Is precision medicine for colorectal liver metastases still a utopia? New perspectives by modern biomarkers, radiomics, and artificial intelligence

Table 1 Characteristics of different biomarkers of colorectal liver metastases.

	Biomarker characteristics
	Standardized	Reproducibility	Robustness (across series)	Early assessment	Reliability in prediction	(Potential) Clinical impact
Morphology and clinical data	d	e	c	e	b	c
Dynamic evaluation	d	e	e	b	d	e
Genetics	c	d	d	e	e	e
Peritumoral tissue data	c	d	c	a	d	d
Radiomics	b	c	c	e	c	d
Artificial intelligence	a	a	b	d	d	e

The performances of every biomarker are evaluated by a score, ranging from “a” if very low to “e” if very high.

Table 2 Some of the available scores for outcome prediction of patients with colorectal liver metastases candidates to surgery

	Morphology-based scores				Morphology- and Genetics-based scores
	Nordlinger et al[18], 1996	CRS, Fong et al[19], 1999	Iwatsuki et al[20], 1999	Rees et al[21], 2008	RAS Mutation CRS, Brudvik et al[60] 2017	GAME score, Margonis et al[61] 2018	Extended CRS, Lang et al[65], 2019
Morphological parameters
Age	Yes (60 yr)
Primary tumor
Extension into the serosa	Yes
N status primary tumor	Yes	Yes		Yes	Yes	Yes	Yes
Grading primary tumor				Yes
Liver metastases
Number	Yes (3)	Yes (1)	Yes (2)	Yes (3)		Yes (TBS)
Size	Yes (50 mm)	Yes (50 mm)	Yes (80 mm)	Yes (50 mm)	Yes (50 mm)		Yes (50 mm)
Bilobar			Y
DFI	Yes (24 mo)	Yes (12 mo)	Yes (30 mo)
Surgical margin	Yes (10 mm)
Extrahepatic disease				Yes		Yes
CEA value		Yes (200 ng/mL)		Yes (60 ng/mL)		Yes (20 ng/mL)
Genetic parameters
RAS					Yes	Yes1
RAS/RAF pathway							Yes
SMAD							Yes

¹KRAS status.

DFI: Disease-free interval from primary to metastases; CEA: Carcinoembryonic antigen; CRS: Clinical risk score; GAME: Genetic and morphological evaluation; TBS: Tumor Burden Score.