Prognostic impact of primary tumor site on liver metastasis in resectable colorectal cancer

doi:10.21203/rs.3.rs-3228205/v1

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Research Article

Prognostic impact of primary tumor site on liver metastasis in resectable colorectal cancer

https://doi.org/10.21203/rs.3.rs-3228205/v1

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Purpose

Currently, right colon cancer (RCC), left colon cancer (LCC), and rectal cancer (REC) are typically considered as different tumor entities when discussed. The curative effect and different prognoses of patients with colorectal liver metastases (CRLM) whom underwent simultaneous radical surgery are studied based on the site of the primary tumor.

Methods

This study analyzed 215 patients with CRLM at the First Affiliated Hospital of Sun Yat-sen University and were treated with radical surgery from 2008 to 2021. All data were analyzed by SPSS.

Results

Ratio of right colon liver metastasis (RCLM) of longitudinal diameter of primary tumor ≥ 5cm was more than left colon liver metastasis (LCLM) and rectal cancer liver metastasis (ReCLM) (61.0% versus 34.3% versus 33.3%, p = 0.001), and similarly for Percentage circumference of intestinal wall involved=1 (74.6% versus 57.8% versus 50.0%, p = 0.021).The three-year overall survival (OS) of RCLM group was significantly less than LCLM group and ReCLM group (37.5% versus 64.7% versus 62.5%, p = 0.016). The univariate and Multivariate analysis showed Percentage circumference of intestinal wall involved, lymph node metastasis and CA199 were the independent risk factors for OS of RCLM, and Percentage circumference of intestinal wall involved and CA199 were the independent risk factors for DFS of CRLM.

Conclusion

Primary tumors should be considered when analyzing the outcomes of CRLM.

Colorectal Liver Metastases (CRLM)

Surgery

Prognosis

Tumor site

Colorectal cancer (CRC)

Colorectal cancer (CRC) is the third most common cancer worldwide and is ranked second in terms of cancer-related mortality (1). It is estimated that the number of colorectal cancer cases worldwide will increase to 3.2 million new cases and 1.6 million deaths by 2040 (2). The liver is the most common site of metastasis for patients with CRC, and 15–25% of patients are found with liver metastases at the time of diagnosis (3). Based on the location of the primary tumor, CRC generally falls into three types: right colon cancer (RCC), left colon cancer (LCC), and rectal cancer (REC). Embryologically, the right half of our colon derives from the embryonic midgut and is bounded by the splenic flexure, while the left half and rectum derive from the hindgut (4–6). Due to the differences in origin and microenvironment, there are different clinical manifestations, pathological patterns, molecular markers, prognosis, mode of tumor metastasis, and treatments between the RCC, LCC and REC. In consequence, many studies have shown that there were different prognosis owing to different locations of primary tumor in recent years (7–10). However, there is no definitive conclusion whether the prognosis is different for patients with colorectal liver metastases (CRLM) whom underwent simultaneous radical surgery as a result of different primary tumor sites (11–13). This study compared curative effect of radical operation in patients with CRLM, based on the primary tumor location.

Patients

The institutional review board approved this study, which abided by the revised Declaration of Helsinki and the requirements of good clinical practice.

We retrospectively analyzed data from 215 patients with CRLM treated with simultaneous radical surgery from 2008 to 2021. The hepatectomy for CRLM were oligo-hepatic metastasis, the metastasis can be resected by preoperative assessment and residual liver is expected to be compensatory, and primary surgical resection of liver metastases without preoperative contraindications. Diagnosis of CRLM includes colonoscopy with pathology report, abdominal and pelvic CT, PET-CT, and elevated digestive tract tumor markers from colonoscope. The treatment plan was determined by a multi-disciplinary team (MDT) consisting of professionals from departments such as gastrointestinal surgery, oncology, hepatological surgery, radiology, intervention radiology, nutrition, rehabilitation, etc. Simultaneous radical surgery was defined as total resection of the primary lesion along with the surrounding lymph node metastases, and resection of the liver metastases with normal liver tissue within 1cm of the incisal margin and no hilar lymph node enlargement in the patient.

Right colon cancer (RCC) included ascending colon cancer and cancer of hepatic flexure of colon, and left colorectal cancer (LCC) included cancer of splenic flexure of colon, cancer of descending colon, sigmoid colon cancer and rectal cancer. In addition, well differentiated means high differentiation, medium-high differentiation and medium-low differentiation, and poorly differentiated means medium-low differentiation, low differentiated and undifferentiation. This study was approved by the Medical Ethics Committee of the Seventh Affiliated Hospital of Sun Yat-sen University (No.KY-2023-053-01). Individual consent for this retrospective analysis was waived.

Follow-up

The information collected included patient characteristics, characteristics of primary tumor, operative indications, tumor marker, postoperative pathological staging, postoperative complications, postoperative gastrointestinal function recovery, and features of liver metastases. Overall survival (OS) was defined as the time from radical surgery to death or last follow-up; and relapse-free survival was recorded from the time of radical surgery to death or new metastasis or recurrence. The follow-up data were retrieved from clinical data, phone interviews, and readmission records, if available. The patients were monitored with abdominal CT per 1 to 2 months after surgery and periodic review afterwards.

Statistical analysis

Patients were divided into three groups based on the site of the primary tumor. The RCLM group was composed of all patients with cancer of the cecum, ascending colon and hepatic flexure section of transverse colon. The LCLM group consisted of patients with cancer of splenic flexure section of transverse colon, descending colon and sigmoid colon. Finally, the ReCLM group was made up of rectal cancer patients. To evaluate the differences in clinicopathological characteristics and short- and long- term clinical outcomes of the three, ANOVA test was used. Values of p < 0.05 were regarded as statistically significant. Long-term outcomes and survival curves were analyzed using the Kaplan-Meier method. Logistic regression analysis was used to analyse the risk factors. Values of p < 0.1 were regarded as statistically significant. All analyses were performed using BM SPSS statistics 25.0 software (Chicago, IL, USA).

Study cohort characteristics

In total, 215 patients were included in this study (Fig. 1), including 59 (27.4%) RCLM patients, 102 (47.5%) LCLM patients, and 54 (25.1%) ReCLM patients. Table 1 sums up the clinicopathological characteristics of the study cohort by group. There are not statistically significant including sex (p = 0.572), age (p = 0.937), Body Mass Index (BMI) (p = 0.425), number of liver metastases (p = 0.792), differentiation (p = 0.624), pT stage (p = 0.805), pN stage (p = 0.714), lymph node metastasis (p = 0.834), neoadjuvant chemotherapy (p = 0.971), CEA>5ng/ml (p = 0.253), CEA>200ng/ml (p = 0.307), CA-125>40ng/ml (p = 0.194) and complications (p = 0.410). In terms of the ratio of longitudinal diameter of primary tumor ≥ 5cm for RCLM was more than those in LCLM and ReCLM (RCLM group: 61.0% vs. LCLM group: 34.3% vs. ReCLM group: 33.3%; p = 0.001). Moreover, the ratio of Percentage circumference of intestinal wall involved (=1) in the RCLM group was also more than that of LCLM and ReCLM groups (RCLM group: 74.6% vs. LCLM group: 57.8% vs. ReCLM group: 50.0%, p = 0.021). The incidence of CA-199>40ng/ml was greater in LCLM group than in the other groups (RCLM group: 8.4% vs. LCLM group: 20.5% vs. ReCLM group: 6.0%; p = 0.042). In addition, the further analysis found that the result of the inter-group analysis about the Percentage circumference of intestinal wall involved included that the group of RCLM was more than LCLM (RCLM group: 74.6% vs. LCLM group: 57.8%, p = 0.036), the group of RCLM was more than ReCLM (RCLM group: 74.6% vs. ReCLM group: 50.0%, p = 0.008) and the group of ReCLM was indistinction for LCLM (LCLM group: 57.8% vs. ReCLM group: 50.0%, p = 0.336). The incidence of complications was well illustrated in Fig. 3a (Percentage of total complications). The most common was intra-abdominal infection (36%), followed by stomal fistula (18%), pulmonary infection (15%), incision infection (8%), bile fistula (8%), intestinal obstruction (5%) and others.

CRLM treated with surgery (2008–2021): n = 566

Exclusion criteria: palliative surgery, liver biopsy, and asynchronous resection

Final count: RCLM…..

Table 1

Clinicopathological characteristics of patients with CRLM
	All	RCLM (%)	LCLM (%)	ReCLM (%)	p value
n	215	59 (27.4%)	102 (47.5%)	54 (25.1%)
Sex					0.572
Male	151 (70.2%)	40 (18.6%)	70 (32.6%)	41 (19.1%)
Female	64 (29.8%)	19 (8.8%)	32 (14.9%)	13 (6.0%)
Age(years) ≥ 60	110 (51.2%)	29 (13.5%)	53 (24.7%)	28 (13.0%)	0.937
BMI (nomal)	145 (67.4%)	40 (67.8%)	65 (63.7%)	40 (74.1%)	0.425
Longitudinal diameter of primary tumor (≥ 5cm)	89 (41.4%)	36 (61.0%)	35 (34.3%)	18 (33.3%)	0.001
Percentage circumference of intestinal wall involved(=1)	130 (60.5%)	44 (74.6%)	59 (57.8%)	27 (50.0%)	0.021
		44 (74.6%)	59 (57.8%)		0.036
		44 (74.6%)		27 (50%)	0.008
			59 (57.8%)	27 (50%)	0.336
Number of liver metastases (>1)	80 (37.2%)	23 (40.0%)	39 (38.2%)	18 (33.3%)	0.792
Differentiation (well)
Well	204 (94.9%)	57 (96.6%)	97 (95.1%)	50 (92.6%)	0.624
Poorly	11 (5.1%)	2 (3.4%)	5 (4.9%)	4 (7.4%)
pT stage (pT0-pT3)	87 (40.5%)	26 (44.1%)	40 (39.2%)	21 (38.9%)	0.805
pT0	2 (0.9%)	0 (0%)	1 (0.5%)	1 (0.5%)
pT1	8 (3.6%)	3 (1.4%)	1 (0.5%)	4 (1.9%)
pT2	8 (3.7%)	4 (1.9%)	0	4 (1.9%)
pT3	69 (32.1%)	23 (10.7%)	34 (15.8%)	12 (5.6%)
PT4	128 (59.5%)	33 (15.3%)	62 (28.8%)	33 (15.3%)
pN stage					0.714
pN0	70 (32.6%)	21 (9.8%)	30 (14.0%)	19 (8.8%)
pN1	90 (41.9%)	25 (11.6%)	46 (21.4%)	19 (8.8%)
pN2	55 (25.6%)	13 (6.0%)	26 (12.1%)	16 (7.5%)
Lymph node metastasis					0.834
Yes	146 (67.9%)	39 (18.1%)	72 (33.5%)	35 (16.3%)
No	69 (32.1%)	20 (9.3%)	30 (14.0%)	19 (8.8%)
Neoadjuvant chemotherapy					0.971
Yes	50 (23.3%)	13 (6.0%)	24 (11.2%)	13 (6.0%)
No	165 (76.7%)	46 (21.4%)	78 (36.3%)	41 (19.0%)
CEA
>5ng/ml	136 (63.3%)	36 (16.7%)	70 (32.6%)	30 (14.0%)	0.253
≤ 5ng/ml	79 (36.7%)	23 (10.7%)	32 (14.9%)	24 (11.2%)
>200ng/ml	12 (5.6%)	5 (2.3%)	6 (2.8%)	1 (0.5%)	0.307
≤ 200ng/ml	203 (94.4%)	54 (25.1%)	96 (44.7%)	53 (24.7%)
CA125
>40ng/ml	20 (9.3%)	8 (3.7%)	10 (4.7%)	2 (0.9%)	0.194
≤ 40ng/ml	195 (90.7%)	51 (23.7%)	92 (42.8%)	52 (24.2%)
CA199
>40ng/ml	75 (34.9%)	18 (8.4%)	44 (20.5%)	13 (6.0%)	0.042
≤ 40ng/ml	140 (65.1%)	41 (19.1%)	58 (27.0%)	41 (19.1%)
Complications					0.410
Yes	36 (16.7)	9 (4.2%)	15 (7.3%)	12 (5.6%)
No	179 (83.3%)	50 (23.3%)	87 (40.5%)	44 (20.5%)

Long-term outcomes

The survival analysis of patients was very clearly as shown in Table 2. The median follow-up periods were as follows: RCLM group: 46 months, LCLM group: 47 months and ReCLM group: 60 months. The three-year

Number of included patients
	RCLM	LCLM	ReCLM	P value
Overall Survival (OS)	40	68	32	0.016

OS was significantly different between those three groups (RCLM group: 37.5% vs. LCLM group: 64.7% vs. ReCLM group 62.5%; p = 0.016), and the median survival time for RCLM, LCLM, and ReCLM groups were 24 months, 36 months and 35 months respectively, and the result could be nicely represented by this survival curve (Fig. 2). Moreover, the results of intra-group analysis were as follows (RCLM group: 37.5% vs. LCLM group: 64.7%, p = 0.006; RCLM group: 37.5% vs. ReCLM group: 62.5%, p = 0.032; LCLM group: 64.7% vs. ReCLM group: 62.5%, p = 0.883). However, the three-year DFS and five-year OS and DFS were insignificantly different among the three groups (three-year DFS: RCLM group: 35.0% vs. LCLM group: 39.7% vs. ReCLM group 37.5%; p = 0.889; five-year OS: RCLM group: 27.3% vs. LCLM group: 43.6% vs. ReCLM group 38.1%; p = 0.461; five-year DFS: RCLM group: 27.3% vs. LCLM group: 20.5% vs. ReCLM group 33.3%; p = 0.553). The incidence of relapse or metastases was well illustrated in Fig. 3b (Percentage of total recurrence or metastasis). The most common one was liver metastases (53%), followed by pulmonary metastasis (18%), relapse (7%), liver and lung metastasis (7%), brain metastasis (2%), bone metastasis (2%), adrenal metastasis (2%) and so on.

Table 2

Long-term survival analysis of CRLM
	All	RCLM	LCLM	RECLM	P value
Three-year survival analysis (n)	140	40	68	32
OS of rate	56.4%	37.5%	64.7%	62.5%	0.016
		37.5%	64.7%		0.006
		37.5%		62.5%	0.032
			64.7%	62.5%	0.883
Median survival time (months)		24	36	35
DFS of rate	37.9%	35.0%	39.7%	37.5%	0.889
Five-year survival analysis (n)	82	22	39	21
OS of rate	37.8%	27.3%	43.6%	38.1%	0.461
DFS of rate	25.6%	27.3%	20.5%	33.3%	0.553

Risk factors of OS and DFS

Table 3 shows the results of univariate and multivariate analyses of factors affecting OS in patients with LCLM. The result of univariate analysis showed that the Percentage circumference of intestinal wall involved (p = 0.048) was the risk factor for the overall survival in patients of LCLM.

Table 3

Univariate and multivariate analyses of factors affecting Overall survival in patients of LCLM
Variable	Univariate		Multivariate
	HR (95% CI)	P value	HR (95% CI)	P value
Sex (Male)	0.952 (0.340–2.667)	0.926
Age (≥ 60)	0.705 (0.260–1.914)	0.493
BMI (nomal)	0.481 (0.160–1.450)	0.194
Longitudinal diameter of primary tumor (≥ 5cm)	0.587 (0.208–1.658)	0.315
Percentage circumference of intestinal wall involved(=1)	0.289 (0.084–0.989)	0.048
Number of liver metastases (>1)	1.018 (0.341–3.038)	0.974
Differentiation (Well)		0.999
pT0-pT3 stage	0.506 (0.159–1.632)	0.256
Lymph node metastasis (yes)	1.192 (0.410–3.468)	0.747
CEA (ng/ml)
>5ng/ml	0.628 (0.193–2.040)	0.439
>200ng/ml	1.683 (0.165–17.126)	0.660
CA125 (ng/ml) (>40ng/ml)	0.238 (0.040–1.410)	0.114
CA199 (ng/ml) (>40ng/ml)	0.913 (0.338–2.470)	0.858
Complications (yes)	1.176 (0.314–4.409)	0.809

Table 4 shows the results of univariate and multivariate analyses of factors affecting OS in patients with RCLM. Percentage circumference of intestinal wall involved (p<0.001), lymph node metastasis (p = 0.049) and the CA199 (p = 0.003) were the independent risk factor for OS in patients with RCLM.

Table 4

Univariate and multivariate analyses of factors affecting Overall survival in patients of RCLM
Variable	Univariate		Multivariate
	HR (95% CI)	P value	HR (95% CI)	P value
Sex (Male)	1.062 (0.272–4.153)	0.931
Age (≥ 60)	3.000 (0.786–11.445)	0.108
BMI (nomal)	2.161 (0.538–8.678)	0.277
Longitudinal diameter of primary tumor (≥ 5cm)	0.941 (0.241–3.679)	0.931
Percentage circumference of intestinal wall involved(=1)	0.099 (0.017–0.581)	0.010	8.034 (6.826–9.456)	<0.001
Number of liver metastases (>1)	0.646 (0.158–2.637)	0.543
Differentiation (Well)		0.999
pT0-pT3 stage	0.492 (0.134–1.810)	0.286
Lymph node metastasis (yes)	0.259 (0.067–1.003)	0.050	0.153 (0.024–0.995)	0.049
CEA (ng/ml)
>5ng/ml	1.547 (0.379–6.310)	0.543
>200ng/ml	6.000 (0.563–63.984)	0.138
CA125 (ng/ml) (>40ng/ml)	0.615 (0.104–3.658)	0.593
CA199 (ng/ml) (>40ng/ml)	0.196 (0.036–1.056)	0.058		0.003
Complications (yes)	0.472 (0.081–2.752)	0.404

Table 5 shows the results of univariate and multivariate analyses of factors affecting OS in patients with ReCLM. None of the factors were proved to be related to OS in patients with ReCLM.

Table 5

Univariate and multivariate analyses of factors affecting Overall survival in patients of ReCLM
Variable	Univariate		Multivariate
	HR (95% CI)	P value	HR (95% CI)	P value
Sex (Male)	0.750 (0.136–4.127)	0.741
Age (≥ 60)	1.145 (0.270–4.867)	0.854
BMI (nomal)	0.169 (0.018–1.592)	0.120
Longitudinal diameter of primary tumor (≥ 5cm)	0.538 (0.125–2.313)	0.405
Intestinal canal seepage(=1)	1.167 (0.251–5.413)	0.844
Number of liver metastases (>1)	0.857 (0.185–3.977)	0.844
Differentiation (Well)		0.999
pT0-pT3 stage	1.000 (0.192–5.222)	1.000
Lymph node metastasis (yes)	0.500 (0.103–2.436)	0.391
CEA (ng/ml)
>5ng/ml	0.407 (0.084–1.970)	0.264
>200ng/ml		0.162
CA125 (ng/ml) (>40ng/ml)		0.999
CA199 (ng/ml) (>40ng/ml)	0.350 (0.072–1.711)	0.195
Complications (yes)	0.500 (0.095–2.620)	0.412

Table 6 shows the results of univariate and multivariate analyses of factors affecting DFS in patients with CRLM. The Percentage circumference of intestinal wall involved (p<0.001) and CA199 (p = 0.084) were the independent risk factor for DFS in patients with CRLM.

Table 6

Univariate and multivariate analyses of factors affecting disease-free survival in patients
Variable	Univariate		Multivariate
	HR (95% CI)	P value	HR (95% CI)	P value
Sex (Male)	1.080 (0.545–2.140)	0.825
Age (≥ 60)	1.077 (0.543–2.135)	0.832
BMI (nomal)	0.980 (0.475–2.022)	0.956
Longitudinal diameter of primary tumor (≥ 5cm)	0.703 (0.352–1.406)	0.319
Percentage circumference of intestinal wall involved(=1)	0.252 (0.117–0.542)	<0.001	0.252 (0.116–0.547)	<0.001
Number of liver metastases (>1)	0.961 (0.458–2.018)	0.596
Differentiation (Well)	1.857 (0.188–18.329)	0.596
pT0-pT3 stage	0.665 (0.323–1.372)	0.270
Lymph node metastasis (yes)	0.601 (0.294–1.226)	0.161
CEA (ng/ml)
>5ng/ml	0.903 (0.432–1.886)	0.785
>200ng/ml	1.694 (0.405–7.079)	0.470
CA125 (ng/ml) (>40ng/ml)	0.375 (0.101–1.396)	0.114
CA199 (ng/ml) (>40ng/ml)	0.532 (0.258–1.096)	0.087	0.506 (0.233–1.097)	0.084
Complications (yes)	0.492 (0.192–1.261)	0.140

CRC is the one of the most common tumors in the world, and once liver metastases are confirmed, they will be defined as advanced tumors. Previously, metastatic colorectal cancer (mCRC) has been considered as one of the surgical contraindications, but in recent years, resection of liver metastases has been widely accepted with a prognostic benefit.

This study analyzed short- and long-term outcomes of CRLM to investigate the prognostic impact of primary tumor sites by classifying tumors into three groups: RCLM, LCLM, and ReCLM. The results showed that three-year OS of LCLM group and ReCLM group outstrips that of RCLM (RCLM: 37.5% vs. LCLM: 64.7% vs. ReCLM: 62.5%, p = 0.016). These results were partly consistent with some studies, which reported that the survival of RCLM patients was significantly lower than that of the LCLM and ReCLM patients (11–12, 14–17). However, due to the small sample size, there was no significant difference in five-year OS (RCLM: 37.5% vs. LCLM: 64.7% vs. ReCLM: 62.5%, p = 0.461). To sum up, different tumor locations of CRLM have different prognostic implications for survival after curative resection, which suggests that the primary tumor location might serve as a prognostic indicator in CRLM. This study proposes that RCLM, LCLM and ReCLM should be considered different solid tumors and elaborates implications of the distinction for clinical practice.

The theory of embryonic origin may explain why the location of the primary tumor may be a predictor of survival. The right-sided colon is derived from the embryonic mid-gut while the left-sided colon and rectum are derived from the embryonic hind-gut, which leads to differences in genetic background, tumor microenvironment, clinical manifestations, histological types, molecular characteristics, and blood supply (4–5). Therefore, if the primary tumor is located in the left colon, then the right colon and rectum tumors should be considered as three distinct solid tumors with different prognoses.

For most RCC, by the time it is discovered, it is usually very advanced because of the late onset of its clinical symptoms. On the contrary, the clinical symptoms of LCC and REC can be detected very early and can therefore be treated early as well, as long as the patient seeks medical attention. Those factors reported in this article are consistent with previous reports (18–20), including the ratio of longitudinal diameter of primary tumor ≥ 5cm (p = 0.001) and the ratio of Percentage circumference of intestinal wall involved=1(p = 0.021), which are all greater in the RCLM group than the LCLM and ReCLM groups.

Univariate analysis showed that the Percentage circumference of intestinal wall involved was the risk factor for OS of LCLM; the longitudinal diameter of primary tumor ≥ 5cm, Percentage circumference of intestinal wall involved and CA199 were the risk factors for OS of RCLM; and no risk factors were found for OS of ReCLM; multivariate analysis showed that Percentage circumference of intestinal wall involved and CA199 were independent risk factors for OS of RCLM and no independent risk factors were discovered for OS of LCLM and ReCLM. In addition, univariate analysis and multivariate analysis shown that the Percentage circumference of intestinal wall involved and CA199 not only were the risk factors for DFS of CRLM, but also were the independent risk factors for DFS of CRLM. Several studies had reported similar results as well (21–25). This may be because the larger the tumor, the greater the strain it puts on the body, and so more microinvasive and micro-metastases will go undetected. The tumor is infiltrating and growing around the bowel, which can lead to microinvasion and tumor residual and a worse prognosis. About the influence of tumor markers on prognosis, some studies had also found similar results (26–35). Carcinoembryonic antigen (CEA) is the most routinely used tumor for CRC, and it has been recommended by a large number of scholars for prognosis, detection of treatment response and detection of metastatic disease and recurrence; on the other hand, carbohydrate antigen 125 (CA125) is a sensitive tumor marker of peritoneal dissemination (PD), which has been linked to a lot of studies on colorectal cancer; carbohydrate antigen 199 (CA199) is a mucin-type carbohydrate protein tumor marker and a lot of studies have been related it to colorectal cancer (36–39). Thus, the longitudinal diameter of primary tumor, Percentage circumference of intestinal wall involved and CA199 readings may be the factors that we should prioritize since they help us develop individualized and systematic treatment for patients with CRLM.

Furthermore, according to the consensus reached in 2005, resectable was defined as: no uncurable extrahepatic lesions, suitable for surgery, and 30% of normal liver parenchyma can be retained after surgery, or the affected range is no more than 6 hepatic segments (40). Chemotherapy further provides the possibility of radical resection for patients with colorectal cancer liver metastases (41). Similar to our center, before surgical resection, most surgeons will require imaging proof of the absence of hepatic artery, major bile duct, portal vein trunk, or abdominal/para-aortic lymph node involvement, and adequate prediction of functional residual liver volume (42). Therefore, the removal of liver tissue does not accelerate the death of patients with colorectal cancer liver metastases.

Postoperative complications are one of the most important factors affecting the results of liver metastasis surgery for colorectal cancer (43–46). Complications can affect the recovery of patients or even delay the treatment of the primary disease due to the need for treatment of said complications. In our study, the major complications included intra-abdominal infection, followed by stomal fistula, pulmonary infection, incision infection, bile fistula, intestinal obstruction and others.

Tumor recurrence and metastasis in one of the most important factors affecting the long-term survival of patients with colorectal cancer liver metastasis (31, 47–50). The liver is most common site of colorectal cancer not only before surgery, but also after surgery. Our study showed that postoperative recurrence or metastasis was most common in liver, followed by pulmonary metastasis, relapse, liver and lung metastasis, brain metastasis, bone metastasis, adrenal metastasis and so on.

The study has some limitations. First, the small number of CRLM cases available in this study is irrefutable; second, we are lacking in powerful and definitive RCT results; third, data were obtained from a single-center; fourth, the surgery was performed by different treatment groups that may have different surgical techniques; fifth, the surgical learning curve was not considered; sixth, MDT diagnosis and treatment model has been implemented disproportionately more for recent cases than the past; seventh, due to the small number of neoadjuvant chemotherapy cases, neoadjuvant chemotherapy factors cannot be measured; eighth, study range is 2008–2021 a lot has changed in this period of time; finally, molecular detection and targeted immunotherapy are required to round up this study.

In this single-center retrospective study, the ratio of longitudinal diameter of primary tumor ≥ 5cm and Percentage circumference of intestinal wall involved for RCLM group are more than LCLM and ReCLM groups. the top three complications are intra-abdominal infection, stomal fistula and pulmonary infection, while the top three for recurrence or metastasis are liver metastases, pulmonary metastases and relapse. The prognosis of RCLM group was found to be worse than the LCLM and ReCLM group. We should consider the site of primary tumor as a stratification factor when we study the prognosis of CRLM.

Conflict of interest

The authors declare no conflict of interest.

Acknowledgements: We thank the First Affiliated Hospital, Sun Yat-sen University for providing us with a large amount of patient data.

Ethical Approval: not applicable.

Competing interests: The authors have no conflict of interest related to the Manuscript.

Authors’ contributions: Hui-Long Guo, Jing-Yao Chen, You-Zhen Tang and Wen-Hui Wu contributed equally to this study, and both conceptualized and designed the study, analyzed and interpreted the data, drafted the manuscript, and critically revised the manuscript for important intellectual content; Qian-Lin Zeng, Zhen Hu, Yi-Fan Zhang, Song Xiang and Ming-Zhe Li participated in data acquisition and statistical analysis; Yu-Long He supervised the whole study and monitored the standard surgical operations; all the authors took part in the surgical treatment of colorectal cancer.

Fundings: Guangdong Provincial Key Laboratory of Digestive Cancer Research (No. 2021B1212040006), Sanming Project of Medicine in Shenzhen (No. SZSM201911010), Shenzhen Key Medical Discipline Construction Fund (No. SZXK016), Guangdong–Hong Kong–Macau University Joint Laboratory of Digestive Cancer Research (2021LSYS003) and Shenzhen Fundamental Research Program (JCYJ20190809142807444).

Availability of date and materials: The original anonymous dataset is available on request from the corresponding author at [email protected].

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No competing interests reported.

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Prognostic impact of primary tumor site on liver metastasis in resectable colorectal cancer

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