Surgery for colorectal liver metastases: The evolution of determining prognosis

Table 1 Studies of prognostic clinicopathological factors

Study	Primary stage	CEA level	Size of major metastasis	Number liver metastases	Disease free interval	Extrahepatic disease	Surgical margins
Scheele et al[11]	P	NA	P	NP	P	P	P
Nordlinger et al[10]	P	P	P	P	P	NA	P
Fong et al[9]	P	P	P	P	P	P	P
Mann et al[12]	P	P	P	NP	NP	NA	NA
Rees et al[15]	P	P	P	P	NA	P	P
John et al[21]	NP	P	NP	NP	NA	NP	P
Doci et al[27]	P	NP	NP	NP	NP	NA	NA
Hughes et al[34]	P	P	P	P	P	NA	NA
Gayowski et al[37]	P	NA	NP	P	NP	P	P

CEA: Carcinoembryonic antigen; P: Prognostic; NP: Non prognostic; NA: Non available.

Table 2 Survival based on the clinical risk cumulative score (adapted from Fong et al[9])

Cumulative score	1 yr	2 yr	3 yr	4 yr	5 yr	Median, mo
0	93	79	72	60	60	74
1	91	76	66	54	44	51
2	89	73	60	51	40	47
3	86	67	42	25	20	33
4	70	45	38	29	25	20
5	71	45	27	14	14	22
Prognostic factor	Score 0	Score 0	Score 0	Score 1	Score 1	Score 1
Node-positive primary	negative	negative	negative	positive	positive	positive
Disease-free interval	≥ 12 mo	≥ 12 mo	≥ 12 mo	< 12 mo	< 12 mo	< 12 mo
Number of liver metastases	1	1	1	> 1	> 1	> 1
Size of major liver metastases	≤ 5 cm	≤ 5 cm	≤ 5 cm	> 5 cm	> 5 cm	> 5 cm
CEA (ng/mL)	< 200 ng/mL	< 200 ng/mL	< 200 ng/mL	> 200 ng/mL	> 200 ng/mL	> 200 ng/mL

CEA: Carcinoembryonic antigen.

Table 3 Studies of prognostic biomarkers

Study	No. of patients	Positive case (%)	Biomarker	Correlation with survival
Nash et al[110]	188	27	KRAS	Independent predictor of poor survival (HR = 1.9)
Nash et al[110]	188	62	Ki-67	Independent predictors of poor survival (HR = 2.6)
Teng et al[113]	292	2.1	BRAF	Independent prognostic biomarker after metastasectomy (HR = 6.245, P < 0.003)
Smith et al[26]	66	36	Ki-67	Ki-67 correlate with survival (P = 0.04)
Smith et al[26]	66	35	hTERT	Htert correlate with survival (P = 0.0001)
Dômont et al[25]	201	43	hTERT	Independent predictor of poor survival
				(RR = 2.03, P < 0.0001)
Gonen et al[123]	156	Not reported	TS	Independent predictor of poor survival
				(RR = 4.22, P < 0.01)
Costa et al[137]	104	Not reported	TLI	High TLI independently
				Predicted decreased DFS
				(P = 0.035)
Nitti et al[128]	69	64	p53	Independent predictor of poor survival
				(RR = 2.53, P = 0.008)
Mehta et al[144]	50	30	FGA	A high FGA is an independent predictor of survival (P = 0.01)
Shimomura et al[136]	64	31	HIF-1α	High HIF-1α is an independent risk factor for recurrence

hTERT: Human telomerase reverse transcriptase; TS: Thymidylate synthase; TLI: Thymidylate labeling index; DFS: Disease free survival; FGA: Fraction of genome altered; HIF-1α: Hypoxia inducible factor-1α.