND and Laparoscopic Total Mesorectal Excision (LTME) with LPND, and the existing findings are inconsistent. By synthesizing the available evidence, this study endeavors to contribute to the highest level of evidence in the literature on this subject. Critical evaluation of postoperative outcomes will shed light on the comparative effectiveness and potential advantages of these two surgical approaches, offering valuable insights for clinical decision-making in the context of rectal cancer surgery.

This systematic review and meta-analysis aim to provide a comprehensive comparison of postoperative outcomes between RTME with LPND and LTME with LPND.

Methods

This study involved only human participants. This was a retrospective analysis of published cases that did not require informed consent. Ethical approval and consent to participate were not included in this review. The meta-analysis was conducted in accordance with the PRISMA 2020 (Preferred Reporting Items for Systematic Review and Meta-analysis) guidelines [5]. To evaluate its quality, we employed the AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews) 2 tool [6]. The study protocol was registered in PROSPERO under the identification number CRD42023403909.

Electronic database searches

We conducted a comprehensive electronic literature search through April 15, 2023, without language restrictions. The search encompassed multiple databases, including the Cochrane Library’s Controlled Trials Registry and Database of Systematic Reviews, PubMed/MEDLINE from the United States National Library of Medicine, Google Scholar, Excerpta Medica Database (Embase), and Scopus. The keywords employed in the search strategy were "Randomized Controlled Trials," "Clinical Controlled Trials," "lateral lymph nodes dissection," "total mesorectal excision," "rectal cancer," "robotic," "laparoscopy," "postoperative morbidity," "mortality," "outcomes," "overall survival," "disease-free survival," and "neoplasm recurrence." In addition, we manually reviewed the reference lists of the retrieved articles to identify relevant clinical trials.

Eligibility criteria

Studies: We included all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared robotic Total Mesorectal Excision (RTME) with Laparoscopic LPND, and laparoscopic Total Mesorectal Excision (LTME) with LPND. Non-comparative studies, editorials, letters to editors, review articles, and case series were excluded from analysis.

Population: This study focused on adults of any sex who underwent either RTME or LTME with LPND for advanced rectal cancer.

Intervention Group: Participants who underwent RTME with LPND for advanced rectal cancer were categorized into the R-LPND group.

Control Group: Patients who underwent LTME with LPND for advanced rectal cancer comprised the L-LPND group.

Outcomes: The primary outcome assessed was the morbidity rate, with secondary outcomes including anastomotic leak, intra-abdominal infection, urinary complications, operative time, hospital stay, number of Laparoscopic Pelvic Nodes (LPN) harvested, LPND time, overall recurrence, and local recurrence. Mortality and morbidity were considered when they occurred within 90 and 30 days after rectal resection, respectively.

Study Selection: Following independent literature searches conducted by two authors, all abstracts were independently reviewed. The inclusion criteria considered RCTs and CCTs were included in this study. The full texts of studies meeting these criteria were retrieved, and any disagreements were resolved through discussion with a third review team member.

Assessment of Study Quality and Risk of Bias: Two authors independently evaluated the selected studies based on predetermined criteria. Quality assessment for CCTs and RCTs used the Methodological Index of Non-Randomized Studies (MINORS) [7] and the Consolidated Standards of Reporting Trials (CONSORT) statement [8], respectively. Studies scoring below 13 on the MINORS or CONSORT scale were excluded because of fair quality. The risk of bias in RCTs was assessed using the Cochrane tool for bias assessment (RoB2) [9], whereas the risk of bias in CCTs was evaluated using the Newcastle Ottawa Scale (NOS) [10].

Missing Data: In instances of unclear bias domains or missing primary outcome information, the authors were contacted via email. If data were not numerically reported, information was extracted from the figures.

Handling Continuous Data: Continuous data were analyzed using the Review Manager 5.3.5 statistical package from the Cochrane collaboration for meta-analysis [11]. When the mean and standard deviation (SD) were not provided, they were estimated from the interquartile range (IQR) and median following the formula described by Hozo et al. [12].

Assessment of Heterogeneity: Heterogeneity was assessed using the Cochrane Chi² test (Q-test), I² statistic, and variance Tau² to estimate the degree of heterogeneity [13]. Funnel plots were used to identify studies responsible for heterogeneity, and subgroup analysis was conducted when all the included studies reported outcomes.

Summary of findings: Two authors independently evaluated the certainty of evidence using The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) [14]. The factors considered included study limitations, consistency of effect, imprecision, indirectness, and publication bias. The certainty of evidence was classified as high, moderate, low, or very low. Criteria for upgrading certainty included a large effect, dose-response gradient, and a plausible confounding effect. The Cochrane Handbook for Systematic Reviews of Interventions (sections 8.5 and 8.7, and chapters 11 and 12) and GRADEpro GDT software were utilized to prepare ’Summary of Findings’ tables, providing explanations for downgrading or upgrading certainty using footnotes with comments.

Evaluation of effect size: Meta-analysis was performed using the RevMan 5.3.5 statistical package from the Cochrane Collaboration [11]. The mean difference (MD) was selected as the effective measure for continuous data, whereas odds ratios (OR) with 95% confidence intervals (95% CI) were calculated for dichotomous variables. A random-effects model was applied, with a significance set at 0.05.

Results

Literature search results: Nine potentially relevant articles (Fig 1). We retained six eligible studies [2,15–19] and three studies were excluded for the following reasons: a systematic review and meta-analysis comparing open and laparoscopic LPND [4], one review article comparing laparoscopic and robotic LPND [20], and one non-comparative study [21]. The articles were published between 2018 and 2023. All of these studies were Asian: three studies from South Korea, two from Japan, and one from China. There have been no RCTs on this subject. These studies included 652 patients (316 patients with R-LPND and 336 patients with L-LPND) (Table 1). The demographic data of the included studies are summarized in Table 2. The mean ages ranged between 57 and 63 years in the R-LPND group and 58.3 and 63 years in the L-LPND group. The sex ratio was 1.68 with a male predominance. The BMI ranged between 21.1 kg/m² and 23.4 kg/m² in the R-LPND group and between 22.8 kg/m² and 23.8 kg/m² in the L-LPND group. Tumor height ranged from 4 to 5 cm in both groups. The tumor size ranged from 2.9 cm to 4.5 cm in the R-LPND group and 3.1 cm to 4.5 cm in the L-LPND group. The follow-up duration among the different studies ranged from one to 44.6 months.

Fig 1. Flow-diagram of the bibliographic research.

Fig 1

Open in a new tab

Table 1. List of the retained studies.

First author Country of origin Journal Year of publication Study period Study type Study design Number of patients* (Robo/Lap) Quality assessment
(MINORS)		 Risk of bias assessment (NOS)
Bae South Korea Biomedicines 2023 2015.2021 Retrospective comparative multicenter 34/74 20 6
Ishizaki Japan Techniques in Coloproctology 2023 2013–2022 Retrospective comparative monocentric 27/33 20 6
Kim South Korea Surgical Endoscopy 2018 2006–2014 Retrospective comparative monocentric 50/35 16 5
Morohashi Japan Surgical Endoscopy 2020 2014–2020 Retrospective comparative monocentric 40/55 18 6
Song South Korea Tech Coloproctol 2021 2006–2016 Retrospective comparative monocentric 70/29 18 6
Zhang China Surgical Endoscopy 2023 2015–2021 Retrospective comparative multicentric 95/110 20 6
Open in a new tab

Table 2. Demographic data of the different retained studies.

Studies Age (years)
Robo/Lap		 Gender (Male: female)
Robo/Lap		 BMI (mean, kg/m2)
Robo/Lap		 Rectal tumor location Tumor height (mean or median, cm) Robo/Lap ASA score
Robo/Lap		 Tumor size (mean or medium, cm)
Robo/Lap		 Nb LPND Follow-up (months)
Robo/Lap		 Neo-adjuvant therapy (%) Robo/Lap
Mid Low ≤2 >2 Bilateral Unilateral
Bae
 60/63 21:13/50:24 - 20/47 14/27 - 32/73 2/1 2.9 (0.5–4.0)/
3.1 (1.6–5.0)		 4/6 30/68 - 88.2/73
Ishizaki
 61/59 20:7/22:11 21.1/22.8 - - 4/4 27/32 0/1 4.4 (21–80)/
4.5 (11–85)		 - -
Kim
 57/60 29:20/21:15 23.4/23 14/14 36/21 4.4/5.2 46/33 4/2 - 10/6 40/29 22.1/28.3 82/68.6
Morohashi
 63/63 31:6/41:14 22.8/22.3 - - 5/5 - - 4 (0–6) / 4 (0–8) 33/55 - 94.1/78.2
Song
 57.5/60 46:24/24:5 22.7/22.8 19/9 51/20 4/4 66/28 4/1 - 16/4 54/25 44.6/39.8 87.1/82.8
Zhang
 60.4/58.3 54/74 22.4/23.8 - - 4.6/4.1 82/89 13/21 4.5 ±1.7/
4.4 ± 1.8		 47/43 48/67 - 38.9/40
Open in a new tab

Morbidity

The morbidity rate has been reported in six studies [2,15–19]. post-operative complications were reported in 77 of 316 patients in the R-LPND group and 130 of 336 patients in the L-LPND group. There was a lower morbidity rate in the R-LPND group than in the L-LPND group (OR = 0.52, 95%CI [0.34 to 0.79], p = 0.003] (Fig 2A) There was low heterogeneity among studies (Tau² = 0.08).

Fig 2. Forest plots of the postoperative outcomes.

Fig 2

Open in a new tab

A: Forest plot of the postoperative morbidity. B: Forest plot of the anastomotic leak. C: Forest plot of the intra-abdomlnal abscess. D: Forest plot of the urinary complications. E: Forest plot of the neurological complications. F: Forest plot of the operative time. G: Forest plot of the hospital stay.

Anastomotic leak

The anastomotic leak rate has been reported in six studies [2,15–19]. It was reported in 16 of 316 patients in the R-LPND group and in 27 of 336 patients in the L-LPND group. There was no significant difference between the two groups (OR = 0.74, 95%CI [0.36, 1.54], p = 0.42) (Fig 2B). There was low heterogeneity among studies (Tau² = 0.02).

Intra-abdominal infection

The intra-abdominal infection rate was reported in four studies [16–19]. It was reported in 11 of 255 patients in the R-LPND group and eight in of 229 patients in the L-LPND group. There was no significant difference between the two groups (OR = 0.132, 95%CI [0.5 to 3.47], p = 0.55) (Fig 2C).

Urinary complications

The urinary complication rate was reported in six studies [2,15–19]. It was reported in 26 of 316 patients in the R-LPND group and in 62 of 336 patients in the L-LPND group. There was a lower rate of urinary complications in the two R-LPND groups (OR = 0.39, 95%CI [0.24 to 0.64]; p = 0.0002) (Fig 2D).

Neurological complications

The neurological complication rate was reported in six studies [2,15–19]. It was reported in five out of 316 patients in the R-LPND group and 13 out of 336 patients in the L-LPND group. There was no significant difference between the two groups (OR = 0.47, 95%CI [0.18 to 1.22], p = 0.12) (Fig 2E).

Operative time

Five studies reported data on operative time [2,16–19]. It was reported in 289 patients in the R-LPND group and 303 patients in the L-LPND group. The operative time was longer in the R-LPND group (MD = 45.45, 95%CI [13.53 to 77.63], p = 0.005) (Fig 2F). There was high heterogeneity among the studies (Tau2 = 1011.96).

Hospital stay

Six studies reported hospital stay [2,15–19]. It was reported in 316 patients in the R-LPND group and 336 patients in the L-LPND group. A shorter hospital stay was observed in the R-LPND group (MD = -4.35, 95%CI [-6.49 − -2.20], p<0.001) (Fig 2G). There was low heterogeneity among studies (Tau2 = 4.76).

LPN dissected

Six studies reported the number of LPNs retrieved [2,15–19]. It was reported in 316 patients in the R-LPND group and 336 patients in the L-LPND group. There were a higher number of harvested lateral pelvic lymph nodes in the R-LPND group (MD = 1.75, 95%CI [0.35 to 3.15], p = 0.01) (Fig 3A). There was low heterogeneity among studies (Tau2 = 1.80).

Fig 3. Forest plots of the pathological findings.

Fig 3

Open in a new tab

A: Forest plot of the lateral pelvic nodes dissected. B: Forest plot of the lateral pelvic nodes dissection time.

LPND time

Three studies reported the LPND time [15,17,19]. It was reported in 162 patients in the R-LPND group and 198 patients in the L-LPND group. There was no significant difference between the two groups (MD = 1.01, 95%CI [-9.00 to 11.02], p = 0.84) (Fig 3B). Moderate heterogeneity was observed among the studies (Tau2 = 65.7).

Overall recurrence

This outcome has been reported in three studies [2,16,18]. It was reported in 46 of 154 patients in the R-LPND group and 38 of 138 patients in the L-LPND group. There was no significant difference between the two groups (OR = 0.87, 95%CI [0.45 to 1.68], P = 0.69) (Fig 4A). There was low heterogeneity among studies (Tau2 = 0.11).

Fig 4. Forest plots of the oncological outcomes.

Fig 4

Open in a new tab

A: Forest plot of the overall recurrence. B: Forest plot of the local recurrence.

Local recurrence

This outcome has been reported in three studies [2,16,18]. It was reported in 12 of 154 patients in the R-LPND group and 13 of 138 patients in the L-LPND group. There was no significant difference between the two groups (OR = 0.71, 95%CI [0.26 to 1.95], p = 0.50) (Fig 4B). There was low heterogeneity among studies (Tau2 = 0.03).

Quality assessment of the included studies and reporting of the effects of R-LPND

MINORS and NOS scores are presented in Table 1. A Summary of the evidence is presented in Table 3. This review showed that when LPND is performed using the robotic approach, compared to the laparoscopic approach:

Table 3. Summary of the retained studies.
Outcomes № of participants
(studies)
Follow-up		 Certainty of the evidence
(GRADE)		 Relative effect
(95% CI)		 Anticipated absolute effects
Risk with L-LPND Risk difference with R-LPND
Operative time 592 (5 CCTs) ⨁⨁◯◯
Lowa 		- - MD 45.45 higher
(13.53 higher to 77.36 higher)
Morbidity 652 (6 CCTs) ⨁⨁◯◯
Lowa,b 		OR 0.52
(0.34 to 0.79)		 387 per 1000 140 fewer per 1000
(210 fewer to 54 fewer)
Major complications 412 (3 CCTs) ⨁◯◯◯
Very lowa,b 		OR 1.13
(0.52 to 2.46)		 70 per 1000 8 more per 1000
(33 fewer to 87 more)
Anastomotic leak 652 (6 CCTs) ⨁◯◯◯
Very lowb 		OR 0.74
(0.36 to 1.54)		 80 per 1000 20 fewer per 1000
(50 fewer to 38 more)
Hospital stay 652 (6 CCTs) ⨁◯◯◯
Very lowa,b 		- - MD 4.35 lower
(6.49 lower to 2.2 lower)
Intraabdominal infection 484 (4 CCTs) ⨁◯◯◯
Very lowb 		OR 1.32
(0.50 to 3.47)		 35 per 1000 11 more per 1000
(17 fewer to 77 more)
Urinary complication 652 (6 CCTs) ⨁⨁◯◯
Lowb 		OR 0.39
(0.24 to 0.64)		 185 per 1000 103 fewer per 1000
(133 fewer to 58 fewer)
Neurological complications 652 (6 CCTs) ⨁◯◯◯
Very lowb 		OR 0.47
(0.18 to 1.22)		 39 per 1000 20 fewer per 1000
(31 fewer to 8 more)
LPND time 360 (3 CCTs) ⨁◯◯◯
Very lowa 		- - MD 1.01 higher
(9 lower to 11.02 higher)
LPN retrieved 652 (6 CCTs) ⨁⨁◯◯
Lowa 		- - MD 1.75 higher
(0.35 lower to 3.15 higher)
Overall recurrence 292 (3 CCTs) ⨁◯◯◯
Very lowa,b 		OR 0.87
(0.45 to 1.68)		 283 per 1000 27 fewer per 1000
(132 fewer to 116 more)
Local recurrence 292 (3 CCTs) ⨁◯◯◯
Very lowa,b 		OR 0.71
(0.26 to 1.95)		 94 per 1000 25 fewer per 1000
(68 fewer to 74 more)
Open in a new tab

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; MD: Mean difference; OR: Odds ratio.

GRADE Working Group grades of evidence.

High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.

Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.

Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Explanations.

a. Existing heterogeneity.

b. Small number of event.

  • It may reduce morbidity, lower urinary complications, shorter hospital stay, and higher number of harvested lateral pelvic lymph nodes with an increase in operative time.

  • We do not know if there were any differences between the two groups in terms of major complications, anastomotic leak, intra-abdominal infection, neurological complications, LPND time, overall recurrence, and local recurrence because the evidence was very uncertain.

Discussion

This systematic review and meta-analysis concluded that the R-LPND group was associated with lower morbidity, lower urinary complications, shorter hospital stay, and higher harvested lateral pelvic lymph nodes with longer operative time compared to the L-LPND group. There were no differences between the two groups in terms of major complications, anastomotic leak, intra-abdominal infection, neurological complications, LPND time, LPN retrieval, overall recurrence, and local recurrence.

The safety and feasibility of robotic rectal cancer surgery have been well established [22]. LPND in advanced rectal cancer has recently attracted additional attention because of its promising role in local recurrence and improving survival [3,23]. However, for LPND, many colorectal surgeons are still reluctant to perform this procedure using a minimally invasive approach because of its complexity and potential postoperative complications. For TME, robotic surgery has tended to overcome these difficulties with flexible instruments, quality 3D view, stable traction, and endowrists, allowing easier dissection in a deep and narrow pelvis. According to our results, robotics has overcome some of these difficulties with a significant reduction in overall morbidity [24].

Previous studies reported a lower anastomotic leak and intra-abdominal infection in the R-LPND group owing to the ease of incorporating indocyanine green fluorescence imaging [17]. Given the lack of significant differences between the two groups in our systematic review and meta-analysis, we conclude that R-LPND is at least as safe as L-LPND. Because LPND requires only lymphatic tissue dissection, the lateral pelvic vascular and nervous complexes should be preserved, as possible, during skeletonization. In some cases, we found a huge adhesion around the lymph nodes and we were obliged to scarify certain structures to ensure an oncological safe resection. Furthermore, excessive traction and trembling without direct damage to the major pelvic nerve plexus during dissection can cause urinary complications [25,26]. In our study, we concluded that the incidence of urinary complications was lower in the R-LPND group. Very stable traction and countertraction can cause less injury to the neuronal tissue. Several studies have reported a urinary dysfunction rate of 9.3%–16.7% after LPND [27,28]. This could be due to the resection of the inferior vesical vessels, which seems to increase postoperative urinary dysfunction [29]. Preserving the inferior vesical vessels reduces urinary dysfunction and spares the pelvic splanchnic trunk and plexus [29]. Yamaoka et al. [30], in a retrospective study of 337 patients undergoing TME, found in the multivariate analysis that the laparoscopic approach and open surgery were significantly associated with an increase in postoperative urinary dysfunction. They concluded that robot-assisted surgery was inversely correlated with postoperative early urinary dysfunction, and it may be a better approach to protect urinary function in lower rectal cancer surgery. Song et al. [18], In a retrospective study of 92 patients undergoing TME with selective LPND observed lower urinary retention in the R-LPND group than in the L-LPND group (7.1% vs. 24.1%; p = 0.043).

These findings are highly valuable given the complex anatomy of a region characterized by intricate networks of nerves and blood vessels. Despite comparable specific LPND times, the overall operative time was significantly longer in the R-LPND group than in the L-LPND group. According to this systematic review and meta-analysis, the laparoscopic procedure was 45 min shorter than the robotic procedure. We found high heterogeneity among the different studies when we focused on the mean operative time in the R-LPND group. It ranged between 260 min and 511.75 min. This could be explained by several factors, such as the absence of standardized criteria to measure this outcome and the unavailability of data regarding the learning curves of surgeons [31]. Kim et al. [16] demonstrated the experience of a single highly experienced surgeon. In contrast, Bae et al. [2] reported the experience of five different surgeons. Several studies have compared robotic and laparoscopic TME [32,33]. They reported longer operative times in the robotic surgery group. We believe that this difference could explain the difference between the R-LPND and L-LPND groups in our study because we did not find any difference between the two groups when we compared these two groups in terms of LPND time only. A shorter hospital stay is another additional advantage of the robotic approach. This outcome is essential in reducing infection risk, saving costs, and improving patient experience. However, this difference should be considered with caution in the absence of a clear statement regarding the application of an enhanced recovery protocol.

The retrieval of Laparoscopic Pelvic Nodes (LPN) is a crucial indicator of improved oncological outcomes [34]. Despite the absence of a consensus on the optimal number of harvested LPNs for evaluating pathological outcomes, the quantity retrieved often serves as a measure of the thoroughness of LPND. In our study, a noteworthy observation was the substantially higher number of LPNs harvested in the robotic group than in the laparoscopic group. This disparity in the number of retrieved LPNs can be attributed to two factors. First, the incorporation of fluorescence imaging with infrared optics into the robotic approach provides a distinct advantage. This technology facilitates the identification of metastatic lymph nodes during the robotic procedure, enhancing the surgeon’s ability to comprehensively harvest the nodes. Second, robotic en bloc resection of LN263P, LN 263D, and LN 283 using articulated instruments represents a technique that is challenging to replicate with laparoscopic forceps [15,35]. The superiority of the robotic approach in terms of retrieved LPN was not translated to the oncological data assessed in our study, and we found similar overall recurrence and local recurrence. It is worth mentioning that in our study, more patients in the robotic group received neoadjuvant therapy than those in the laparoscopic group. Unlike TME, cumulative evidence of the oncological safety of robotic LPND is scanty. Only three studies compared the recurrence rates between robotic and laparoscopic LPND. According to the results of a Japanese multicenter study [36] comparing TME with or without LPND, highlighting the reduced local recurrence rate after LPND (7% vs. 13%; p = 0.02), the comparison between robotic and laparoscopic LPND gradually became more critical.

This study had certain limitations that warrant careful consideration. The major limitation of the study is the lack of mature data and paucity of randomized trials, prospective studies, or propensity score matched studies which can control for confounding and selection bias. Additionally, the limited number of studies and participants coupled with missing data contributed to the overall constraints of the study. Notably, the inability to conduct a comparative analysis of the oncological outcomes represents another limitation. In addition, we should mention that all these studies were from Asian countries including patients with a low BMI and this highlighted the interest of additional non-Asian studies for an external validity of these findings. It is crucial to acknowledge that this study, being an inaugural systematic review and meta-analysis examining the two distinct approaches to LPND, may face inherent constraints due to the restricted availability of high-quality prospective studies in this domain.

In conclusion, the robotic approach is safe and feasible for TME with LPND for advanced rectal cancer. It ensures lower morbidity, especially lower urinary complications, with a shorter hospital stay and higher harvested LPN instead of a longer operative time. However, we strongly emphasized that the grade of evidence is low to very low across all measures of outcomes resulting in an inability to draw definite conclusions. Large, multicenter RCTs with longer follow-up would help validate the superiority in terms of morbidity and harvested LPN and will assess a better placement in oncological safety.

Supporting information

S1 Checklist. PRSIMA 2020 checklist.

(DOCX)

pone.0304031.s001.docx (32.2KB, docx)

Data Availability

All relevant data are within the article.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Otero de Pablos J, Mayol J. Controversies in the Management of Lateral Pelvic Lymph Nodes in Patients With Advanced Rectal Cancer: East or West? Front Surg [Internet]. 2020. [cité 24 juill 2023];6. Disponible sur: https://www.frontiersin.org/articles/10.3389/fsurg.2019.00079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Bae JH, Song J, Yoo RN, Kim JH, Kye BH, Lee IK, et al. Robotic Lateral Pelvic Lymph Node Dissection Could Harvest More Lateral Pelvic Lymph Nodes over Laparoscopic Approach for Mid-to-Low Rectal Cancer: A Multi-Institutional Retrospective Cohort Study. Biomedicines. 27 mai 2023;11(6):1556. doi: 10.3390/biomedicines11061556 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Ogura A, Konishi T, Cunningham C, Garcia-Aguilar J, Iversen H, Toda S, et al. Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer. J Clin Oncol. 1 janv 2019;37(1):33‑43. doi: 10.1200/JCO.18.00032 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Du R, Zhou J, Li D, Zhang Q, Liu J, Ma C, et al. Postoperative morbidity and mortality after mesorectal excision with laparoscopic versus conventional open lateral lymph node dissection for advanced rectal cancer: A meta-analysis. Asian J Surg. janv 2021;44(1):26‑35. doi: 10.1016/j.asjsur.2020.06.010 [DOI] [PubMed] [Google Scholar]
  • 5.Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 29 mars 2021;n160. doi: 10.1136/bmj.n160 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ. 21 sept 2017;j4008. doi: 10.1136/bmj.j4008 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (MINORS): development and validation of a new instrument. ANZ J Surg. 2003;73(9):712‑6. doi: 10.1046/j.1445-2197.2003.02748.x [DOI] [PubMed] [Google Scholar]
  • 8.Campbell MK, Elbourne DR, Altman DG. CONSORT statement: extension to cluster randomised trials. Bmj. 2004;328(7441):702‑8. doi: 10.1136/bmj.328.7441.702 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Yang ZR, Sun F, Zhan SY. Risk on bias assessment:(2) Revised Cochrane risk of bias tool for individually randomized, parallel group trials (RoB2. 0). Zhonghua Liu Xing Bing Xue Za Zhi Zhonghua Liuxingbingxue Zazhi. 2017;38(9):1285‑91. doi: 10.3760/cma.j.issn.0254-6450.2017.09.028 [DOI] [PubMed] [Google Scholar]
  • 10.Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ott Ott Hosp Res Inst. 2011;2(1):1‑12. [Google Scholar]
  • 11.Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions. 2008; [Google Scholar]
  • 12.Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5(1):1‑10. doi: 10.1186/1471-2288-5-13 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Borenstein M, Higgins JPT, Hedges LV, Rothstein HR. Basics of meta-analysis: I2 is not an absolute measure of heterogeneity. Res Synth Methods. mars 2017;8(1):5‑18. doi: 10.1002/jrsm.1230 [DOI] [PubMed] [Google Scholar]
  • 14.Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. avr 2011;64(4):401‑6. [DOI] [PubMed] [Google Scholar]
  • 15.Ishizaki T, Mazaki J, Kasahara K, Udo R, Tago T, Nagakawa Y. Robotic versus laparoscopic approach for minimally invasive lateral pelvic lymph node dissection of advanced lower rectal cancer: a retrospective study comparing short-term outcomes. Tech Coloproctology. juill 2023;27(7):579‑87. doi: 10.1007/s10151-023-02818-x [DOI] [PubMed] [Google Scholar]
  • 16.Kim HJ, Choi GS, Park JS, Park SY, Lee HJ, Woo IT, et al. Selective lateral pelvic lymph node dissection: a comparative study of the robotic versus laparoscopic approach. Surg Endosc. mai 2018;32(5):2466‑73. doi: 10.1007/s00464-017-5948-4 [DOI] [PubMed] [Google Scholar]
  • 17.Morohashi H, Sakamoto Y, Miura T, Kagiya T, Ogasawara K, Takahashi Y, et al. Short-term outcomes of robotic-assisted laparoscopic versus laparoscopic lateral lymph node dissection for advanced lower rectal cancer. Surg Endosc. sept 2021;35(9):5001‑8. doi: 10.1007/s00464-020-07979-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Song SH, Choi GS, Kim HJ, Park JS, Park SY, Lee SM, et al. Long-term clinical outcomes of total mesorectal excision and selective lateral pelvic lymph node dissection for advanced low rectal cancer: a comparative study of a robotic versus laparoscopic approach. Tech Coloproctology. avr 2021;25(4):413‑23. doi: 10.1007/s10151-020-02383-7 [DOI] [PubMed] [Google Scholar]
  • 19.Zhang L, Shi F, Hu C, Zhang Z, Liu J, Liu R, et al. Comparison of robotic versus laparoscopic lateral lymph node dissection for advanced lower rectal cancer: a retrospective study at two institutions. Surg Endosc. juin 2023;37(6):4403‑13. doi: 10.1007/s00464-023-09925-8 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Nakanishi R, Yamaguchi T, Akiyoshi T, Nagasaki T, Nagayama S, Mukai T, et al. Laparoscopic and robotic lateral lymph node dissection for rectal cancer. Surg Today. mars 2020;50(3):209‑16. doi: 10.1007/s00595-020-01958-z [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Park JA, Choi GS, Park JS, Park SY. Initial Clinical Experience with Robotic Lateral Pelvic Lymph Node Dissection for Advanced Rectal Cancer. J Korean Soc Coloproctology. oct 2012;28(5):265‑70. doi: 10.3393/jksc.2012.28.5.265 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Addison P, Agnew JL, Martz J. Robotic Colorectal Surgery. Surg Clin. 1 avr 2020;100(2):337‑60. doi: 10.1016/j.suc.2019.12.012 [DOI] [PubMed] [Google Scholar]
  • 23.Kim MJ, Chang GJ, Lim HK, Song MK, Park SC, Sohn DK, et al. Oncological impact of lateral lymph node dissection after preoperative chemoradiotherapy in patients with rectal cancer. Ann Surg Oncol. 2020;27:3525‑33. doi: 10.1245/s10434-020-08481-y [DOI] [PubMed] [Google Scholar]
  • 24.Feng Q, Yuan W, Li T, Tang B, Jia B, Zhou Y, et al. Robotic versus laparoscopic surgery for middle and low rectal cancer (REAL): short-term outcomes of a multicentre randomised controlled trial. Lancet Gastroenterol Hepatol. 2022;7(11):991‑1004. doi: 10.1016/S2468-1253(22)00248-5 [DOI] [PubMed] [Google Scholar]
  • 25.Sadakari Y, Hisano K, Sada M, Mizuuchi Y, Nagayoshi K, Fujita H, et al. Long-term effects of laparoscopic lateral pelvic lymph node dissection on urinary retention in rectal cancer. Surg Endosc. 1 févr 2022;36(2):999‑1007. doi: 10.1007/s00464-021-08364-7 [DOI] [PubMed] [Google Scholar]
  • 26.Emile SH, Elfeki H, Shalaby M, Sakr A, Kim NK. Outcome of lateral pelvic lymph node dissection with total mesorectal excision in treatment of rectal cancer: A systematic review and meta-analysis. Surgery. 1 mai 2021;169(5):1005‑15. doi: 10.1016/j.surg.2020.11.010 [DOI] [PubMed] [Google Scholar]
  • 27.Yamaguchi T, Konishi T, Kinugasa Y, Yamamoto S, Akiyoshi T, Okamura R, et al. Laparoscopic versus open lateral lymph node dissection for locally advanced low rectal cancer: a subgroup analysis of a large multicenter cohort study in Japan. Dis Colon Rectum. 2017;60(9):954‑64. doi: 10.1097/DCR.0000000000000843 [DOI] [PubMed] [Google Scholar]
  • 28.Park BK, Lee SJ, Hur BY, Kim MJ, Park SC, Chang HJ, et al. Feasibility of selective lateral node dissection based on magnetic resonance imaging in rectal cancer after preoperative chemoradiotherapy. J Surg Res. 2018;232:227‑33. doi: 10.1016/j.jss.2018.05.047 [DOI] [PubMed] [Google Scholar]
  • 29.Manabe T, Koga Y, Kubo H, Baba K, Nagayoshi K, Nagai S, et al. Adverse effects on the postoperative urinary function after combined resection of inferior vesical artery in laparoscopic lateral pelvic lymph node dissection: retrospective analysis of consecutive 95 series. Surg Laparosc Endosc Percutan Tech. 2019;29(6):493‑7. doi: 10.1097/SLE.0000000000000681 [DOI] [PubMed] [Google Scholar]
  • 30.Yamaoka Y, Kagawa H, Shiomi A, Yamakawa Y, Hino H, Manabe S, et al. Robotic-assisted surgery may be a useful approach to protect urinary function in the modern era of diverse surgical approaches for rectal cancer. Surg Endosc. 2021;35:1317‑23. doi: 10.1007/s00464-020-07509-4 [DOI] [PubMed] [Google Scholar]
  • 31.Flynn J, Larach JT, Kong JCH, Warrier SK, Heriot A. Robotic versus laparoscopic ileal pouch-anal anastomosis (IPAA): a systematic review and meta-analysis. Int J Colorectal Dis. juill 2021;36(7):1345‑56. doi: 10.1007/s00384-021-03868-z [DOI] [PubMed] [Google Scholar]
  • 32.Colombo PE, Bertrand MM, Alline M, Boulay E, Mourregot A, Carrère S, et al. Robotic Versus Laparoscopic Total Mesorectal Excision (TME) for Sphincter-Saving Surgery: Is There Any Difference in the Transanal TME Rectal Approach? Ann Surg Oncol. 1 mai 2016;23(5):1594‑600. [DOI] [PubMed] [Google Scholar]
  • 33.Prete FP, Pezzolla A, Prete F, Testini M, Marzaioli R, Patriti A, et al. Robotic Versus Laparoscopic Minimally Invasive Surgery for Rectal Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Ann Surg. juin 2018;267(6):1034. doi: 10.1097/SLA.0000000000002523 [DOI] [PubMed] [Google Scholar]
  • 34.Numata M, Tamagawa H, Kazama K, Kawahara S, Sawazaki S, Aoyama T, et al. Lateral lymph node dissection for mid-to-low rectal cancer: is it safe and effective in a practice-based cohort? BMC Surg. 21 janv 2021;21(1):51. doi: 10.1186/s12893-021-01053-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Kataoka K, Kanemitsu Y, Shiozawa M, Ikeda M. Lymph node classification in colorectal cancer: tumor node metastasis versus the Japanese system. In: The Lymphatic System in Colorectal Cancer. Elsevier; 2022. p. 107‑14. [Google Scholar]
  • 36.Fujita S, Mizusawa J, Kanemitsu Y, Ito M, Kinugasa Y, Komori K, et al. Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial. Ann Surg. août 2017;266(2):201. doi: 10.1097/SLA.0000000000002212 [DOI] [PubMed] [Google Scholar]

Decision Letter 0

Tsutomu Kumamoto

24 Mar 2024

PONE-D-24-01676Robotic Versus Laparoscopic Total Mesorectal Excision with Lateral Lymph Node Dissection for Advanced Rectal Cancer: A Systematic Review and Meta-AnalysisPLOS ONE

Dear Dr. Chaouch,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 08 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Tsutomu Kumamoto

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and 

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Additional Editor Comments:

The authors are conducting a very important review in rectal cancer surgery. However, there are several issues.

1. Regarding postoperative complications, more detailed descriptions are required for definitions and grades.

2. Will this review focus on both short-term and long-term results? It would be better to make a clear description of these.

3. There are no RCT or PS matching studies, and the review contains considerable selection bias. Considering this, the review must not mislead the readers.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors compared postoperative short course outcomes between robotic and laparoscopic TME+LPLND. The authors concluded that the robotic approach is a safe and feasible alternative in advanced rectal cancer. This is appealing to some physicians, but I have the following issues:

1. As described in discussion, the studies including in this analysis are all retrospective studies, which lead to selection bias.

2. The BMI of the cases is low (mean 21-23), so it should be described that this study is based on a biased case.

3. The definition of each complication is not stated. The grade of the complication should also be described.

4. There are many typographical errors.

Reviewer #2: This study is a meta-analysis conducted to investigate the advantages of robotic surgery over laparoscopic surgery in performing Lateral Pelvic Node Dissection (LPND). Appropriate studies were identified and analyzed. However, I would like to inquire about a few points:

1. The introduction states that while the benefits of postoperative outcomes are identified, the oncological safety has not been clarified. However, the abstract states that this study will clarify postoperative outcomes. If the objective is to compare short-term outcomes, the introduction in the text needs to be refined.

2. In the introduction, the citation for the following sentence needs to be corrected: "The overall risk of recurrence following this strategy increases from 10 (2) to 30% in cases of lateral node involvement (2)."

3. In the introduction, the citation for the following sentence needs to be replaced with a more appropriate one: "In the East, promising results have been demonstrated when LPN metastasis (LPNM) is treated with TME and Lateral Pelvic Node Dissection (LPND) (1)."

4. In the methods, the paragraph on eligibility criteria's studies needs clarification: "We included all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared robotic Total Mesorectal Excision (RTME) with Laparoscopic Pelvic Lymph Node Dissection (LPND), and laparoscopic Total Mesorectal Excision (LTME) with LPND." Please verify if the term 'laparoscopic pelvic lymph node dissection' is incorrectly written instead of 'lateral pelvic lymph node dissection.'

5. To analyze differences in anastomotic leakage, it would be beneficial to add the stoma rate to the results.

6. In the results, it would be advisable to include lymphocele, which is an LPND-specific complication.

7. Regarding the third paragraph of the discussion: "Because LPND requires only lymphatic tissue dissection, the lateral pelvic vascular and nervous complexes should be preserved during skeletonization." I disagree with this statement. I believe that if LPN has to be removed in proximity to certain structures, some vessels and nerves may need to be sacrificed. I would like to hear your opinion on this.

8. The use of abbreviations needs to be systematically reviewed throughout the text. Especially since LPN is described in the fifth paragraph of the discussion, it should have been detailed earlier. And as previously mentioned, the abbreviation "Laparoscopic Pelvic Lymph Node Dissection (LPND)" is inappropriate. There is a need for a clear review and arrangement of the abbreviations used throughout the text.

Reviewer #3: Thank you for the opportunity to review this study. My comments are as follows:

1. This review covers a relevant and interesting topic.

2. The introduction is rather wordy and covers many different concepts. This should be further summarised in shortened paragraphs to discuss the pertinent issues related to the topic at hand.

3. The statistical analysis appears to be sound and well conducted.

4. The major limitation of the study is the lack of mature data and paucity of randomized trials, prospective studies, or propensity score matched studies which can control for confounding and selection bias.

5. Several RCTs and meta-analyses already exist comparing Lap vs Robotic TME. The authors should decide if the study is to compare Lap TME + LPND vs RTME + LPND as currently is, or to focus on the Lap LPND vs Robotic LPND aspect – this is an important distinction as several important quality control and oncological parameters are missing should TME be included, such as rates of complete TME, distal resection margin, CRM positivity, and conversion rates. I suggest that the authors focus on the LPND aspect as this is relatively novel while there is an abundance of data on approaches to TME.

6. Table 2 is quite challenging to compare and interpret – I suggest there be an additional row demonstrating the pooled frequencies and proportions.

7. It should be strongly emphasized that the grade of evidence is low to very low across all measures of outcomes resulting in an inability to draw definite conclusions.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: review.pdf

pone.0304031.s002.pdf (64.7KB, pdf)
PLoS One. 2024 May 29;19(5):e0304031. doi: 10.1371/journal.pone.0304031.r002

Author response to Decision Letter 0

31 Mar 2024

Reviewer queries responses

Editor

Q1. Regarding postoperative complications, more detailed descriptions are required for definitions and grades.

R1. We have added that mortality and morbidity were considered when they occurred within 90 and 30 days after rectal resection, respectively.

Q2. Will this review focus on both short-term and long-term results? It would be better to make a clear description of these.

R2. We have removed the term “long-term” and we have used “oncological” results only to avoid this doubt.

Q3. There are no RCT or PS matching studies, and the review contains considerable selection bias. Considering this, the review must not mislead the readers.

R3. Thank you for this valuable remark. We have mentioned this detail in the limitation of the study, reported in the risk of bias assessment of the retained studies, and it was a reason to decrease the level of evidence of the different conclusions after the GRADE assessment in the summary of findings.

Reviewers

Reviewer #1:

Q1. As described in discussion, the studies including in this analysis are all retrospective studies, which lead to selection bias.

R1. Thank you for this valuable remark. We have mentioned this detail in the limitation of the study, reported in the risk of bias assessment of the retained studies, and it was a reason to decrease the level of evidence of the different conclusions after the GRADE assessment in the summary of findings.

Q2. The BMI of the cases is low (mean 21-23), so it should be described that this study is based on a biased case.

R2. Yes absolutely. We have also remarked on this point. However, it is explained by the origin of these studies from Asian countries that were well known with their low BMI. We have added this information in the discussion section and we have highlighted its interest for an external validity of our findings. Thank you for this remark.

Q3. The definition of each complication is not stated. The grade of the complication should also be described.

R3. We have added a definition of the different complications. Unfortunately, we cannot add additional information regarding the grade because it was not reported in the retained studies.

Q4. There are many typographical errors.

R4. We have corrected the different errors. Thank you

Reviewer #2:

Q1. The introduction states that while the benefits of postoperative outcomes are identified, the oncological safety has not been clarified. However, the abstract states that this study will clarify postoperative outcomes. If the objective is to compare short-term outcomes, the introduction in the text needs to be refined.

R1. We have removed this sentence from the introduction to alleviate this issue.

Q2. In the introduction, the citation for the following sentence needs to be corrected: "The overall risk of recurrence following this strategy increases from 10 (2) to 30% in cases of lateral node involvement (2)."

R2. We have corrected the references.

Q3. In the introduction, the citation for the following sentence needs to be replaced with a more appropriate one: "In the East, promising results have been demonstrated when LPN metastasis (LPNM) is treated with TME and Lateral Pelvic Node Dissection (LPND) (1)."

R3. We have added a reference to this sentence.

Q4. In the methods, the paragraph on eligibility criteria's studies needs clarification: "We included all randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared robotic Total Mesorectal Excision (RTME) with Laparoscopic Pelvic Lymph Node Dissection (LPND), and laparoscopic Total Mesorectal Excision (LTME) with LPND." Please verify if the term 'laparoscopic pelvic lymph node dissection' is incorrectly written instead of 'lateral pelvic lymph node dissection.'

R4. We have corrected it.

Q5. To analyze differences in anastomotic leakage, it would be beneficial to add the stoma rate to the results.

R5. Unfortunately, the stoma rate was not reported in the included studies.

Q6. In the results, it would be advisable to include lymphocele, which is an LPND-specific complication.

R6. This outcome was not reported in the different included studies.

Q7. Regarding the third paragraph of the discussion: "Because LPND requires only lymphatic tissue dissection, the lateral pelvic vascular and nervous complexes should be preserved during skeletonization." I disagree with this statement. I believe that if LPN has to be removed in proximity to certain structures, some vessels and nerves may need to be sacrificed. I would like to hear your opinion on this.

R7. Yes absolutely. In some cases, we found a huge adhesion of metastasis LN and we are obliged to scarify certain structures. We have added this information to this sentence.

Q8. The use of abbreviations needs to be systematically reviewed throughout the text. Especially since LPN is described in the fifth paragraph of the discussion, it should have been detailed earlier. And as previously mentioned, the abbreviation "Laparoscopic Pelvic Lymph Node Dissection (LPND)" is inappropriate. There is a need for a clear review and arrangement of the abbreviations used throughout the text.

Q9. We have reviewed all the abbreviations.

Reviewer #3:

Q1. The introduction is rather wordy and covers many different concepts. This should be further summarised in shortened paragraphs to discuss the pertinent issues related to the topic at hand.

R1. We have shortened the introduction.

Q2. The major limitation of the study is the lack of mature data and paucity of randomized trials, prospective studies, or propensity score matched studies which can control for confounding and selection bias.

R2. We have added this information in the limitations of our study.

Q3. Several RCTs and meta-analyses already exist comparing Lap vs Robotic TME. The authors should decide if the study is to compare Lap TME + LPND vs RTME + LPND as currently is, or to focus on the Lap LPND vs Robotic LPND aspect – this is an important distinction as several important quality control and oncological parameters are missing should TME be included, such as rates of complete TME, distal resection margin, CRM positivity, and conversion rates. I suggest that the authors focus on the LPND aspect as this is relatively novel while there is an abundance of data on approaches to TME.

R3. Thank you for this remark. At the beginning of our study, we performed literature research for all the studies comparing robotic and laparoscopic LPND. We have found studies of urology, digestive disease, and gynaecology. The most relevant issue was that the study population of the PICO that we used was very heterogeneous and it was impossible to pool the outcomes with a huge heterogeneity among the different studies in the majority of the outcomes. We thought that a focus only LPND is an excellent subject of a systematic review and not a meta-analysis.

Q4. It should be strongly emphasized that the grade of evidence is low to very low across all measures of outcomes resulting in an inability to draw definite conclusions.

R4. Yes, absolutely we have mentioned this information.

Attachment

Submitted filename: Reviewers queries responses.docx

pone.0304031.s003.docx (17.6KB, docx)

Decision Letter 1

Tsutomu Kumamoto

29 Apr 2024

PONE-D-24-01676R1Robotic Versus Laparoscopic Total Mesorectal Excision with Lateral Lymph Node Dissection for Advanced Rectal Cancer: A Systematic Review and Meta-AnalysisPLOS ONE

Dear Dr. Chaouch,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jun 13 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Tsutomu Kumamoto

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

The authors have addressed most of the reviewers’ comments. However, one reviewer has pointed out a few additional changes that should be made. We recommend reviewing the manuscript again.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: I Don't Know

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: You've worked hard on the revisions. I think your excellent research results have been sufficiently supplemented. I would like to make one request. It seems necessary to review all the citations in the discussion. There are minor issues such as some references having incorrect numbers or duplications. I recommend reviewing them once again.

Reviewer #3: =====================================================================================================All comments have been addressed

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Reviewer #3: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2024 May 29;19(5):e0304031. doi: 10.1371/journal.pone.0304031.r004

Author response to Decision Letter 1

1 May 2024

Reviewers’ queries responses

Reviewer #2:

You've worked hard on the revisions. I think your excellent research results have been sufficiently supplemented. I would like to make one request. It seems necessary to review all the citations in the discussion. There are minor issues such as some references having incorrect numbers or duplications. I recommend reviewing them once again.

Response :

Thank you for the remarks. We have checked all the references to avoid any issues.

Attachment

Submitted filename: Reviewers queries.docx

pone.0304031.s004.docx (13.1KB, docx)

Decision Letter 2

Tsutomu Kumamoto

6 May 2024

Robotic Versus Laparoscopic Total Mesorectal Excision with Lateral Lymph Node Dissection for Advanced Rectal Cancer: A Systematic Review and Meta-Analysis

PONE-D-24-01676R2

Dear Dr. Mohamed Ali Chaouch

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Tsutomu Kumamoto

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

This time, out of three reviewers, one reviewer gave a reject decision, and two reviewer gave a major revision. However, authors have addressed all the points indicated by the two reviewers. There are limitations, but it is a systematic review that will be useful for many colorectal cancer surgeons, and I decided to accept it.

Acceptance letter

Tsutomu Kumamoto

16 May 2024

PONE-D-24-01676R2

PLOS ONE

Dear Dr. Chaouch,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps.

Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

If we can help with anything else, please email us at customercare@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

M.D., Ph.D. Tsutomu Kumamoto

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Checklist. PRSIMA 2020 checklist.

    (DOCX)

    pone.0304031.s001.docx (32.2KB, docx)
    Attachment

    Submitted filename: review.pdf

    pone.0304031.s002.pdf (64.7KB, pdf)
    Attachment

    Submitted filename: Reviewers queries responses.docx

    pone.0304031.s003.docx (17.6KB, docx)
    Attachment

    Submitted filename: Reviewers queries.docx

    pone.0304031.s004.docx (13.1KB, docx)

    Data Availability Statement

    All relevant data are within the article.

    Articles from PLOS ONE are provided here courtesy of PLOS

    RESOURCES