Efficacy of neoadjuvant chemotherapy for initially resectable colorectal liver metastases: A retrospective cohort study

Table 1 Patient characteristics before propensity score matching

Variables		Upfront hepatectomy (n = 238)	NAC (n = 59)	P value
Patient-related
Age	< 60	123	14	< 0.001
	≥ 60	115	45
Gender	Male	184	39	0.07
	Female	54	20
CEA level (ng/mL)	< 10	73	19	0.82
	≥ 10	165	40
Primary tumor-related
Site	Right	34	15	0.03
	Left	204	44
Histology	Well/moderately differentiated	236	57	0.128
	Others	2	2
Lymph node metastases	0	144	17	< 0.001
	≥ 1	94	42
Depth of invasion	Adjacent organ invasion (T4b)	14	9	0.01
	Others	224	50
Lymphatic invasion	0	146	29	0.08
	≥ 1	92	30
Venous invasion	0	91	18	0.27
	≥ 1	147	41
Liver metastasis-related
Number	1–3	233	48	< 0.001
	≥ 4	5	11
Size (max)	< 40	180	18	0.06
	≥ 40	58	41
Timing of the appearance	Synchronous	40	37	< 0.001
	Metachronous	198	22
Distribution	Unilobar	211	38	< 0.001
	Bilobar	27	21
Treatment-related
Staged hepatectomy	Performed	0	1	0.04
	Not performed	238	58
Surgical margin	Exposed	13	6	0.186
	Not exposed	225	53
Adjuvant chemotherapy after primary resection	Administered	69	32	< 0.001
	Not administered	169	27
Adjuvant chemotherapy after hepatectomy	Administered	86	23	0.684
	Not administered	152	36

CEA: Carcinoembryonic antigen; NAC: Neoadjuvant chemotherapy.

Table 2 Prognostic factors for upfront hepatectomy

Variables		n	5-yr OS rate (%)	P value	Hazard ratio (95%CI)	P value
Patient-related
Age (yr)	< 60	60	65.7	0.24
	≥ 60	178	66.7
Sex	Male	167	66.5	0.28
	Female	71	65.8
CEA level (ng/mL)	< 10	122	75	0.01	1.948 (1.252–3.031)	0.003
	≥ 10	116	58.4
Primary tumor-related
Site	Left	190	56.2	0.14
	Right	48	68.5
Histology	Well/moderately differentiated	234	67.1	0.01	2.971 (1.038–8.503)	0.04
	Others	4	25
Lymph node metastases	0	108	79	0.001	1.623 (1.020–2.583)	0.04
	≥ 1	130	56.6
Depth of invasion	Adjacent organ invasion (T4b)	19	64.8	0.64
	Others	219	66.4
Lymphatic invasion	0	116	73.1	0.02	1.418 (0.897–2.242)	0.135
	≥ 1	122	60.8
Venous invasion	0	81	69.7	0.73
	≥ 1	157	63.9
Number	1–3	228	67.5	0.07
	≥ 4	10	38.1
Maximum diameter (mm)	< 40	180	70.9	0.05
	≥ 40	58	52.9
Timing of the appearance	Synchronous	54	61.2	0.94
	Metachronous	184	67.8
Distribution	Unilobar	198	67.1	0.12
	Bilobar	40	63
Treatment-related
Staged hepatectomy	Performed	0	–	–
	Not performed	238	66.3
Surgical margins	Exposed	19	40.1	0.09
	Not exposed	219	69
Adjuvant chemotherapy after primary resection	Administered	69	64.9	0.16
	Not administered	169	66.7
Adjuvant chemotherapy after hepatectomy	Administered	126	56.2	0.02	0.646 (0.414–1.009)	0.05
	Not administered	112	71.7

CEA: Carcinoembryonic antigen; CI: Confidence interval; OS: Overall survival.

Table 3 Patient characteristics after propensity score matching

Variables		Upfront hepatectomy group (n = 50)	NAC group (n = 50)	P value
Patient-related
Age (yr)	< 60	14	10	0.349
	≥ 60	36	40
Sex	Male	33	34	0.832
	Female	17	16
CEA level (ng/mL)	< 10	28	34	0.216
	≥ 10	22	16
Primary tumor-related
Site	Right	10	14	0.349
	Left	40	36
Histology	Well/moderately differentiated	49	50	0.315
	Others	1	0
Lymph node metastases	0	15	15	1.0
	≥ 1	35	35
Depth of invasion	Adjacent organ invasion (T4b)	5	3	0.461
	Others	45	47
Lymphatic invasion	0	19	23	0.418
	≥ 1	31	27
Venous invasion	0	16	15	0.829
	≥ 1	34	35
Liver metastasis-related
Number	1–3	44	42	0.564
	≥ 4	6	8
Maximum diameter (mm)	< 40	15	15	1.0
	≥ 40	35	35
Timing of the appearance	Synchronous	28	28	1.0
	Metachronous	22	22
Distribution	Unilobar	33	33	1.0
	Bilobar	17	17
Treatment-related
Staged hepatectomy	Performed	0	1	0.315
	Not performed	50	49
Surgical margins	Exposed	4	4	1.0
	Not exposed	46	46
Adjuvant chemotherapy after primary resection	Administered	17	29	0.144
	Not administered	23	21
Adjuvant chemotherapy after hepatectomy	Administered	23	17	0.221
	Not administered	27	33
Risk stratification	High-risk	18	13	0.515
	Low-risk	32	37

CEA: Carcinoembryonic antigen; NAC: Neoadjuvant chemotherapy.

Table 4 Recurrence patterns/treatment after propensity score matching

	Upfront hepatectomy group (n = 50)	NAC group (n = 50)	P value
Recurrence	30	24	0.229
Recurrence site1
Liver	12	11	0.106
Lung	17	9
Peritoneum	0	4
Other	4	3
Initial treatment for recurrence2
Resection	8 (26.7)	6 (25.0)	0.623
Chemotherapy	17 (56.7)	16 (66.7)
Other	5 (16.6)	2 (8.3)

¹Duplication (+).

²Number (%) of patients with recurrence.

NAC: Neoadjuvant chemotherapy.

Table 5 Initial treatment strategy for recurrence in high-risk patients

Case	NAC regimen	Course	Efficacy	First recurrence site	Initial treatment for recurrence	Conversion
						Therapy
1	FU, FOL + CDDP	2	SD	Peritoneum	LV/5-FU + CPT-11 (IFL)	Resection
2	FU, FOL + CDDP	2	SD	Liver	LV/5-FU + CPT-11 (IFL)	Resection
3	FU, FOL	2	PD	Other	FOLFOX + Bmab
4	FU, FOL + CDDP	4	SD	Lung	Resection
5	FOLFOX + Bmab	8	PD	Liver	FOLFIRI + Bmab	Resection
6	XELOX + Bmab	14	SD	Lung	IRIS + Bmab
7	FOLFOX + Cmab	6	PR	Liver	Resection
8	IRI + Pmab	6	PR	Peritoneum	IRI + Pmab
9	FOLFIRI + Bmab	6	PR	Liver	FOLFIRI + Bmab

Bmab: Bevacizumab; CDDP: Cisplatin; Cmab: Cetuximab; FOL: Folinic acid; FOLFIRI: Fluorouracil + leucovorin + irinotecan; FOLFOXR: Folinic acid + fluorouracil + oxaliplatin; FU: Fluorouracil; IFL: I-leucovorin + fluorouracil + irinotecan; IRI: Irinotecan; IRIS: Irinotecan + s-1; Pmab: Panitumumab; XELOX: Capecitabine + oxaliplatin; NAC: Neoadjuvant chemotherapy.