Prognostic role of serum carcinoembryonic antigen in patients receiving liver resection for colorectal cancer liver metastasis: A meta-analysis

Table 1 Basic features of the included literature

No.	Ref.	Country	Study type	Treatment	Univariate/multivariate analysis	Cut-off (ng/mL)	Sample size	Age	Male/female	Outcomes	Nos
1	Meng et al[34], 2021	China	Cohort study	Hepatectomy + chemotherapy	Multivariate	100	234	Range (n): < 65, 164; ≥ 65, 70	126/108	OS	9
2	Okimoto et al[35], 2017	Japan	Cohort study	Hepatectomy + chemotherapy	Multivariate	10	134	Median (range): 63 (30-87)	90/44	OS	8
3	Kamphues et al[53], 2021	Germany	Cohort Study	Hepatectomy	Multivariate	6.15	1643	Median (range): 62 (18-90)	1018/625	OS	7
4	Kawahara et al[36], 2018	Japan	Cohort study	Hepatectomy	Univariate	5/50	66	Median (range): 65.2 (31-80)	45/21	RFS	7
5	Hof et al[54], 2016	The Netherlands	Cohort study	Hepatectomy	Multivariate	200	431	mean ± SD: 62.9 ± 9.4	264/167	OS	8
6	Chiang et al[37], 2019	China	Cohort study	Hepatectomy + chemotherapy	Multivariate	5	490	Median (range): 60.3 (28.8-88.0)	332/158	RFS, OS	8
7	Peltonen et al[55], 2018	Finland	Cohort study	Hepatectomy + chemotherapy	Univariate	5	168	Median (range): 64.3 (36.3-81.5)	101/67	OS, DFS	8
8	Lu et al[38], 2016	China	Cohort study	Hepatectomy + chemotherapy	Univariate	5	141	Median (range): 60 (20-82)	92/49	OS	7
9	John et al[56], 2013	United Kingdom	Cohort study	Hepatectomy + chemotherapy	Univariate	200	432	Median (range): 64.5 (29-85)	289/143	OS	7
10	Yi et al[39], 2013	Korea	Cohort study	Hepatectomy + chemotherapy	Multivariate	5	76	Median (range): 57(31-75)	47/29	DFS	8
11	Gervaz et al[57], 2000	Switzerland	Cohort study	Hepatectomy	Univariate	4	49	≥ 18	35/14	OS	7
12	Sasaki et al[40], 2005	Japan	Cohort study	Hepatectomy	Multivariate	10	103	Range (n): ≤ 32, 164; > 60, 71	56/47	OS	9
13	Wang et al[41], 2017	China	Cohort study	Hepatectomy + chemotherapy	Multivariate	5	159	Median (range): Non-targeted therapy group 52 (35-83); bevacizumab combined treatment group 43 (32-71); cetuximab combined treatment group 59 (28-76)	101/58	RFS, OS	8
14	Takamizawa et al[42], 2022	Japan	Cohort study	Hepatectomy	Multivariate	5	554	Median (range): 62 (21-88)	358/196	RFS, OS	9
15	Masuda et al[64], 2018	United States	Cohort study	Hepatectomy + RFA	Multivariate	30	116	mean ± SD: tumors ≥ 4, 58.7 ± 10.6; tumors < 4, 57.6 ± 12.0	74/42	OS	7
16	Zhang et al[43], 2017	China	Cohort study	Hepatectomy	Multivariate	100	102	Range (n): < 60, 66; ≥ 60, 36	63/39	OS	9
17	Ishii et al[44], 2022	Japan	Cohort study	Hepatectomy	Univariate	5	90	Median (range): High CII 65 (31-87); low CII 65 (32-82)	58/32	RFS, OS	7
18	Tanaka et al[45], 2008	Japan	Cohort study	Hepatectomy + chemotherapy	Multivariate	12	79	Range (n): ≥ 60, 46; < 60, 33	49/30	OS	9
19	Sasaki et al[65], 2016	United States	Cohort study	Hepatectomy + RFA	Multivariate	30	485	Median (IQR): 58.5 (49.1-66.5)	290/195	OS	8
20	Chen et al[46], 2020	China	Cohort study	Hepatectomy + chemotherapy	Univariate	10	141	Median (IQR): 55 (49.0-62.0)	92/49	PFS, OS	7
21	Montalti et al[58], 2015	Belgium	Cohort study	Hepatectomy + chemotherapy	Multivariate	10	114	mean ± SD: 66.4 ± 0.89	78/36	OS, RFS	6
22	Reddy et al[67], 2009	United States	Cohort study	Hepatectomy + chemotherapy	Multivariate	200	499	Median (range): 57(49-66)	294/205	OS	6
23	Reddy et al[66], 2009	United States	Cohort study	Hepatectomy + chemotherapy	Multivariate	10	230	Median (range): 61(33-83)	137/93	OS	7
24	Li et al[47], 2023	China	Cohort study	Hepatectomy + chemotherapy	Univariate	200	431	Median (IQR): 59 (49-68)	282/149	RFS, OS	7
25	Niu et al[68], 2007	Australia	Cohort study	Hepatectomy	Multivariate	5	315	mean ± SD: 62 ± 11	239/176	OS	6
26	Polivka et al[59], 2020	The Czech Republic	Cohort study	Hepatectomy	Multivariate	4.9	71	Median (range): 62.7 (29-77)	29/42	DFS, OS	6
27	Takeda et al[48], 2022	Japan	Cohort study	Hepatectomy + chemotherapy	Multivariate	10	238	Range (n): < 60, 123; ≥ 60, 115	184/54	OS	8
28	Dumarco et al[69], 2023	Brazil	Cohort study	Hepatectomy	Multivariate	20	137	Median (range): 58.2 (23-87)	75/62	OS, DFS	8
29	Kim et al[49], 2019	Korea	Cohort study	Hepatectomy + chemotherapy	Multivariate	100	83	mean ± SD: 59.5 ± 10.0	62/21	OS	8
30	Peng et al[50], 2017	China	Cohort study	Hepatectomy	Univariate	200	150	Median (range): 58 (20-82)	97/53	RFS, OS	7
31	Imai et al[60], 2016	France	Cohort study	Hepatectomy	Multivariate	50	846	Median (range): 61 (28-89)	502/344	OS	8
32	Pawlik et al[61], 2005	Switzerland	Cohort study	Hepatectomy	Multivariate	200	566	Median 60	221/345	OS	6
33	Miki et al[51], 2018	Japan	Cohort study	Hepatectomy	Multivariate	5	73	Median (range): 59 (27-82)	49/24	DFS	8
34	Hohenberger et al[62], 1994	Germany	Cohort study	Hepatectomy	Univariate	5	166	Median (range): 59 (30-79)	99/67	OS	7
35	Arru et al[65], 2008	Italy	Cohort study	Hepatectomy	Multivariate	5/200	297	Range (n): < 65, 177; ≥ 65, 120	171/126	OS	8
36	Yoshino et al[52], 2022	Japan	Cohort study	Hepatectomy	Multivariate	5	633	Median (range): 64.0 (27.0-92.0)	414/219	RFS, OS	8

OS: Overall survival; DFS: Disease-free survival; RFS: Recurrence-free survival; IQR: Interquartile range; RFA: Radiofrequency ablation; PFS: Progression-free survival.

Table 2 Summary of meta-analysis results

Outcome	Number of studies	Model	Hazard ratio (95%CI)	P value	Heterogeneity (P value, I2)
Pre-LR
OS	28	Fixed	1.61 (1.49-1.75)	< 0.001	0.035, 34.9%
Region
Europe	8	Fixed	1.60 (1.41-1.82)	< 0.001	0.086, 42.3%
Asia	15	Fixed	1.43 (1.25-1.63)	< 0.001	0.377, 6.8%
South America	1	Fixed	1.31 (0.78-2.20)	0.307	/
North America	4	Fixed	2.21 (1.82-2.69)	< 0.001	0.980, 0.0%
Treatment modality
LR alone	12	Fixed	1.46 (1.31-1.64)	< 0.001	0.405, 4.1%
LR + chemotherapy	14	Fixed	1.74 (1.52-1.98)	< 0.001	0.053, 41.4%
LR + radiofrequency ablation	2	Fixed	2.18 (1.63-2.91)	< 0.001	0.844, 0.0%
Analysis modality
Multivariate	20	Fixed	1.70 (1.55-1.87)	< 0.001	0.099, 29.8%
Univariate	6	Fixed	1.23 (1.00-1.52)	0.053	0.618, 0.0%
Survival curve	2	Fixed	1.62 (1.24-2.13)	< 0.001	0.067, 70.2%
Cut-off
≤ 5 ng/mL	9	Fixed	0.32 (0.21-0.43)	< 0.001	0.570, 0.0%
5-50 ng/mL	11	Fixed	0.54 (0.42-0.66)	< 0.001	0.034, 48.7%
100 ng/mL	3	Fixed	0.60 (0.11-1.09)	0.017	0.407, 0.0%
200 ng/mL	6	Fixed	0.65 (0.45-0.84)	< 0.001	0.565, 0.0%
DFS	4	Random	1.49 (0.97-2.29)	0.067	0.109, 50.4%
Region
South America	1	Random	1.89 (1.13-3.15)	0.015	/
Asia	1	Random	1.27 (0.63-2.57)	0.507	/
Europe	2	Random	1.65 (0.55-4.93)	0.373	0.049, 74.2%
Treatment modality
LR alone	3	Random	1.81 (1.20-2.72)	0.005	0.340, 7.4%
LR + chemotherapy	1	Random	1.04 (0.71-1.53)	0.833	/
Analysis modality
Multivariate	3	Random	1.81 (1.20-2.72)	0.005	0.340, 7.4%
Univariate	1	Random	1.04 (0.71-1.53)	0.833	/
Cut-off
> 5 ng/mL	1	Random	1.89 (1.13-3.15)	0.015	/
≤ 5 ng/mL	3	Random	1.37 (0.80-2.35)	0.255	0.142, 48.7%
RFS	8	Fixed	1.27 (1.11-1.45)	< 0.001	0.117, 37.8%
Region
Asia	7	Fixed	1.25 (1.09-1.43)	0.001	0.101, 41.6%
Europe	1	Fixed	1.71 (0.90-3.24)	0.101	/
Treatment modality
LR alone	5	Fixed	1.32 (1.14-1.53)	< 0.001	0.176, 34.8%
LR + chemotherapy	3	Fixed	1.10 (0.83-1.47)	0.509	0.135, 50.1%
Analysis modality
Univariate	3	Fixed	1.07 (0.76-1.49)	0.709	0.569, 0.0%
Survival curve	1	Fixed	1.85 (0.99-3.47)	0.055	/
Multivariate	4	Fixed	1.29 (1.11-1.49)	0.001	0.030, 66.5%
Cut-off
≤ 5 ng/mL	5	Fixed	0.22 (0.08-0.37)	0.003	0.060, 55.7%
5-50 ng/mL	2	Fixed	0.62 (0.12-1.13)	0.016	0.669, 0.0%
200 ng/mL	2	Fixed	0.11 (-0.32 to 0.54)	0.615	0.313, 1.9%
Post-LR
OS	8	Random	2.66 (2.10-3.38)	< 0.001	0.002, 68.7%
Region
Asia	2	Random	2.63 (1.87-3.70)	< 0.001	0.040, 76.2%
Europe	5	Random	3.04 (2.10-4.40)	< 0.001	0.022, 65.1%
Oceania	1	Random	1.63 (1.09-2.42)	0.016	/
Treatment modality
LR + chemotherapy	2	Random	2.75 (1.70-4.44)	< 0.001	0.046, 74.8%
LR alone	6	Random	2.66 (1.91-3.69)	< 0.001	0.003, 71.9%
Analysis modality
Multivariate	5	Random	2.23 (1.79-2.78)	< 0.001	0.061, 55.7%
Survival curve	2	Random	4.40 (2.58-7.51)	< 0.001	0.215, 35.0%
Univariate	1	Random	3.68 (2.35-5.79)	< 0.001	/
Cut-off
≤ 5 ng/mL	6	Random	1.07 (0.78-1.37)	< 0.001	0.001, 74.9%
5-50 ng/mL	1	Random	0.74 (0.36-1.13)	< 0.001	/
200 ng/mL	1	Random	0.64 (0.10-1.17)	0.019	/
DFS	2	Fixed	3.23 (2.20-4.75)	< 0.001	0.182, 43.8%
RFS	2	Fixed	2.38 (2.05-2.77)	< 0.001	0.160, 49.3%

OS: Overall survival; DFS: Disease-free survival; RFS: Recurrence-free survival; CI: Confidence interval; LR: Liver resection.