Impact of textbook outcome after hepatectomy for colorectal metastases on salvage curative-intent treatment at recurrence

Table 1 Demographics and baseline characteristics, n (%)/mean ± SD/median (interquartile range)

Variables	Total (n = 204)	Non-TO (n = 63)	TO (n = 141)	P value
Gender				0.945
Female	77 (37.75)	24 (38.10)	53 (37.59)
Male	127 (62.25)	39 (61.90)	88 (62.41)
Age, years	58.62 ± 10.43	59.21 ± 10.80	58.36 ± 10.29	0.594
BMI, kg/m2	23.46 ± 3.29	22.96 ± 3.13	23.68 ± 3.34	0.147
Hypertension				0.135
No	127 (62.25)	44 (69.84)	83 (58.87)
Yes	77 (37.75)	19 (30.16)	58 (41.13)
Diabetes				0.597
No	181 (88.73)	57 (90.48)	124 (87.94)
Yes	23 (11.27)	6 (9.52)	17 (12.06)
ASA class				0.945
ASA class I-II	185 (90.69)	57 (90.48)	128 (90.78)
ASA class III	19 (9.31)	6 (9.52)	13 (9.22)
Colorectal cancer
Primary tumor location				0.211
Rectum	91 (44.61)	24 (38.10)	67 (47.52)
Colon	113 (55.39)	39 (61.90)	74 (52.48)
Lymph nodal metastasis				0.957
No	61 (29.90)	19 (30.16)	42 (29.79)
Yes	143 (70.10)	44 (69.84)	99 (70.21)
Tumor grade				0.306
Low	52 (25.49)	19 (30.16)	33 (23.40)
High	152 (74.51)	44 (69.84)	108 (76.60)
CRLM
Surgical approach				< 0.001
Open	53 (25.98)	30 (47.62)	23 (16.31)
Laparoscopic	151 (74.02)	33 (52.38)	118 (83.69)
Major hepatectomy
No	186 (91.18)	53 (84.13)	133 (94.33)	0.018
Yes	18 (8.82)	10 (15.87)	8 (5.67)
Synchronous1				0.012
No	60 (29.41)	11 (17.46)	49 (34.75)
Yes	144 (70.59)	52 (82.54)	92 (65.25)
Distribution				0.844
Unilobar	134 (65.69)	42 (66.67)	92 (65.25)
Bilobar	70 (34.31)	21 (33.33)	49 (34.75)
Simultaneous colorectal resection				< 0.001
No	140 (68.63)	29 (46.03)	111 (78.72)
Yes	64 (31.37)	34 (53.97)	30 (21.28)
Number of lesions	2.00 (1.00, 3.00)	2.00 (1.00, 3.00)	2.00 (1.00, 3.00)	0.762
Max diameter, cm	2.80 (1.95, 4.00)	3.50 (2.20, 4.90)	2.50 (1.60, 3.50)	0.003
CEA, ng/mL	7.89 (3.51, 31.01)	8.82 (3.54, 29.12)	7.89 (3.53, 32.41)	0.429
Adjuvant therapy				0.963
No	49 (24.02)	15 (23.81)	34 (24.11)
Yes	155 (75.98)	48 (76.19)	107 (75.89)
Neoadjuvant therapy				0.005
No	103 (50.49)	41 (65.08)	62 (43.97)
Yes	101 (49.51)	22 (34.92)	79 (56.03)

¹Yes indicates synchronous metastasis, no indicates metachronous metastasis.

TO: Textbook outcome; BMI: Body mass index; ASA: American Society of Anesthesiologists physical status; CRLM: Colorectal liver metastases; CEA: Carcinoembryonic antigen.

Table 2 Distribution of perioperative outcomes, n (%)/median (interquartile range)

Variables	Non-TO (n = 63)	TO (n = 141)	P value
Operation time, minute	240.00 (200.00, 315.00)	182.00 (125.00, 250.00)	< 0.001
Blood loss, mL	200.00 (100.00, 300.00)	100.00 (50.00, 100.00)	< 0.001
Length of stay, days	14.00 (11.50, 21.00)	7.00 (6.00, 9.00)	< 0.001
Blood transfusion			< 0.001
No	49 (77.78)	135 (95.74)
Yes	14 (22.22)	6 (4.26)
R1/R2 resection			0.013
No	59 (93.65)	141 (100.00)
Yes	4 (6.35)	0 (0.00)
Complications (Clavien-Dindo III-IV)			< 0.001
No	32 (50.79)	141 (100.00)
Yes	31 (49.21)	0 (0.00)
Readmission within 90 days			< 0.001
No	49 (77.78)	141 (100.00)
Yes	14 (22.22)	0 (0.00)
Death within 90 days			0.309
No	62 (98.41)	141 (100.00)
Yes	1 (1.59)	0 (0.00)

TO: Textbook outcome.

Table 3 General characteristics of postoperative recurrence, n (%)/median (interquartile range)

Variables	Non-TO (n = 63)	TO (n = 141)	P value
Max diameter, cm	2.70 (1.95, 3.70)	2.40 (1.50, 3.40)	0.244
Recurrence site1			0.002
Intrahepatic	40 (63.49)	117 (82.98)
Intra-and-extrahepatic	23 (36.51)	24 (17.02)
Disease-free interval	3.27 (1.42, 6.90)	7.50 (3.07, 14.50)	< 0.001
Distribution1			0.217
Unilobar	34 (53.97)	89 (63.12)
Bilobar	29 (46.03)	52 (36.88)
Multiple1			0.585
No	19 (30.16)	48 (34.04)
Yes	44 (69.84)	93 (65.96)
SCT1			< 0.001
No	54 (85.71)	74 (52.48)
Yes	9 (14.29)	67 (47.52)

¹Percentage and comparison of those patients who recurred.

TO: Textbook outcome; SCT: Salvage curative-intent treatment.

Table 4 Effect of risk factors on salvage curative-intent treatment by univariable and multivariable analysis

Variables	Univariate		Multivariate
	P value	OR (95%CI)	P value	OR (95%CI)
Gender, male	0.423	1.27 (0.71-2.30)
Age, ≥ 60 years	0.461	0.81 (0.45-1.43)
BMI, ≥ 24 kg/m2	0.845	0.94 (0.53-1.68)
Hypertension	0.838	0.94 (0.52-1.69)
Diabetes	0.121	1.99 (0.83-4.77)
Tumor grade, high	0.901	1.04 (0.54-2.00)
Laparoscopic	0.005	2.89 (1.38-6.04)	0.175	1.77 (0.78-4.02)
Major hepatectomy	0.029	0.19 (0.04-0.85)	0.098	0.26 (0.05-1.28)
Neoadjuvant therapy	0.066	1.71 (0.97-3.04)	0.352	1.35 (0.72-2.51)
Primary tumor location, colon	0.793	1.08 (0.61-1.91)
Lymph nodal metastasis	0.389	1.32 (0.70-2.48)
Synchronous	0.389	1.32 (0.70-2.48)
Multiple	0.416	1.27 (0.71-2.26)
Bilobar	0.558	1.19 (0.66-2.16)
Max diameter, > 3 cm	0.051	0.56 (0.32-1.00)	0.372	0.75 (0.39-1.42)
CEA, ≥ 10 ng/mL	0.806	1.07 (0.61-1.90)
Simultaneous resection	0.034	0.50 (0.26-0.95)	0.255	0.65 (0.31-1.36)
Adjuvant therapy	0.671	1.16 (0.59-2.26)
ASA, class III	0.647	1.25 (0.48-3.26)
TO	< 0.001	5.43 (2.49-11.84)	0.003	3.54 (1.52-8.25)

OR: Odds ratio; CI: Confidence interval; BMI: Body mass index; CEA: Carcinoembryonic antigen; ASA: American Society of Anesthesiologists physical status; TO: Textbook outcome.

Table 5 Univariable and multivariable cox regression analyses of factors associated with overall survival

Variables	Univariate		Multivariate
	P value	HR (95%CI)	P value	HR (95%CI)
Gender, male	0.385	0.81 (0.50-1.30)
Age, ≥ 60 years	0.155	1.40 (0.88-2.23)
BMI, ≥ 24 kg/m2	0.601	0.88 (0.55-1.42)
Hypertension	0.263	0.75 (0.46-1.24)
Diabetes	0.630	1.18 (0.60-2.31)
Tumor grade, high	0.136	0.68 (0.41-1.13)
Laparoscopic	0.529	0.85 (0.51-1.41)
Major hepatectomy	0.047	1.97 (1.01-3.86)	0.200	1.58 (0.79-3.18)
Neoadjuvant therapy	0.005	0.49 (0.30-0.80)	0.055	0.60 (0.36-1.01)
Primary tumor location, colon	0.905	0.97 (0.61-1.56)
Lymph nodal metastasis	0.114	1.57 (0.90-2.73)
Synchronous	0.264	1.37 (0.79-2.40)
Multiple	0.351	0.80 (0.50-1.28)
Bilobar	0.338	0.78 (0.47-1.30)
Max diameter, > 3 cm	0.494	1.18 (0.74-1.87)
CEA, ≥ 10 ng/mL	0.114	1.46 (0.91-2.33)
Simultaneous resection	0.007	1.90 (1.19-3.03)	0.167	1.48 (0.85-2.58)
Adjuvant therapy	0.079	0.62 (0.37-1.06)	0.053	0.58 (0.33-1.01)
ASA, class III	0.917	1.04 (0.50-2.17)
TO	< 0.001	0.44 (0.28-0.70)	0.138	0.66 (0.39-1.14)
SCT1 (time-varying)	0.002	0.38 (0.21-0.71)	0.031	0.50 (0.26-0.94)

¹To strictly account for immortal time bias, salvage curative-intent treatment was modeled as a time-dependent covariate in the multivariable Cox regression analysis.

HR: Hazard ratio; CI: Confidence interval; BMI: Body mass index; CEA: Carcinoembryonic antigen; ASA: American Society of Anesthesiologists physical status; TO: Textbook outcome; SCT: Salvage curative-intent treatment.