Table 2.

Final multivariable overall survival Cox models across clinical trial cohorts and different observational studies

Cohorts with adjuvant chemotherapy exposure	Train (n=3016; 550 events)				Val1 (n=1499; 307 events)				Val2 (n = 949; 151 events)
	HR	95% CI		P value	HR	95% CI		P value	HR	95% CI		P value
pT3 versus pT2/pT1	2.43	1.59	3.73	<0.001	1.67	1.05	2.66	<0.001	1.45	0.66	3.17	0.35
pT4 versus pT2/pT1	4.83	3.08	7.59	<0.001	2.81	1.69	4.66	<0.001	3.39	1.47	7.84	0.004
pN1 versus pN0	1.79	1.20	2.66	0.004	NA	NA	NA	NA	2.69	1.66	4.37	<0.001
pN2 versus pN0a	3.09	2.04	4.68	<0.001	1.47	1.09	1.98	0.01	3.27	1.86	5.72	<0.001
Age in years (continuous)	1.01	1.00	1.02	0.01	1.01	1.00	1.02	0.02	1.01	1.00	1.03	0.07
Male versus female	1.36	1.15	1.62	<0.001	1.48	1.17	1.88	0.001	1.28	0.92	1.78	0.14
LN assessed ≥12 versus <12	0.74	0.60	0.91	0.004	0.63	0.48	0.83	<0.001	1.17	0.84	1.62	0.35
LN positive (continuous)	1.06	1.04	1.08	<0.001	1.11	1.07	1.14	<0.001	1.08	1.04	1.12	<0.001
High grade versus low/medium	1.35	1.11	1.64	0.003	1.35	1.11	1.64	0.003	1.38	0.93	2.05	0.11
Right colon versus left colon	1.46	1.21	1.77	<0.001	1.65	1.28	2.12	<0.001	1.31	0.92	1.85	0.13
FOLFIRIb versus 5FU/LV	1.15	0.81	1.62	0.44	0.86	0.61	1.20	0.37	NA	NA	NA	NA
FOLFIRIb/cetuximab versus 5FU/LV	0.54	0.19	1.50	0.24	0.36	0.05	2.62	0.31	NA	NA	NA	NA
FOLFOXc versus 5FU/LV	0.76	0.55	1.05	0.09	0.65	0.47	0.90	0.01	0.77	0.47	1.26	0.3
FOLFOXc/cetuximab versus 5FU/LV	0.97	0.70	1.35	0.88	0.83	0.59	1.17	0.29	NA	NA	NA	NA
MSI-high versus MSS/MSI-low	0.75	0.57	0.99	0.043	0.72	0.49	1.05	0.08	0.44	0.25	0.77	0.004
BRAF V600E mutation versus wt	1.63	1.25	2.12	<0.001	2.53	1.78	3.60	<0.001	1.94	1.19	3.16	0.007
KRAS codons 12/13 mutation versus Wt	1.49	1.24	1.81	<0.001	1.42	1.10	1.84	0.007	1.35	0.95	1.93	0.09
Cohorts without adjuvant chemotherapy exposure	Val3 (n=1080; 286 events)				Val4 (n=782; 179 events)
	HR	95% CI		P value	HR	95% CI		P value
pT3 versus pT2/pT1	1.77	0.65	4.83	0.26	4.46	1.64	12.15	0.004
pT4 versus pT2/pT1	3.29	1.16	9.35	0.02	11.18	3.64	34.39	<0.001
pN1 versus pN0	1.45	1.04	2.01	0.03	1.82	1.31	2.53	<0.001
pN2 versus pN0	1.72	1.11	2.64	0.01	1.53	0.86	2.74	0.14
Age in years (continuous)	1.05	1.04	1.07	<0.001	NA	NA	NA	NA
Male versus female	1.08	0.85	1.38	0.52	NA	NA	NA	NA
LN assessed ≥12 versus <12	1.22	0.97	1.55	0.09	NA	NA	NA	NA
LN positive (continuous)	1.04	1.00	1.07	0.03	NA	NA	NA	NA
High grade versus low/medium	0.99	0.63	1.55	0.97	NA	NA	NA	NA
Right colon versus left colon	0.70	0.54	0.91	0.007	NA	NA	NA	NA
MSI-high versus MSS/MSI-low	0.49	0.32	0.77	0.002	0.97	0.64	1.47	0.88
BRAF V600E mutation versus wt	1.64	1.03	2.62	0.04	1.72	1.10	2.69	0.02
KRAS codons 12/13 mutation versus wt	1.13	0.87	1.48	0.36	1.28	0.92	1.78	0.13

^aIn Val2, pN2 versus pN1.

^bInfusional 5FU with irinotecan.

^cInfusional 5FU with oxaliplatin.