Simple Summary: Colorectal cancer can be associated with liver metastasis and may be treated by minimal liver surgery using laparoscopic approaches and robotic surgery. Robotic surgery is of significant use in colorectal surgery and urology. However, there is still no long-term evidence concerning overall survival, and the number of patients operated on using this method remains small. Given the numerous benefits of robotic surgery and the concomitant small number of studies, we conducted a meta-analysis of the operative and short-term oncologic outcomes of laparoscopic versus robotic-assisted liver resection for colorectal liver metastases. The results of the meta-analysis show small differences in blood loss and conversion to open laparotomy rates in favor of robotic surgery. There were no differences in 30-day mortality, and there were also no differences in 1-year, 2-year, or 3-year mortality. The results indicate that both surgical methods are comparable in efficacy and safety. Colorectal cancer is the third most common cancer worldwide, and the liver is the most common localization of metastatic disease. The incidence of minimally invasive liver surgery is increasing, and robotic surgery (RLR) is believed to overcome some limitations of a laparoscopic approach (LRL). We performed a systematic review and meta-analysis of operative and short-term oncologic outcomes of the laparoscopic versus robotic-assisted liver resection for colorectal liver metastases. An online search of PubMed, Embase, Scopus, and the Cochrane databases was performed. Eight studies involving 3210 patients were considered eligible for the meta-analysis. In the LRL group, a higher conversion to open rate (12.4%) was observed compared to the RLR (6.7%; p = <0.001). 30-day mortality was 0.7% for the LRL group compared to 0.5% for the RLR group (p = 0.76). Mortality in longer periods among LLR and RLR amounted to 18.2% vs. 8.0% for 1-year mortality (p = 0.07), 34.1% vs. 26.7% for 2-year mortality (p = 0.13), and 52.3% vs. 48.3% for 3-year mortality (p = 0.46). The length of hospital stay was 5.6 ± 2.5 vs. 5.8 ± 2.1 days, respectively (p = 0.47). There were no significant differences between the incidence of individual complications in the LRL and RLR groups (p = 0.78). Laparoscopic or robotic approaches for colorectal liver metastases are comparable in terms of safety and effectiveness. There are significant advantages to robotic surgery, although there is still no long-term evidence concerning overall survival, and the number of patients operated on using RLR remains small.
Keywords: colorectal liver metastasis; liver cancer; robotic-assisted surgery; laparoscopic surgery; outcome
According to World Cancer Research Fund International, colorectal cancer is the third most common cancer worldwide. It is the third most common cancer in men and the second most common cancer in women [[
Surgery remains the mainstay of treatment for patients with colorectal metastases to the liver, and the incidence of the minimally invasive approach (MILS, Minimal Invasive Liver Surgery) has been increasing [[
While overall survival appears to be equal for both open surgery and laparoscopic approaches, the letter is associated with less morbidity, a shorter hospital stay, and fewer blood transfusions as a result of lower intraoperative blood loss and higher R0 resection rates. It is important to note that a long time of surgery for MILS was pointed out in a cited meta-analysis published by Xie et al. [[
Laparoscopic liver surgery is used in many centers, and the advantages of this method over open laparotomy are well-known; however, while laparoscopic liver surgery has had an established position in surgical armentaria, experience in the robotic approach to liver surgery still needs to be improved [[
Although reports about the robotic approach to liver surgery are not quite new [[
We now have substantial meta-analyses on the comparative results of robotic and laparoscopic hepatectomy that show that the outcome of operation time is relevant and robotics leads to longer operation time. There were no significant differences in blood transfusion rate, blood loss, conversion rate, length of hospital stay, or frequency of reoperation between the two groups- robotic and laparoscopic. However, none of these meta-analyses explicitly mentioned colorectal cancer hepatic metastases [[
The advantages of robotic-assisted surgery over laparoscopic surgery for colorectal liver metastases are still not fully known. As a result, the purpose of this meta-analysis was to compare the operative and short-term oncologic outcomes of laparoscopic vs. robotic-assisted liver resection for colorectal liver metastases.
This systematic review and meta-analysis were performed in accordance with the Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement [[
For data collection, we systematically searched PubMed, Embase, Scopus, and the Cochrane Library databases through December 2023, using the terms "robotic" or "robotic-assisted" AND "laparoscopic" AND "liver cancer" OR "liver metastases" AND "colorectal cancer" OR "colorectal liver metastasis surgery". We have performed searches using keywords (present in the title or abstract), combinations, and limits (humans, adults, and the English language). We have created a reference list, which we then screened. The search strategy was independently peer-reviewed by K.S. and M.P. If necessary, consensus-building or consultation with a third reviewer (L.S.) resolved all differences. Initial search results were merged and imported into the reference management software EndNote
We selected studies following our pre-specified clinical research question and the PICOS methodology: (
Two researchers (K.S. and L.S.) independently and separately extracted all the following information: first author name, year of publication, region of a cohort, patient characteristics (including the number of patients, age, and sex), intraoperative data (including the type of resection, Pringle maneuver, intraoperative blood loss, intraoperative transfusion, conversion to open laparotomy, operative time), pathological tumor data (including a number of metastases and the size of the largest metastases), or postoperative outcomes (survival rate, disease-free survival rate, length of hospital stay; adverse event types). Any concerns were agreed upon through discussion and analysis with a third researcher (J.S.). The acquired data were entered into a Microsoft Excel spreadsheet (Microsoft Corporation, Redmond, WA, USA) using a specially prepared form. In the absence of data on primary outcomes, we intended to contact the corresponding author of the original study.
We made comparisons of data regarding studies, results, study methodology, and design strengths and weaknesses. In each case, we evaluated the risk of bias using the Rob2 tool for randomized [[
The study's primary outcome was mortality outcomes, including in different follow-ups (from intraoperative to 3-year follow-up mortality). Other outcomes included length of hospital stay and morbidity occurrence.
Statistical analyses were performed using the Review Manager software (version 5.4, Nordic Cochrane Centre, Cochrane Collaboration) and Stata (version 14, StataCorp, College Station, TX, USA). All statistical tests were two-sided, and the significance level was defined as p < 0.05. We have used odds ratios (OR) as the effect measure with 95% confidence intervals (CIs) for dichotomous data and mean differences (MD) with 95% CI for continuous data. In this case, the continuous outcome was reported in a study as median, range, and interquartile range. We estimated means and standard deviations using the formula described by Hozo et al. [[
The study selection process is outlined in Figure 1. 533 records were identified in electronic databases. After duplicate removal, 317 records' titles and abstracts were screened by applying the inclusion and exclusion criteria described previously in the methods section. Fifteen potentially eligible articles were assessed for full-text evaluation. The final analysis included eight trials with a total number of 3210 patients [[
The detailed characteristics of the patients are presented in Table 2. The mean age of patients in the LLR and RLR groups was 63.5 ± 11.3 and 60.9 ± 10.6 years, respectively (MD = 1.21; 95%CI: 0.39 to 2.02; p = 0.004). Males predominated in both groups, with 59.4% in the LLR group and 60.9% in the RLR group, respectively (p = 0.49). There was no difference between LLR and RLR in prior abdominal surgery (70.6% vs. 64.9%; p = 0.80), prior chemotherapy (59.5% vs. 53.5%; p = 0.85), or liver cirrhosis (8.0% vs. 12.9%; p = 0.54).
The detailed characteristics of the data concerning the intraoperative period and tumor characteristics are presented in Table 3. Pooled analysis showed that the Pringle maneuver was performed statistically significantly more often in the LLR group compared to the RLR group (50.8% vs. 30.6%, respectively; OR = 3.33; 95%CI: 1.53 to 7.22; p = 0.002). Six studies reported intraoperative blood loss among the LRL and RRL groups. The pooled analysis showed that blood loss was higher in the LRL group compared to RRL (294.3 ± 312.0 vs. 190.8 ± 118.7 mL, respectively; MD = 178.68; 95%CI: 101.82 to 255.53; p < 0.001). More patients in the LRL group than the RLR group needed intraoperative transfusion (30.0% vs. 9.6% respectively; OR = 2.29; 95%CI: 0.79 to 6.63; p = 0.13). In the case of LRL, a statistically significantly higher conversion to open rate (12.4%) was observed compared to the RLR (6.7%; OR = 2.18; 95%CI: 1.46 to 3.24; p < 0.001).
30-day mortality was reported in three trials and was 0.7% for the LRL group compared to 0.5% for the RLR group (p = 0.76), while 90-day mortality was 1.3% vs. 0.0% respectively (p = 0.58, Supplementary Figure S4). Pooled analysis of 1-year mortality among LRL and RLR groups amounted to 18.2% vs. 8.0%, respectively (p = 0.07); in longer follow-up periods, significance disproportion was also not present: 2-year mortality (34.1% vs. 26.7%; p = 0.13); 3-year mortality (52.3% vs. 48.3%; p = 0.46). Length of hospital stay among LRL and RLR groups varied and amounted to 5.6 ± 2.5 vs. 5.8 ± 2.1 days, respectively (MD = 0.34; 95%CI: −0.59 to 1.28; p = 0.47). Table 4 presents a summary of the analyzed 30-day complications. There were no significant differences between the incidence of individual complications in the LRL and RLR groups (p > 0.05 for all complications).
Our meta-analysis included 3210 patients with colorectal metastases to the liver treated with surgery, either with a laparoscopic or robotic approach. Analyzed studies described MILS outcomes in patients with colorectal cancer metastases; we have not analyzed those describing primary hepatocellular carcinoma. This remark may be important while keeping in mind the results of previous abdominal surgery in the majority of patients with colorectal cancer (i.e., adhesions, previous chemotherapy, or additional synchronic procedures performed simultaneously at the bowel), which are absent in people with other non-metastatic malignancies localized in the liver.
Age was comparable in both groups, 63.5 ± 11.3 in the laparoscopic (LRL) group and 60.9 ± 10.6 in the robotic (RLR) group; males were the majority in both groups (59.4% and 60.9%, p = 0.49). There was no difference between LLR and RLR in prior abdominal surgery (70.6% vs. 64.9%; p = 0.80), prior chemotherapy (59.5% vs. 53.5%; p = 0.85), or liver cirrhosis (8.0% vs. 12.9%; p = 0.54). The LRL group's tumor size was more extensive: 4.92 ± 2.41 vs. 4.24 ± 1.8 cm (p = 0.008). 19.4% of the LRL underwent major liver resections compared to 16.2% in RLR (p = 0.008). Intraoperative blood loss was bigger in the laparoscopic group, 294.3 ± 312.0 mL, compared to 190.8 ± 118.7 mL in the robotic one, and intraoperative blood transfusions were noticeably more often in the first group (30.0% vs.' 9.6%, respectively; p < 0.001). Although the RLR group was associated with a higher transfusion rate in the postoperative period (11.7 vs. 6%, p = 0.05), the laparoscopic group received a higher number of packed red blood cells in a study published by Masetti [[
Operation time was comparable in both groups, 272.9 ± 97.4 and 247.9 ± 81.5 min, respectively (p < 0.001). Interesting RLR group characteristics provided a study of Beard: although more patients from this group underwent concomitant one-stage colon or rectal resections or amputations (62.6 vs. 35.2, p < 0.001), besides liver surgery, operation time remained equal [[
The length of hospital stay among LRL and RLR varied and amounted to 5.6 ± 2.5 and 5.8 ± 2.1 days (p = 0.47). Conversions to open surgery were more often with the laparoscopic approach (12.4% vs. 6.7%). Lack of positive resection margins (R1) was found more often in the laparoscopic group (22.5%) than in the robotic group (17.3%). Masetti et al. [[
There was no intraoperative mortality in both groups. The incidence of total postoperative complications was comparable at 22.4% and 21.9%, respectively, p = 0.78. Table 4 shows the details. It is worth noting that the incidence of the biliary fistula was observed at 2.5% in a laparoscopic group, with no cases reported in the robotic one, and bowel complications were present at 3.6% in the LCC group, indicating a lack of the problem shown in the RLR. On the contrary, one complication occurred more often in the RLR group than in the LRL group—a pleural effusion (4.3% vs. 2.8%, respectively; p = 0.23). Li et al., reporting the lower rate of complications in the RLR group in their study, explain the difference as an effect of a wider field of view, better positioning and surgical completion, and, thus, more precise operation [[
There is also a financial aspect to the robotic approach, which is higher than other options. However, looking at Beard's findings concerning the same operation time at synchronic bowel and liver resection mentioned above [[
Conclusions published by Beard et al. based on an analysis of results coming from six specialized, high-patient volume centers show the safety of the robotic approach. The authors indicate two conditions necessary for effectiveness and safety: experience with specialized hepatobiliary surgeons and previous experience with conventional laparoscopy [[
Study limitations. The robotic approach to liver metastases is relatively new, and the presented experience comes from highly experienced centers [[
Laparoscopic or robotic approaches for colorectal liver metastases are comparable in terms of safety and effectiveness. There are some significant advantages to robotic surgery, although there is still no long-term evidence concerning overall survival, and the number of patients operated on using RLR remains small. Larger randomized controlled trials comparing both methods are needed.
DIAGRAM: Figure 1 Flow diagram of the search strategy and study selection.
Table 1 Characteristics of included trials.
Study Country Study Design LLR Group RLR Group No. of Patients Age Sex, Male No. of Patients Age Sex, Male Balzano et al., 2023 [ Italy Prospective 192 66 ± 12 110 (57.3%) 77 66 ± 12.1 49 (63.6%) Beard et al. 2020 [ Multi-country Retrospective 514 63 ± 12 314 (61.2%) 115 61 ±11 39 (33.9%) Cheung et al., 2023 [ Multi-country Retrospective 219 55 ± 4.3 105 73 53.5 ± 4.3 34 Gumbs et al., 2022 [ Multi-country Retrospective 462 63.8 ± 11.7 259 (56.1%) 36 61.8 ± 11.0 21 (58.3%) Li et al., 2022 [ China Randomized 61 57.51 ± 6.27 38 (62.30%) 61 57.13 ± 586 44 (72.13%) Masetti et al., 2022 [ Italy Retrospective 953 65.6 ± 10.9 589 (62.7%) 77 65.0 ± 10.6 50 (64.9%) Radomski et al., 2023 [ USA Retrospective 266 52 NS 79 63 NS Rahimli et al., 2020 [ Germany Retrospective 13 62.1 ± 12.6 10 (76.9%) 12 63.5 ± 11.3 6 (50.0%)
Table 2 Baseline patient characteristics among included trials.
Outcome No. of Studies Event/Participants Events Heterogeneity LLR RLR OR or MD 95%CI I2 Statistics Sex, male 7 1383/2330 270/443 0.92 0.74 to 1.15 0.22 28% 0.49 Age, years 7 63.5 ± 11.3 60.9 ± 10.6 1.21 0.39 to 2.02 0.87 0% 0.004 BMI 6 25.97 ± 4.37 26.11 ± 5.66 −0.49 −1.11 to 0.13 0.04 58% 0.12 Prior 6 1602/2269 248/382 0.97 0.74 to 1.26 0.36 9% 0.80 Prior 4 575/966 115/215 0.97 0.70 to 1.34 0.82 0% 0.85 Liver cirrhosis 2 48/597 13/101 0.70 0.22 to 2.19 0.12 58% 0.54 Preoperative CEA 2 260.2 ± 162.5 61.62 ± 206.2 73.51 −290.02 to 437.004 0.002 90% 0.69
Table 3 Baseline characteristics of intraoperative parameters among included trials.
Outcome No. of Studies Event/Participants Events Heterogeneity LLR RLR OR or MD 95%CI I2 Statistics Major 3 261/1344 19/117 1.15 0.29 to 4.47 0.008 79% 0.84 Minor 3 1078/1344 98/117 0.86 0.21 to 3.47 0.006 80% 0.83 Pringle 4 881/1735 78/255 3.33 1.53 to 7.22 0.002 79% 0.002 Tumor size 4 3.94± 2.37 4.01 ± 1.82 0.03 −0.56 to 0.63 0.005 76% 0.91 Intraoperative blood loss (mL) 6 294.3 ± 312.0 190.8 ± 118.7 178.68 101.82 to 255.53 <0.001 99% <0.001 Intraoperative transfusion 5 568/1891 34/354 2.29 0.79 to 6.63 <0.001 82% 0.13 Conversion to open 6 312/2522 30/449 2.18 1.46 to 3.24 0.76 0% <0.001 R1 resection 4 328/1457 39/225 1.32 0.70 to 2.46 0.16 42% 0.39 Operative time, min 7 272.9 ± 97.4 247.9 ± 81.5 21.50 −5.28 to 48.28 <0.001 97% 0.12
Table 4 Polled analysis of outcomes among included trials.
Outcome No. of Studies Event/Participants Events Heterogeneity LLR RLR OR or MD 95%CI I2 Mortality Intraoperative 1 0/953 0/77 NE NE NA NA NA 30-day 2 13/1931 2/372 (0.5%) 1.23 0.32 to 4.83 0.66 0% 0.76 90-day 5 10/789 0/178 1.78 0.23 to 14.03 0.35 0% 0.58 1-year 3 32/176 14/176 2.56 0.94 to 6.98 0.15 53% 0.07 2-years 2 60/176 47/176 1.42 0.90 to 2.24 0.69 0% 0.13 3-years 2 92/176 (52.3%) 85/176 (48.3%) 1.17 0.77 to 1.78 0.56 0% 0.46 Hospital length of stay, days 7 5.6 ± 2.5 5.8 ± 2.1 0.34 −0.59 to 1.28 <0.001 99% 0.47 30-days complications Total 7 404/1806 106/482 1.04 0.81 to 1.32 0.25 26% 0.78 Major 7 167/2123 (7.9%) 28/449 (6.2%) 1.37 0.91 to 2.08 0.31 17% 0.13 Ascites 1 7/953 0/77 1.23 0.07 to 21.71 NA NA 0.89 Haemorrhage 2 19/1014 0/138 3.06 0.37 to 25.50 1.00 0% 0.30 Coagulopathy 1 4/953 0/77 0.73 0.04 to 13.77 NA NA 0.84 Biliary fistula 2 25/1014 0/138 4.45 0.56 to 35.20 0.89 0% 0.16 Bowel 1 34/953 0/77 5.82 0.35 to 95.77 NA NA 0.22 Surgical site infection 1 17/953 1/77 1.38 0.18 to 10.51 NA NA 0.76 Intra-abdominal abscess 2 32/1014 3/138 1.39 0.40 to 4.84 0.72 0% 0.60 Pneumonia 1 19/953 2/77 0.76 0.17 to 3.34 NA NA 0.72 Pleural effusion 2 28/1014 6/138 0.62 0.15 to 2.55 0.22 34% 0.50 Pneumothorax 1 2/953 0/77 0.41 0.02 to 8.56 NA NA 0.56 Deep vein thrombosis 1 2/953 0/77 0.41 0.02 to 8.56 NA NA 0.56 Pulmonary embolism 1 1/953 0/77 0.24 0.01 to 6.04 NA NA 0.39 Posthepatectomy liver failure 1 5/953 0/77 0.90 0.05 to 16.41 NA NA 0.94 30-d readmission 4 49/598 16/267 1.39 0.76 to 2.56 0.46 0% 0.29 30-d reoperation 4 18/600 4/267 1.72 0.61 to 4.87 0.57 0% 0.31
Conceptualization, K.S. and L.S.; methodology, K.S. and L.S.; software, K.S., M.J. and M.D.; validation, K.S., R.T. and L.S.; formal analysis, K.S. and L.S.; investigation, K.S., L.S., M.P. (Michal Pruc), M.J. and M.D.; resources, K.S. and L.S.; data curation, K.S., M.P. (Michal Pruc), L.S. and J.S.; writing—original draft preparation, K.S., R.T., M.P. (Michal Pruc) and L.S.; writing—review and editing, K.S., M.P. (Michal Pedziwiatr), M.P. (Michal Pruc), R.T., M.J., M.D., J.S., K.A., P.S., K.K. and L.S.; visualization, K.S., L.S. and K.A.; supervision, K.S. and L.S.; project administration, K.S., M.J. and M.D. All authors have read and agreed to the published version of the manuscript.
The data that support the findings of this study are available on request from the corresponding author (L.S.).
Author M.P. (Michal Pruc), P.S., K.K. and L.S. are from Department of Clinical Research and Development, LUXMED Group. The remaining 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.
The study was supported by the ERC Research Net and by the Polish Society of Disaster Medicine.
The following supporting information can be downloaded at: https://
By Kamil Safiejko; Michal Pedziwiatr; Michal Pruc; Radoslaw Tarkowski; Marcin Juchimiuk; Marian Domurat; Jacek Smereka; Khikmat Anvarov; Przemyslaw Sielicki; Krzysztof Kurek and Lukasz Szarpak
Reported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author