Table 2.

Multivariable Cox proportional hazards model analysis for OS and RFS in 490 patients^*

Factor	No. of patients	No. of events	Multivariable HR†	95% CI	P value
OS
Gene mutation
BRAF	10	6	2.95	1.27–6.86	0.012
RAS	249	87	2.14	1.53–2.99	< 0.001
TP53	347	123	2.21	1.49–3.28	< 0.001
SMAD4	55	25	1.82	1.17–2.83	0.008
Clinicopathologic factors
Largest liver metastasis diameter	–	–	1.07	1.01–1.13	0.033
Surgical margin, positive	97	33	1.83	1.23–2.72	0.003
	RFS
Gene mutation
RAS	249	206	1.47	1.20–1.82	< 0.001
TP53	347	283	1.40	1.11–1.78	0.005
SMAD4	55	51	1.62	1.20–2.20	0.002
Patients factors
Age			1.01	1.00–1.02	0.024
Clinicopathologic factors
Number of CLM	–	–	1.04	1.01–1.07	0.006
Largest liver metastasis diameter	–	–	1.08	1.04–1.13	< 0.001
Prehepatectomy chemotherapy‡	134	117	1.45	1.16–1.82	0.001
Extrahepatic disease	79	74	1.70	1.31–2.21	< 0.001
Surgical margin, positive	97	80	1.43	1.11–1.85	0.006

Abbreviations: HR, hazard ratio; CI, confidence interval, CLM, colorectal liver metastasis.

^*Of the 507 patients, 490 patients were analysed because data were unavailable for T category in 8 patients and lymph node metastasis in 14 patients.

^†The Cox proportional hazards model analysis initially included age (continuous variable), sex, primary tumor location, T category, primary lymph node metastasis, prehepatectomy carcinoembryonic antigen level (continuous variable), timing of metastasis (synchronous vs. metachronous), prehepatectomy chemotherapy, extrahepatic disease, number of CLM (continuous variable), largest liver metastasis diameter (continuous variable), surgical margin status (R1 vs. R0), BRAF mutation, RAS mutation, TP53 mutation, APC mutation, PIK3CA mutation, and SMAD4 mutation. A backward elimination with a threshold P value of 0.05 was used to select variables for the final models.

^‡> 6 cycles vs. ≤ 6 cycles or no prehepatectomy chemotherapy.