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SYSTEMATIC REVIEW article

Front. Oncol., 12 June 2023
Sec. Surgical Oncology
This article is part of the Research Topic Effect of Minimally Invasive Interventional Therapy on Tumor Immune Microenvironment in Clinical Diagnosis and Treatment View all 5 articles

A systematic review and meta-analysis of minimally invasive total mesorectal excision versus transanal total mesorectal excision for mid and low rectal cancer

Du Yong GangDu Yong Gang1Lin Dong*Lin Dong2*Zhang DeChunZhang DeChun1Zhang YichiZhang Yichi1Lu YaLu Ya3
  • 1Department of Gastrointestinal Surgery, Pengzhou People's Hospital, Chengdu, Sichuan, China
  • 2Department of Urology, Pengzhou People's Hospital, Chengdu, Sichuan, China
  • 3Department of Respiratory Medicine, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China

Background: Minimally invasive total mesorectal excision (MiTME) and transanal total mesorectal excision (TaTME) are popular trends in mid and low rectal cancer. However, there is currently no systematic comparison between MiTME and TaTME of mid and low-rectal cancer. Therefore, we systematically study the perioperative and pathological outcomes of MiTME and TaTME in mid and low rectal cancer.

Methods: We have searched the Embase, Cochrane Library, PubMed, Medline, and Web of Science for articles on MiTME (robotic or laparoscopic total mesorectal excision) and TaTME (transanal total mesorectal excision). We calculated pooled standard mean difference (SMD), relative risk (RR), and 95% confidence intervals (CIs). The protocol for this review has been registered on PROSPERO (CRD42022374141).

Results: There are 11010 patients including 39 articles. Compared with TaTME, patients who underwent MiTME had no statistical difference in operation time (SMD -0.14; CI -0.31 to 0.33; I2=84.7%, P=0.116), estimated blood loss (SMD 0.05; CI -0.05 to 0.14; I2=48%, P=0.338), postoperative hospital stay (RR 0.08; CI -0.07 to 0.22; I2=0%, P=0.308), over complications (RR 0.98; CI 0.88 to 1.08; I2=25.4%, P=0.644), intraoperative complications (RR 0.94; CI 0.69 to 1.29; I2=31.1%, P=0.712), postoperative complications (RR 0.98; CI 0.87 to 1.11; I2=16.1%, P=0.789), anastomotic stenosis (RR 0.85; CI 0.73 to 0.98; I2=7.4%, P=0.564), wound infection (RR 1.08; CI 0.65 to 1.81; I2=1.9%, P=0.755), circumferential resection margin (RR 1.10; CI 0.91 to 1.34; I2=0%, P=0.322), distal resection margin (RR 1.49; CI 0.73 to 3.05; I2=0%, P=0.272), major low anterior resection syndrome (RR 0.93; CI 0.79 to 1.10; I2=0%, P=0.386), lymph node yield (SMD 0.06; CI -0.04 to 0.17; I2=39.6%, P=0.249), 2-year DFS rate (RR 0.99; CI 0.88 to 1.11; I2=0%, P = 0.816), 2-year OS rate (RR 1.00; CI 0.90 to 1.11; I2=0%, P = 0.969), distant metastasis rate (RR 0.47; CI 0.17 to 1.29; I2=0%, P = 0.143), and local recurrence rate (RR 1.49; CI 0.75 to 2.97; I2=0%, P = 0.250). However, patients who underwent MiTME had fewer anastomotic leak rates (SMD -0.38; CI -0.59 to -0.17; I2=19.0%, P<0.0001).

Conclusion: This study comprehensively and systematically evaluated the safety and efficacy of MiTME and TaTME in the treatment of mid to low-rectal cancer through meta-analysis. There is no difference between the two except for patients with MiTME who have a lower anastomotic leakage rate, which provides some evidence-based reference for clinical practice. Of course, in the future, more scientific and rigorous conclusions need to be drawn from multi-center RCT research.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022374141.

1 Introduction

Rectal cancer ranks third among the most common malignant tumors worldwide (1), and about 65% of rectal cancer is in the middle to low position. Total mesorectal excision (TME) is currently the standard surgical procedure for rectal cancer (2, 3). Some factors related to the recurrence, prolonged operation time (OP), and increased complications of rectal cancer have been identified, including male patients, pelvic stenosis, obese patients, and tumor size (4, 5). With the advancement of medical engineering technology, minimally invasive total mesorectal excision (MiTME) has gradually replaced open total mesorectal excision (OpTME) (6). Compared to OpTME, MiTME has a clear field of vision and a more precise operation process, which can obtain high-quality TME (7). However MiTME, especially in patients with difficult pelvic conditions, may not provide a clearer view and high-quality TME, and taTME has emerged, overcoming the drawbacks of previous MiTME techniques (8). There is currently a lack of meta-analysis that integrates laparoscopic and robotic versus transanal total mesorectal excision (TaTME). Therefore, the purpose of the meta-analysis is to analyze the perioperative, postoperative, and oncology outcomes of MiTME versus TaTME for mid and low rectal cancer.

2 Methods

2.1 Protocol and guidance

The study was performed according to Preferred Reporting Items for Systematic Reviews and the meta-analysis (PRISMA) (9) and the quality evaluation of this article was scored using the Newcastle-Ottawa Scale (NOS) score. The protocol for this review has been registered on PROSPERO (CRD42022374141).

2.2 Search strategy

This study involved literature published in the Embase, PubMed, Cochrane Library, Medline, and Web of Science up to September 18, 2022. We defined the eligibility criteria according to the population(P), intervention(I), comparator(C), outcome, and study design approach(O). P: The patients with mid and low rectal cancer. I: undergoing MiTME. C: TaTME was performed as a comparator. O: one or more of the following outcomes: perioperative period, postoperative indices, and oncologic outcomes. The search terms included (laparotomy OR laparoscopy OR laparoscopic OR minimally invasive OR robot OR robotic) AND (transanal OR perineal OR natural orifice) AND (colorectal cancer OR rectal cancer OR mesorectal excision OR TME OR proctectomy OR anterior resection OR abdominoperineal excision). The search strategy was not limited by language or year. The ethics or institutional review committee did not request it due to the study being designed as a systematic review and meta-analysis.

2.3 Inclusion and exclusion criteria

We have included the literature by the following criteria. Comparative data were available on the treatment of mid and low-rectal cancer through MiTME (RaTME and LaTME) and TaTME. Outcome indexes should include at least one of the following, perioperative period, postoperative indices, and oncologic outcomes. Any study which did not confirm the above inclusion criteria was excluded.

2.4 Data extraction and outcome measures

Two researchers (L.D. and Y.L.) independently reviewed the retrieved literature by the inclusion and exclusion criteria. The third researcher (Z.Y.C) was asked to participate in the discussion to decide whether to include when disagreements were encountered. The extracted data included the first author, publication, country, study type, group, age, follow-up, tumor height, and tumor size (if mentioned) (Table 1).

TABLE 1
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Table 1 The main characteristics of included studies.

2.5 Statistical analysis

Statistical analysis was performed by Stata v.12.0 (Stata Corp LLC, College Station, TX, USA). For this meta-analysis, if the heterogeneity test was I2>50%, P<0.1, we used the random effect model; if the heterogeneity test was I2<50%, P>0.1, we used the fixed utility model. The combined r values and 95% confidence intervals (CIs) of each study were calculated, and the forest map displayed the characteristics of each study result. The quality of the included literature was evaluated using the Newcastle–Ottawa scale (NOS). Begg’s and Egger’s tests were used to test the publication bias. The P<0.05 was indicated as statistically significant.

3 Results

3.1 Eligible studies and study characteristics

We initially searched 6059 records. 3376 literature that was published repeatedly and cross-published were deleted. After reading the title and abstract, 2399 articles were excluded. After the remaining 284 pieces of literature were searched for full text, reading, and quality assessment, 39 pieces of literature (11010 patients: MiTME: 6268 vs TaTME: 4742) were eventually included (Figure 1). The detailed information on this literature was listed in Table 1.

FIGURE 1
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Figure 1 Flowchart for records selection process of the meta-analysis. (According to PRISMA template: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal. Pmed 1000097).

3.2 Perioperative outcomes

Data on operation time (OP) were reported in 21 studies (6, 14, 15, 1721, 23, 25, 27, 30, 36, 38, 41, 4449). Compared with TaTME, patients who underwent MiTME had no statistical difference (SMD -0.00; CI -0.06 to 0.06; I2 = 84.7%, P=0.885). Owing to high heterogeneity (I2 = 84.7%), we chose subgroup analysis. Compared with TaTME, patients who underwent RoTME or LaTME had no statistical difference (SMD -0.03; CI -0.37 to 0.31; I2 = 82.5%, P=0.866; SMD -0.18; CI -0.40 to 0.04; I2 = 86.0%, P=0.102). Sensitivity analysis and subgroup analysis cannot reduce heterogeneity. Therefore, we choose random effect model results (SMD -0.14; CI -0.31 to 0.33; I2 = 84.7%, P=0.116) (Figure 2A). We included 11 studies (6, 14, 15, 17, 19, 23, 25, 30, 36, 38, 44) about estimated blood loss (EBL). Compared with TaTME, patients who underwent MiTME had no statistical difference (SMD 0.00; CI -0.09 to 0.09; I2 = 61.2%, P=0.955). Owing to high heterogeneity (I2 = 61.2%), sensitivity analysis was carried out by Stata 12.0. After removing the studies by Grass et al (19) and Ong et al (30) as the sample that was “left out”, the pooled results did not change substantially but the heterogeneity was significantly reduced (SMD 0.05; CI -0.05 to 0.14; I2 = 48%, P=0.338) (Figure 2B). Data on postoperative hospital stays were reported in 7 studies (14, 15, 17, 19, 23, 30, 44). Compared with TaTME, patients who underwent MiTME had no statistical difference (SMD 0.08; CI -0.07 to 0.22; I2 = 0%, P=0.308) (Figure 2C).

FIGURE 2
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Figure 2 Meta-analysis of minimally invasive total mesorectal excision vs transanal total mesorectal excision for mid and low rectal cancer in (A) operation time, (B) estimated blood loss (C) postoperative hospital stays (D) over complications, (E) intraoperative or postoperative complications, (F) anastomotic leak rates, (G) anastomotic stenosis, (H) wound infection.

Data on over complications were reported in 20 studies (1416, 1921, 23, 24, 26, 27, 29, 34, 41, 4345, 4951). Compared with TaTME, patients who underwent MiTME had no statistical difference (RR 0.98; CI 0.88 to 1.08; I2 = 25.4%, P=0.644) (Figure 2D). Compared with TaTME, patients who underwent MiTME had no statistical difference in intraoperative (RR 0.94; CI 0.69 to 1.29; I2 = 31.1%, P=0.712) (Figure 2E-1) or postoperative complications (RR 0.98; CI 0.87 to 1.11; I2 = 16.1%, P=0.789) (Figure 2E-2). Compared with TaTME, patients who underwent MiTME had less anastomotic leak rates (SMD -0.38; CI -0.59 to -0.17; I2 = 19.0%, P<0.0001) (Figure 2F), patients who underwent MiTME had no statistical difference in anastomotic stenosis (RR 0.85; CI 0.73 to 0.98; I2 = 7.4%, P=0.564) (Figure 2G), and patients who underwent MiTME had no statistical difference for wound infection (RR 1.08; CI 0.65 to 1.81; I2 = 1.9%, P=0.755) (Figure 2H).

3.3 Postoperative outcomes

Data on circumferential resection margin (CRM) were reported in 19 studies (1113, 16, 19, 2327, 31, 3638, 43, 44, 49). Compared with TaTME, patients who underwent MiTME had no statistical difference (RR 1.10; CI 0.91 to 1.34; I2 = 0%, P=0.322) (Figure 3A). Data on distal resection margin (DRM) were reported in 7 studies (24, 25, 27, 36, 38, 45, 46). Compared with TaTME, patients who underwent MiTME had no statistical difference (RR 1.49; CI 0.73 to 3.05; I2 = 0%, P=0.272) (Figure 3B). Data on major low anterior resection syndrome (LARS) were reported in 9 studies (12, 17, 19, 26, 28, 30, 34, 38, 50). Compared with TaTME, patients who underwent MiTME had no statistical difference (RR 0.93; CI 0.79 to 1.10; I2 = 0%, P=0.386) (Figure 3C). Data on lymph node yield were reported in 11 studies (14, 15, 19, 23, 24, 30, 36, 41, 43, 48, 49). Compared with TaTME, patients who underwent MiTME had no statistical difference (SMD 0.06; CI -0.04 to 0.17; I2 = 39.6%, P=0.249) (Figure 3D).

FIGURE 3
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Figure 3 Meta-analysis of minimally invasive total mesorectal excision vs transanal total mesorectal excision for mid and low rectal cancer in (A) circumferential resection margin, (B) distal resection margin, (C) major low anterior resection syndrome, and (D) lymph node yield.

3.4 Oncological outcomes

5 studies recorded on 2-year disease-free survival (DFS) rate (15, 25, 29, 43, 46), 5 studies recorded on 2-year overall survival (OS) rate (15, 25, 31, 43, 46), 3 studies recorded on distant metastasis (23, 31, 43), and 8 studies recorded on local recurrence (15, 23, 25, 29, 31, 43, 46, 48). There are similarities between MiTME and TaTME for the 2-year DFS rate (RR 0.99; CI 0.88 to 1.11; I2 = 0%, P = 0.816) (Figure 4A), 2-year OS rate (RR 1.00; CI 0.90 to 1.11; I2 = 0%, P = 0.969) (Figure 4B), distant metastasis rate (RR 0.47; CI 0.17 to 1.29; I2 = 0%, P = 0.143) (Figure 4C), and local recurrence rate (RR 1.49; CI 0.75 to 2.97; I2 = 0%, P = 0.250) (Figure 4D).

FIGURE 4
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Figure 4 Meta-analysis of minimally invasive total mesorectal excision vs transanal total mesorectal excision for mid and low rectal cancer in (A) 2-year DFS rate, (B) 2-year OS rate, (C) distant metastasis rate, and (D) local recurrence rate.

4 Publication bias

We conducted publication bias on more than 15 included studies using Begg’s test. For OP, Begg’s test results revealed that t=-1.87, P=.075 in Supplementary Figure 1A. For over complications. Begg’s test results revealed that t=0.81, P=.427 in Supplementary Figure 1B. For the circumferential resection margin, Begg’s test results revealed that t=4.20, P=.001 in Supplementary Figure 1C. There is no publication bias except circumferential resection margin in the above.

5 Discussion

As TaTME has reported more and more in recent years, so has its controversy (52). The main focus is on whether TaTME can get better safety and efficacy with mid to low-rectal cancer in patients. The results of this study show that patients who underwent MiTME had fewer anastomotic leak rates. Compared with TaTME, patients who underwent MiTME had no statistical difference in OP, EBL, postoperative hospital stay, over complications, intraoperative complications, postoperative complications, anastomotic stenosis, wound infection, CRM, DRM, major LARS, lymph node yield, 2-year DFS rate, 2-year OS rate, distant metastasis rate, and local recurrence rate. The absence of heterogeneity in postoperative hospital stays, circular differential recovery margin, total recovery margin, major low adverse recovery syndrome, 2-year disease-free survival, 2-year overall survival rate, distance metastasis rate, and local recurrence rate indicates that these results are reliable. The slightly lower heterogeneity of postoperative hospital stays, over applications, intra-operational applications, postoperative applications, analytical leak rates, analytical stenosis, and weak node yield indicates that these results are relatively reliable. The heterogeneity of EBL is slightly higher, which may be related to different surgeons. The high heterogeneity of OP indicates the low reliability of these results.

CRM positive rate is a good evaluation index for tumor outcome (53). This study’s results suggest no significant difference in the positive rate of CRM, DRM, lymph node yield between TaTME and MITME. This indicates that there is no difference in the treatment effectiveness between the two. In secondary outcomes, there is no significant difference between the two in terms of OP, EBL, postoperative hospital stays, CRM, DRM, LARS, lymph node yield, and incidence of intraoperative and postoperative complications. However, it is expected to achieve better results with the technique becomes more proficient in the application of mid and low rectal cancer (54). For oncological outcomes, only a small portion of studies have reported differences in late local recurrence and survival between the two groups. The Zeng (46) et al.’s study was found that the local recurrence rate was 3.8% in both groups of patients and another study confirmed that local recurrence is only 3% after TaTME for rectal cancer (55). However, our research results showed that there was no difference in DFS, OS, distance metastasis rate, and local recurrence rate between the two groups at 2 years. Currently, larger RCT studies are underway (56), and more reliable results are expected.

Both types of rectal cancer surgery have a certain impact on a patient’s quality of life (57), mainly LARS (58). A study suggests that some patients develop severe LARS after TaTME (59). Another article found a low incidence of mild/severe LARS in patients after TaTME (60). There was no significant difference in LARS between the two groups in this study. It shows that the probability of anal sphincter injury function damage is not increased after the anal operation of TaTME. This conclusion also adds a strong backing for the application of TaTME.

Of course, our research also has some limitations: 1. The included studies are retrospective studies or prospective cohort studies, which will inevitably be affected by selection bias. 2. In terms of the baseline report of the cases included in the literature, only some of them were provided. Of course, we analyzed the baseline data that can be extracted from the included literature, but we still lacked the comprehensiveness of the data, and could not conduct subgroup analysis according to general characteristics, such as male-female ratio, BMI value, etc. 3. In the data analysis, although we conducted a sensitivity analysis on highly heterogeneous outcome indicators, some results did not identify the source of their heterogeneity. 4. In terms of analysis indicators, the long-term efficacy, such as local tumor recurrence rate, was not analyzed by subgroup according to the follow-up time, while only 5 articles were included in the 2-year DFS and 2-year OS, and the number of articles included in the analysis was insufficient. 5. At present, the follow-up time of various studies is limited, and not enough long-term efficacy data is provided for analysis. In terms of functional outcome data, only kinds of literature mention it and it is not uniformly quantified, which causes certain difficulties in analysis.

6 Conclusion

This study comprehensively and systematically evaluated the safety and efficacy of MiTME and TaTME in the treatment of mid to low rectal cancer through meta-analysis. There is no difference between the two except for patients with MiTME who have a lower anastomotic leakage rate, which provides some evidence-based reference for clinical practice. Of course, in the future, more scientific and rigorous conclusions need to be drawn from multi-center RCT research.

Data availability statement

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.

Author contributions

Conceptualization: LD, ZD. Data curation: LD, LY, ZC. Formal analysis: LD, LY. All authors contributed to the article and approved the submitted version.

Funding

This work was supported by the Scientific Research Foundation of Health and Family Planning Commission of Chengdu (2022124) and the Scientific Research Foundation of Health and Family Planning Commission of Sichuan Province (20PJ236).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2023.1167200/full#supplementary-material

Supplementary Figure 1 | Egger's publication bias plot to detect publication bias.

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Keywords: minimally invasive total mesorectal excision, transanal total mesorectal excision, mid and low-rectal cancer, systematic review, meta-analysis

Citation: Gang DY, Dong L, DeChun Z, Yichi Z and Ya L (2023) A systematic review and meta-analysis of minimally invasive total mesorectal excision versus transanal total mesorectal excision for mid and low rectal cancer. Front. Oncol. 13:1167200. doi: 10.3389/fonc.2023.1167200

Received: 21 February 2023; Accepted: 10 May 2023;
Published: 12 June 2023.

Edited by:

Emanuele Damiano Urso, University of Padua, Italy

Reviewed by:

Ugo Grossi, University of Padua, Italy
Beatriz Martin-Perez, University Hospital of Badajoz, Spain

Copyright © 2023 Gang, Dong, DeChun, Yichi and Ya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Lin Dong, 913487290@qq.com

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