Clinical efficacy and safety of laparoscopic hybrid surgery for simultaneous resection of colorectal cancer liver metastases

Abstract

BACKGROUND

Simultaneous resection of colorectal cancer liver metastases (CRLM) has been widely adopted; however, clinical efficacy still varies across different surgical approaches, and the best surgical strategy remains controversial.

AIM

To investigate the efficacy and safety of laparoscopic hybrid surgery (LHS) vs total open surgery (TOS) the in simultaneous resection of CRLM.

METHODS

This was an observational study conducted at a tertiary medical center, enrolling 266 patients who undergoing simultaneous resection of CRLM from January 2017 to June 2021. The surgical approach was selected by colorectal surgeons and hepatobiliary surgeons based on their experience with either TOS or LHS. The primary outcomes were the incidence of complications, and postoperative recovery related outcomes. The secondary outcomes were 5-year overall survival and disease-free survival.

RESULTS

This study ultimately enrolled 144 patients in the LHS group and 122 patients in the TOS group. The complication rate was significantly lower in the LHS group than in the TOS group (10.4% vs 20.5%, P = 0.022). Compared with the TOS group, patients in the LHS group had shorter postoperative hospital stay [8.00 (6.00, 10.00) days vs 9.00 (8.00, 12.00) days, P < 0.001], earlier resumption of liquid intake [3.00 (3.00, 3.00) days vs 4.00 (3.00, 4.00) days, P < 0.001], and less intraoperative blood loss [300.00 (200.00, 400.00) mL vs 500.00 (500.00, 700.00) mL, P < 0.001]. However, the LHS group was associated with a longer operative time [260.00 (236.00, 320.00) minutes vs 240.00 (195.00, 269.00) minutes, P < 0.001]. No significant differences were observed in overall survival (P = 0.464) or disease-free survival (P = 0.838).

CONCLUSION

Compared with TOS, LHS for simultaneous resection of CRLM results in faster postoperative recovery, lower complication rates, and similar survival outcomes.

Key Words: Colorectal cancer; Colorectal cancer liver metastasis; Laparoscopic hybrid surgery; Simultaneous resection; Surgical approach

Core Tip: The best simultaneous resection strategy for patients with colorectal cancer liver metastases remains controversial. In this study, we innovatively propose a laparoscopic hybrid surgery (LHS) approach for simultaneous resection of colorectal cancer liver metastases. Compared with totally open surgery, the incidence of complications in the LHS group was significantly lower (10.4% vs 20.5%, P = 0.022). Patients treated with LHS had a shorter postoperative length of stay, earlier postoperative intake of liquids, less blood loss, and similar survival outcomes (overall survival, P = 0.464; disease-free survival, P = 0.838) to those treated with totally open surgery.

INTRODUCTION

Colorectal cancer (CRC) represents a solid gastrointestinal tract tumor with the third-highest incidence and second-highest mortality rate globally[1]. Being a common site for CRC metastasis, around 30%-50% of CRC patients will develop CRC liver metastases (CRLM) as the disease progresses[2,3]. Among these cases, approximately 50% of patients with CRLM develop liver metastases at or before the diagnosis of CRC, known as synchronous CRLM (SCRLM)[4].

The sole potentially curable approach to SCRLM is comprehensive radical resection of the primary and metastatic lesions[5]. Simultaneous resection of primary and metastatic lesions has been demonstrated to be safe and feasible, and associated with a substantial improvement in overall survival (OS), but it is not widely used in medical institutions around the world[6]. However, the adoption of simultaneous resection remains limited in many institutions worldwide, partly due to concerns regarding increased perioperative morbidity and the fact that not all patients are suitable candidates for this approach, as patient selection depends on factors such as overall medical condition, extent of liver involvement, and surgical risk tolerance. In addition, the choice of the synchronous resection surgical approach remains controversial. The totally open surgery (TOS) approach is characterized by increased invasiveness, prolonged patient recovery periods, and a potentially heightened risk of postoperative complications. In contrast, although laparoscopic surgery has been widely applied in the treatment of patients with CRC, with advantages such as shorter postoperative hospital stays and lower postoperative complication rates compared to open surgery[7,8], the fully laparoscopic approach is associated with longer procedures, increased technical complexity, and limited applicability[9]. Laparoscopic hybrid surgery (LHS), which blends minimal invasiveness with procedural simplicity, may therefore have greater application potential in this setting. Therefore, this study aimed to prospectively compare the short and long-term clinical efficacy of LHS vs TOS for the simultaneous resection of SCRLM. The study findings will hopefully provide recommendations for selecting optimal surgical approaches based on the varying preoperative condition of patients.

MATERIALS AND METHODS

Study design

This study was conducted at the Department of Colorectal Surgery, Shanghai Changhai Hospital. A dedicated database for patients undergoing simultaneous resection of CRLM was prospectively maintained, with enrollment and data collection initiated in January 2017. Patients were assigned to either the LHS cohort or the TOS cohort based on the surgical approach they received. This decision was made through a structured multidisciplinary team (MDT) discussion before surgery, involving senior specialists from colorectal surgery, hepatobiliary surgery, medical oncology, radiology, and pathology. The choice between LHS and TOS was guided by a comprehensive clinical assessment, considering factors such as the anatomical characteristics and distribution of liver metastases, the location and extent of the primary colorectal tumor, patient body habitus, comorbidities, and surgical team expertise, reflecting real-world clinical practice.

Patient data from January 2017 to June 2021 were included based on predefined criteria, and follow-up data collection was finalized in May 2024. For analysis, subgroups were stratified based on preoperative characteristics including age, gender, body mass index (BMI), primary tumor location, comorbidities, preoperative chemotherapy/targeted therapy, preoperative carcinoembryonic antigen/cancer antigen 19-9 levels, and KRAS/BRAF mutation status.

The primary outcome was the incidence of complications within 30 days post-surgery, graded using the Clavien-Dindo classification (grades I-II as minor, III-V as major). The postoperative complications observed in this study involved multiple systems, mainly gastrointestinal complications (such as bowel obstruction, anastomotic leakage, and abdominal infections), hepatic complications (such as bile leakage, subphrenic effusion, and liver dysfunction), respiratory complications (such as pleural effusion and respiratory dysfunction), cardiac complications (such as arrhythmia, acute coronary syndrome, heart failure, and cardiac arrest), and urinary complications (such as urinary tract infection and urinary retention), as well as general complications including hemorrhage and surgical site infection. Of these complications, anastomotic leakage was defined as a defect in the intestinal wall at the anastomotic site resulting in communication between the intestinal lumen and the extra-intestinal space, diagnosed based on clinical manifestations (such as peritonitis, purulent drainage from the drain or wound, fever accompanied by leukocytosis) or imaging findings [computed tomography (CT) or high-resolution magnetic resonance imaging (MRI)]. The remaining complications were diagnosed according to routine clinical diagnostic methods. Secondary outcomes were OS, defined as the time from surgery to death from any cause, and DFS, defined as the time from surgery to first recurrence or death from any cause.

Study population

The sample size calculation was performed using PASS software, with the incidence of complications serving as the primary outcome measure. Based on our center’s experience, the incidence of laparoscopic complications is approximately 10%, while that of open surgery is about 25%. Assuming a two-sided α of 0.05 and a power of 80% (β = 0.2), we estimated that a minimum of 121 subjects was needed for each cohort.

A total of 266 subjects were ultimately enrolled in the study, with 144 undergoing the LHS procedure and assigned to the LHS cohort, and 122 undergoing the TOS procedure and assigned to the TOS cohort. The inclusion criteria were as follows: (1) Detection of liver metastasis at the time of CRC diagnosis; and (2) Confirmation of both primary lesions and liver metastases through postoperative pathological examination. Exclusion criteria were: (1) Patients with unresectable extrahepatic metastases; (2) Patients with unresolved other malignancies; and (3) Incomplete clinical and pathological data or insufficient follow-up information.

Treatments

All patients were managed under a standardized protocol. Preoperative evaluation included tumor markers (carcinoembryonic antigen, cancer antigen 19-9), colonoscopy, abdominal imaging (CT/MRI), and positron emission tomography-CT if indicated. The final treatment plan, including the indication for neoadjuvant or conversion therapy for high-risk or initially unresectable disease, was ratified by the MDT.

The surgical procedure was performed simultaneously by experienced colorectal and hepatobiliary surgeons, with colorectal resection preceding liver surgery. The choice between LHS and TOS was determined jointly by colorectal and hepatobiliary surgeons based on comprehensive clinical assessment, taking into account multiple factors including: Tumor location (e.g., right colon vs rectum), extent and distribution of liver metastases (number, size, and segmental involvement), anticipated difficulty of pelvic dissection (e.g., due to obesity, prior pelvic surgery, or locally advanced disease), BMI, and presence of prior abdominal surgery that might affect adhesions or surgical access. In the LHS cohort, the colorectal phase (exploration, mobilization, vascular control, and bowel transection) was performed laparoscopically. In the TOS cohort, this phase was conducted via a midline laparotomy. In both cohorts, liver resection was subsequently performed via an open right subcostal incision. Hepatic inflow occlusion was applied as needed. Following liver resection and closure of the subcostal incision, intestinal anastomosis was completed (laparoscopically in LHS, via the open incision in TOS). An R0 resection was the objective, defined as microscopically negative margins.

Postoperative adjuvant chemotherapy was recommended for all patients according to institutional protocols, with the regimen and duration tailored to individual patient status. Follow-up included regular outpatient visits and telephone calls, with CT/MRI of the chest/abdomen/pelvis and tumor marker assessment every 3-6 months for the first 2 years, then every 6-12 months up to 5 years. Colonoscopy was scheduled at 1 year. Recurrence was managed via MDT discussion. Postoperative mortality was defined as any death during hospitalization or within 90 days of surgery.

Statistical analysis

Data analysis was performed using SPSS 26.0 (SPSS, Inc., Chicago, IL, United States), with statistical significance defined as two-tailed with a P value < 0.05. Normally distributed continuous variables are presented as mean ± SD, while non-normally distributed continuous variables are represented by median (interquartile range). Categorical variables were compared between cohorts using the χ² test or Fisher’s exact test (for non-normally distributed variables), while continuous variables were compared using the t-test or Wilcoxon Rank-Sum test (for non-normally distributed variables). Survival was evaluated using the Kaplan-Meier method with the log-rank test. The median follow-up time was calculated by the reverse Kaplan-Meier method.

RESULTS

Cohorts and baseline data

From January 2017 to June 2021, 144 patients were included in the LHS cohort, while 122 patients were included in the TOS cohort (Figure 1). There was no significant difference between the LHS cohort and the TOS cohort in terms of patient demographics. No significant differences were observed between the two groups in terms of demographic characteristics or baseline data (Table 1).

Figure 1 Study flowchart. SCRLM: Synchronous colorectal cancer liver metastases; TOS: Total open surgery; LHS: Laparoscopic hybrid surgery.

Table 1 Patient baseline data, n (%)/median (interquartile range).

Variable	TOS (n = 122)	LHS (n = 144)	P value
Gender			0.395
Male	70 (57.4)	90 (62.5)
Female	52 (42.6)	54 (37.5)
Age, years	60.00 (53.00, 67.00)	60.00 (51.25, 66.75)	0.813
Body mass index, kg/m2	23.44 (21.07, 25.36)	23.21 (21.49, 24.98)	0.943
Underlying conditions			0.570
Yes	72 (59.0)	80 (55.6)
No	50 (41.0)	64 (44.4)
Carcinoembryonic antigen at diagnosis, ng/mL			0.496
< 5	45 (36.9)	59 (41.0)
> 5	77 (47.5)	85 (59.0)
Cancer antigen 19-9 at diagnosis, U/mL			0.062
< 37	97 (79.5)	100 (69.4)
> 37	25 (20.5)	44 (30.6)
Preoperative chemotherapy			0.423
Yes	82 (67.2)	90 (62.5)
No	40 (30.8)	54 (37.5)
Preoperative targeted therapy			0.697
Yes	28 (23.0)	36 (25.0)
No	94 (77.0)	108 (75.0)
CRS score			0.289
1	34 (27.9)	50 (34.7)
2	53 (43.4)	57 (39.6)
3	31 (25.4)	33 (22.9)
4	4 (3.3)	4 (2.8)

TOS: Total open surgery; LHS: Laparoscopic hybrid surgery; CRS: Clinical Risk Score.

Pathological data

In terms of primary tumor characteristics, a higher proportion of patients undergoing LHS presented with rectal tumors (57.6%) and smaller maximum tumor sizes. Furthermore, a lower number of lymph nodes was identified in LHS-treated patients. In addition, there were no significant discrepancies observed between the two cohorts in terms of the number of resected metastases, tumor differentiation grade, pathological stage of the primary lesion, and gene mutation status (Table 2).

Table 2 Pathological data, n (%)/median (interquartile range).

Variable	TOS (n = 122)	LHS (n = 144)	P value
Tumor site			< 0.001
Right colon cancer	73 (59.8)	14 (9.7)
Left colon cancer	22 (18.0)	47 (32.6)
Rectal cancer	27 (10.2)	83 (57.6)
Maximum tumor size, cm
Primary lesion	4.00 (3.00, 6.00)	3.50 (2.50, 5.00)	0.003
Liver metastases	2.98 (1.57, 3.50)	2.98 (1.80, 3.00)	0.843
Differentiation of the primary lesion			0.677
Poor differentiation	28 (23.0)	30 (20.8)
Medium and high differentiation	94 (77.0)	114 (79.2)
Number of lymph nodes	16.00 (13.00, 19.00)	14.00 (11.00, 17.00)	0.001
Liver metastases number			0.936
< 3	113 (92.6)	133 (92.4)
> 3	9 (7.4)	11 (7.6)
pT stage			0.810
0-2	10 (8.2)	13 (9.0)
3-4	112 (91.8)	131 (91.0)
pN stage			0.736
0	45 (36.9)	47 (32.6)
1	54 (44.3)	70 (48.6)
2	23 (18.9)	27 (18.8)
KRAS gene			0.426
Wild-type	73 (59.8)	93 (64.6)
Mutant-type	49 (49.0)	51 (35.4)
BRAF gene			0.062
Wild-type	117 (95.9)	143 (99.3)
Mutant-type	5 (3.4)	1 (0.7)

TOS: Total open surgery; LHS: Laparoscopic hybrid surgery.

Complications within one month after surgery

The incidence of complications (based on the proportion of patients with at least one complication) in the LHS group was significantly lower than that in the TOS group (10.4% vs 20.5%, P = 0.022, Table 3). Specifically, complications were observed in 25 patients (20.5%) in the TOS cohort and 15 patients (10.4%) in the LHS cohort. The most common complications were gastrointestinal complications (including bowel obstruction, anastomotic leakage, and abdominal infections), respiratory complications (including pleural effusion and respiratory dysfunction), and general complications (including hemorrhage and surgical site infection). Overall, 14 patients reported serious complications (grade III/IV), with 8 (6.6%) in the TOS cohort and 6 (4.2%) in the LHS cohort. One patient (0.7%) in the LHS cohort underwent reoperation for anastomotic leakage. One patient (0.8%) in the TOS cohort died due to sepsis, liver failure, and gastrointestinal hemorrhage.

Table 3 Complications, n (%).

Variable	TOS (n = 122)	LHS (n = 144)	P value
Overall	25 (20.5)	15 (10.4)	0.022
Gastrointestinal complications
Bowel obstruction	1	1
Anastomotic leakage	7	10
Abdominal infections	1	1
Hepatic complications
Bile leakage	2	0
Subphrenic effusion	8	4
Liver dysfunction	2	2
Respiratory complications
Pleural effusion	15	12
Respiratory dysfunction	11	7
Cardiac complications (heart failure)	4	0
Urinary complications (urinary tract infection)	3	1
General complications
Hemorrhage	11	11
Surgical site infection	15	8
Clavien-Dindo grade I-II	17 (13.9)	9 (6.3)	0.141
Clavien-Dindo grade III-IV	8 (6.6)	6 (4.2)	0.919
Reoperation	0	1 (0.7)	0.356
Mortality	1 (0.8)	0	0.276

Complication subtypes are reported as total number of events; a single patient may have experienced multiple complications. TOS: Total open surgery; LHS: Laparoscopic hybrid surgery.

Operative findings and outcomes

In the LHS cohort, operative times were longer, while blood loss was significantly reduced compared with the TOS cohort. Both cohorts exhibited comparable rates of hepatic metastases resected with or without anatomical resection, as well as with or without portal vascular blockage. Patients in the LHS cohort had less blood loss [median (Q1, Q3), 300 (200.00, 400.00) mL vs 500 (500.00, 700.00) mL, P < 0.001], shorter postoperative length of stay [median (Q1, Q3), 8.00 (6.00, 10.00) days vs 9.50 (8.00, 12.00) days, P < 0.001], and earlier postoperative intake of liquids [median (Q1, Q3), 3.00 (3.00, 3.00) days vs 4.00 (3.00. 4.00) days, P < 0.001]. However, the total cost was higher [median (Q1, Q3), 66961.83 (60782.02, 74916.50) RMB vs 55533.20 (48,877.66, 64650.19) RMB, P < 0.001] in the LHS cohort (Table 4).

Table 4 Intraoperative and postoperative outcomes, median (Q1, Q3)/n (%).

Variable	TOS (n = 122)	LHS (n = 144)	P value
Operative time, minutes	240.00 (195.00, 269.00)	260.00 (236.00, 320.00)	< 0.001
Blood loss, mL	500.00 (500.00, 700.00)	300.00 (200.00, 400.00)	< 0.001
Anatomical liver resection			0.858
Yes	21 (17.2)	26 (18.1)
No	101 (82.8)	118 (81.9)
Hepatic portal blockade			0.227
Yes	63 (51.6)	85 (59.0)
No	59 (48.4)	59 (41.0)
Postoperative hospital stay, day	9.00 (8.00, 12.00)	8.00 (6.00, 10.00)	< 0.001
Time of liquid diet, day	4.00 (3.00, 4.00)	3.00 (3.00, 3.00)	< 0.001
Total hospital cost, RMB	55533.20 (48877.66, 64650.19)	66961.83 (60782.02, 74916.50)	< 0.001

TOS: Total open surgery; LHS: Laparoscopic hybrid surgery.

OS and DFS in the two cohorts

In the statistical analysis of OS, the endpoint event was observed in 44.4% of individuals in the LHS cohort and 53.3% in the TOS cohort, with no statistically significant difference noted (P = 0.46). The median OS for the two cohorts was 53.3 (44.1, 62.6) and 55.6 (48.1, 63.2) months, with a median follow-up of 55.6 (48.1, 63.2) and 42.6 (13.0, 69.1) months, respectively. Kaplan-Meier survival curves are depicted in Figure 2A. In addition, DFS was not statistically significant in either cohort (P = 0.84), with endpoint events occurring in 61.8% of subjects in the LHS cohort and 67.2% of subjects in the TOS cohort. The median DFS was 58.0 (42.7, 73.3) and 70.8 (65.4, 76.1) months for both cohorts, with median follow-up periods of 23.2 (19.9, 26.5) and 22.2 (17.5, 26.9) months, respectively. Kaplan-Meier survival curves are presented in Figure 2B.

Figure 2 Kaplan-Meier estimates of overall survival and disease-free survival stratified by surgical methods. A: Overall survival curves for the laparoscopic hybrid surgery cohort and the total open surgery cohort; B: Disease-free survival curves for the laparoscopic hybrid surgery cohort and the total open surgery cohort. OS: Overall survival; DFS: Disease-free survival; TOS: Total open surgery; LHS: Laparoscopic hybrid surgery.

Subgroup analyses of OS and DFS between the two cohorts

The subgroup analysis results are presented in Supplementary Figure 1. There was a significant interaction between the location of the primary tumor site and the surgical method on OS (P = 0.03). Specifically, patients with primary tumors such as rectal cancer demonstrated improved OS by undergoing LHS (hazard ratio: 0.525; 95% confidence interval: 0.290-0.949; P = 0.033). Consistent with these findings, the OS analysis within the primary tumor location subgroup corroborated this observation (Supplementary Figure 2). Other subgroup analyses including age, sex, BMI, basic disease, preoperative treatment, and gene mutation did not exhibit a significant interaction with OS or DFS, nor did they show a significant benefit in OS or DFS. In conclusion, this study demonstrates that compared with TOS, treatment with LHS for simultaneous resection of CRLM results in faster postoperative recovery, a significantly lower complication rate, and similar survival outcomes.

DISCUSSION

In this single-center study, we compared the clinical efficacy of LHS vs TOS for synchronous resection of CRLM. The study results showed that synchronous resection of the CRLM is safe and feasible, and LHS synchronous resection of CRLM was superior to TOS in terms of safety and short-term efficacy, and comparable to TOS in terms of long-term efficacy.

The results of our study suggest that the short-term prognosis of patients undergoing simultaneous resection by the LHS approach is better than that with TOS. Consistent with our findings, two previous studies[10,11] have shown that LHS procedures resulted in faster postoperative recovery, including earlier fluid intake and reduced postoperative hospitalization duration. Further analyses concluded that the patient’s postoperative recovery status mainly depended on the surgical approach to the bowel. This observation stems from the fact that recovery of the intestine, being a hollow viscus, exerts a more pronounced impact on the patient’s general condition. In contrast, the liver, being a substantial organ, may benefit from compensatory effects of other bodily components, thereby potentially mitigating local functional impairment. In alignment with prior research, the LHS cohort also had significantly less intra-operative bleeding than the TOS cohort, which was attributed to more delicate hemostatic maneuvers with laparoscopic surgery, including intra-operative ultrasonic knife hemostasis and the application of HEM-O-LOK tissue closure clips. The above results reflect the advantages of the LHS surgical approach in terms of short-term prognosis and hemorrhage control.

Additionally, LHS had a significantly lower incidence of complications compared to TOS, despite its longer surgical duration. A multicenter study evaluating 35 surgical procedures, including colorectal surgery, showed that prolonged operative time increased the incidence of complications[12]. Similarly, a comparative analysis between open and laparoscopic colectomy yielded analogous findings, indicating that operative durations exceeding 3 hours increased the rate of complications, especially in patients undergoing laparoscopic right hemicolectomy[13]. Another retrospective study showed that prolonged operative time increases the incidence of complications in patients undergoing colorectal resection, regardless of whether they undergo open, laparoscopic, or robotic surgery[14]. However, although our study showed that the surgical duration in the LHS group was significantly longer than that in the TOS group, the incidence of complications was significantly lower in the LHS group. Furthermore, the LHS cohort also had a lower rate of grade III/IV complications than the TOS cohort, despite the lack of statistical significance of the difference between these two cohorts. Therefore, it can be concluded that LHS has a higher safety profile compared to TOS.

Moreover, in the subgroup analysis stratified by primary tumor location (Supplementary Table 1), LHS was associated with a significantly lower complication rate in patients with rectal cancer compared with TOS (12.0% vs 37.0%, P = 0.003). Regarding postoperative hospital stay, LHS significantly reduced the length of stay in patients with left colon cancer (7.00 days vs 10.00 days, P = 0.004) and rectal cancer (8.00 days vs 12.00 days, P < 0.001), while a reduction in borderline statistical significance was also observed in patients with right colon cancer (7.50 days vs 9.00 days, P = 0.065). Additionally, the LHS group demonstrated significantly earlier resumption of a liquid diet in all three tumor locations (right colon: 3.00 days vs 4.00 days, P = 0.003; left colon: 3.00 days vs 4.00 days, P < 0.001; rectum: 3.00 days vs 4.00 days, P < 0.001). These findings collectively indicate that LHS confers consistent short-term advantages across different primary tumor locations, with the most pronounced benefits observed in rectal cancer patients. The universal improvement in postoperative recovery, particularly the uniformly accelerated return to liquid diet, underscores the minimally invasive nature of the hybrid approach and supports its broader applicability in the simultaneous resection of CRLM.

In terms of long-term outcome, there was no significant difference in OS and DFS between patients treated with LHS and TOS. A randomized controlled trial[15] investigating the variance in long-term oncologic outcomes between minimally invasive and open resection of CRLM yielded outcomes in accordance with our study findings. No significant difference in OS and recurrence-free survival (DFS in our study) was observed between the two surgical approaches. This finding underscores that the incorporation of minimally invasive techniques, combining open surgery with laparoscopy, represents a safe and viable surgical approach that does not introduce additional risks to the patient’s long-term prognosis.

Tumor size is a key determinant of T stage and is strongly correlated with both postoperative complications and oncologic outcomes. Notably, patients in the LHS group had smaller maximum tumor sizes compared with those in the TOS group. This difference may indicate that surgeons preferentially assigned patients with smaller tumor sizes to the LHS group, which underscores the consideration of oncological principles in surgical approach selection. Additionally, tumor size may be reduced by neoadjuvant therapy. With the evolution of treatment paradigms, the preoperative application of neoadjuvant therapy to achieve tumor downstaging represents a future trend, and the tumor size in surgical patients is correspondingly decreasing. This imbalance is an important consideration when interpreting the observed differences in complication rates and recovery outcomes between the two groups, and future studies with larger sample sizes are needed to perform subgroup analyses to determine the impact of this factor on patient prognosis. It is essential to acknowledge that long-term outcomes are influenced not only by the surgical technique but also by the preoperative adjuvant treatment strategies employed. In our center, LHS procedures and a MDT treatment approach were progressively implemented during the same period, which may have impacted long-term outcomes. Therefore, subgroup analyses were conducted to determine the potential influence of preoperative factors on long-term prognosis and to elucidate the subset of the population deriving long-term prognostic advantages from distinct surgical modalities. The results suggest that preoperative adjuvant or targeted therapies did not interact with the surgical method to affect the long-term prognosis of patients. Additionally, a notable improvement in OS was observed for patients with primary tumors, such as rectal cancer, who underwent LHS. Furthermore, patients were stratified based on the distance of the primary site in the rectum from the anal margin (n = 106, 4 patients with missing information). It was observed that patients with lower distances had a more significant OS benefit following LHS (Supplementary Figure 3). Within this subset, the occurrence of complications was lower in patients undergoing LHS compared to those undergoing TOS (Supplementary Table 2). These findings highlight the benefit of laparoscopic surgery, enabling precise maneuvering within a confined pelvic cavity. They also indicate that patients with SCRLM and primary lesions situated in the rectum could potentially derive advantages from the LHS approach. However, further elucidation is warranted to clarify the specific patient population that may benefit from the LHS procedure, necessitating comprehensive analyses of preoperative clinical data from a larger sample size[16].

In our study, the simultaneous resection of the primary tumor and liver metastases was performed using the COlon-LIver-COlon approach, which is consistent with the simultaneous resection method employed in the randomized controlled trial comparing simultaneous vs delayed resection for CRLM (METASYNC trial)[6]. Specifically, the procedure involves initial resection of the primary colorectal tumor (CO) without performing colonic/rectal anastomosis, followed by resection of the liver metastases (LI), and finally completion of the colonic/rectal anastomosis (CO)[17]. This sequence is primarily adopted because intraoperative events such as excessive bleeding may occur during liver resection, thereby affecting the surgical course. Moreover, the vasoconstrictors used to manage significant hemorrhage during liver surgery can compromise local perfusion at the anastomotic site. Additionally, the Pringle maneuver performed during liver resection may result in congestion of the anastomosis, thereby compromising the quality of the intestinal anastomosis. Therefore, the COlon-LIver-COlon approach effectively mitigates surgical risks and enhances surgical quality.

Advanced surgical techniques, including totally laparoscopic surgery (TLS) and robotic approaches for CRLM resection, have been extensively validated for safety and efficacy in both short- and long-term outcomes across multiple clinical studies[18,19]. However, the indications for these surgical approaches are relatively narrow for patients with a high number of liver metastases or complex liver tumor locations. This constraint not only adds to the scarcity of training opportunities for surgeons but also increases the learning curve associated with mastering these surgical techniques. In our center, full laparoscopic simultaneous resection is conducted; however, its application is confined to a limited set of criteria. Surgeons typically opt for this procedure in patients presenting with superficial liver metastases, limited metastatic foci, and small maximum diameters. In our recent practice, we have also accumulated experience with patients who underwent TLS. However, none of these patients have yet reached the 5-year follow-up endpoint comparable to the two cohorts in our study. Therefore, we compared short-term efficacy and safety between TLS and LHS (Supplementary Table 3). The LHS cohort had larger resected liver metastases, lower costs, and similar postoperative recovery times vs TLS. Importantly, TLS was associated with significantly higher complication rates, especially grade III or higher. These findings suggest that, given the current technical capabilities, LHS represents a preferable choice when taking into account multiple factors such as postoperative recovery, complication rates, and economic considerations.

This study has certain limitations. This is a single-center study, and validation of the findings in a randomized controlled trial is needed. In addition, although our study demonstrated that SCRLM patients with primary lesions located in the rectum undergoing resection by the LHS approach could achieve better OS benefit, we encountered challenges in establishing a comprehensive predictive model to forecast the long-term efficacy advantages of the LHS approach from the existing data. This limitation stems from incomplete preoperative information and the relatively small size of the patient cohort. The surgical approach was not randomly assigned but was determined by the treating surgeons based on a comprehensive clinical assessment. This non-randomized design introduces the possibility of selection bias, as patients with more complex diseases or higher surgical risk may have been preferentially allocated to the TOS group. Therefore, in our future studies, we plan to undertake randomized controlled trials encompassing larger sample sizes and incorporating a broader array of preoperative variables related to concurrent resection surgery in patients with SCRLM. This initiative aims to further corroborate the clinical utility of the LHS approach and to develop a diagnostic model predicting the long-term efficacy benefits of the LHS approach, thereby offering substantial clinical relevance.

CONCLUSION

LHS simultaneous resection of CRLM was associated with faster postoperative recovery and a lower incidence of complications compared with open surgery. Both cohorts demonstrated similar survival outcomes. Therefore, application of the LHS approach for the simultaneous resection of CRLM is safe and feasible. Subgroup analyses further indicated that selection of the LHS approach may lead to improved postoperative survival outcomes for patients with rectal cancer.

ACKNOWLEDGEMENTS

We sincerely thank our research team for their dedicated work. We are also grateful to all the study participants for their invaluable contribution.