Table 1.

Summary of prognostic and predictive biomarkers in stage II and III CC

Variable	Study	Sample size	Disease stage and characteristics	1° Endpoint	HR	CI 95%	p value	Type of analysis	Ref
MSI vs MSS	PETACC-3	1404	II and III	OS	0.49	0.34–0.69	0.001	univariate	[16]
				RFS	0.47	0.31–0.72	<0.001	univariate
	QUASAR	1913	II and III	RFS	0.53	0.40–0.70	<0.001	univariate	[17]
	ACCENT	2723	III treated	OS	0.79	0.65–0.97	0.023	univariate	[18]
				TTR	0.80	0.66–0.97	0.025	univariate
		307	II untreated	TTR	0.27	0.10–0.75	0.012	univariate
				OS	0.27	0.10–0.74	0.011	univariate
	NSABP	1796	II and III	OS	0.64	0.46–0.89	0.008	multivariate	[19]
	C-07/C-08
				TTR	0.48	0.33–0.70	0.0001	multivariate
	NO147	2580	III	DFS	0.82	0.64–1.07	0.1403	multivariate	[20]
			III left	DFS	1.71	0.99–2.95	0.0564	multivariate
			III right	DFS	0.71	0.53–0.94	0.0184	multivariate
	CALGB89803	891	III left	DFS	1.58	0.72–3.46	0.2817	multivariate
			III right	DFS	0.59	0.41–0.86	0.0039	multivariate
BRAF MUT vs WT	PETACC-3	1423	II and III	OS	1.78	1.26–2.53	0.0009	univariate	[21]
				RFS	1.30	0.94–1.81	0.1174	univariate
				SAR	2.48	1.74–3.53	<0.0001	univariate
		697	II and III, MSS/left	OS	6.41	3.57–11.52	<0.0001	univariate
				RFS	3.57	2.02–6.31	0.0005	univariate
		1054	II and III, MSS	OS	2.82	1.58–4.30	<0.0001	univariate
	QUASAR	1584	II and III	RR	0.84	0.57–1.23	0.4	univariate	[17]
	NSABP	2226	II and III	OS	1.46	1.20–1.79	0.0002	univariate	[19]
	C-07/C-08
				TTR	1.02	0.82–1.28	0.86	univariate
				SAR	2.31	1.83–2.95	<0.0001	univariate
		201	II and III, MSI	OS	1.76	0.88–3.49	0.11	multivariate
		1534	II and III, MSS	OS	1.58	1.23–2.04	0.0004	multivariate
	CALGB89803	506	III	OS	1.66	1.05–2.63	0.015	univariate	[22]
		428	III, MSS	OS	1.61	0.96–2.69	NA	multivariate
	NO147	2515	III	DFS	1.34	1.11–1.63	0.0028	univariate	[20]
		2176	III, MSS	DFS	1.32	1.01–1.73	0.0437	multivariate
		304	III, MSI	DFS	1.58	0.88–2.82	0.1220	multivariate
	Meta-analysis of 7 RCT	8721	II and III	OS	1.42	1.25–1.60	<0.0001	univariate	[23]
				DFS	1.26	1.07–1.48	0.006	univariate
KRAS MUT vs WT	PETACC-3	1423	II and III	OS	1.09	0.86–1.37	0.4826	univariate	[21]
				RFS	1.04	0.85–1.27	0.7245	univariate
				SAR	1.04	0.82–1.32	0.7222	univariate
	NSABP	2081	II and III	OS	1.09	0.92–1.29	0.33	univariate	[19]
	C-07/C-08
				TTR	1.12	0.94–1.32	0.21	univariate
				SAR	1.11	0.92–1.34	0.30	univariate
	QUASAR	1583	II and III	RR	1.40	1.12–1.74	0.002	univariate	[17]
	Prospective cohort	1075	I-IV BRAF WT, KRAS codon 12 mut vs wt	CCSM	1.30	1.02–1.67	0.037	multivariate	[24]
				OS	1.24	1.02–1.51	0.029	multivariate
			I-IV BRAF WT, KRAS codon 13 mut vs wt	CCSM	0.86	0.58–1.27	NS	multivariate
				OS	0.96	0.71–1.30	NS	multivariate
	NO147	2478	III BRAF WT, KRAS codon 12 mut vs wt	DFS	1.52	1.28–1.80	<0.0001	multivariate	[25]
			III BRAF WT, KRAS codon 13 mut vs wt	DFS	1.36	1.0–1.77	0.0248	multivariate
	PETACC-8	1629	III	TTR	1.56	1.2–1.92	<0.001	multivariate	[26]
		1043	III BRAF WT, left, KRAS codon 12 mut vs wt	TTR	1.96	1.5–2.56	<0.0001	multivariate
			III BRAF WT, left, KRAS codon 13 mut v wt	TTR	1.59	1.0–2.56	0.051	multivariate
ERBB2 alterations vs WT	PETACC-8	1800	III	TTR	1.55	1.02–2.36	0.04	univariate	[27]
				OS	1.57	0.99–2.5	0.05	univariate
CDX2 neg vs pos	Independent and retrospective cohorts	466	II and III	DFS	2.73	1.58–4.72	<0.001	multivariate	[15]
		314	II and III	DFS	2.42	1.36–4.29	0.003	multivariate
SMAD4 loss vs no loss	PETACC-3	1381	II and III	OS	1.58	1.23–2.01	<0.001	multivariate	[28]
				RFS	1.47	1.19–1.81	<0.001	multivariate
Low IM vs High IM	Prospective cohort	690	I, II and III	TTR	0.35	0.23–0.52	<0.0001	univariate	[29]
		630	I, II and III	TTR	0.54	0.34–0.84	0.006	univariate

MSI: Microsatellite Instability, MSS: Microsatellite Stable, OS: Overall Survival, RFS: Relapse Free Survival, TTR: Time To Relapse, HR: Hazard Ratio, CI: Confidence Interval, mut: mutation, WT: Wild Type, SAR: Survival After Recurrence, DFS: Disease Free Survival, RR: Response Rate, CCSM: Colorectal Cancer-Specific Mortality, and IM: Immunoscore