Evaluation of prognostic factors and clinicopathological patterns of recurrence after curative surgery for colorectal cancer

Table 1 Complete follow-up program

Time from surgery	Tests
	Full blood count, liver function tests, CEA	Abdominal US	Chest X-Ray	Abdominal CT scan	Colonoscopy
3 mo	√
6 mo	√	√	√
9 mo	√
12 mo	√		√	√	√
18 mo	√
2 yr	√		√	√	√
3 yr	√		√	√	√
4 yr	√	√	√
5 yr	√		√	√	√

CEA: Carcinoembrionyc antigen; US: Ultrasonography; CT: Computed tomography.

Table 2 Potential prognostic factor for disease-free survival and overall survival

	Disease free survival (DFS)			P value	Overall survival (OS)			P value
	3 yr (%)	5 yr (%)	10 y (%)		3 yr (%)	5 yr (%)	10 yr (%)
CEA				0.095				0.045
< 5 ng/mL	84.4	80.8	73.1		88.3	79.8	69.6
≥ 5 ng/mL	72.2	61.1	50.0		81.0	66.7	42.9
AJCC stage				< 0.0001				< 0.0001
1	86.9	82.9	70.6		91.1	83.5	70.4
2	87.7	76.2	57.9		92.9	82.1	54.3
3	59.3	57.9	50.6		72.0	61.0	48.5
4	20.0	-	-		63.6	45.5	18.2
Pathologic M stage1				< 0.0001				0.002
0	77.0	71.2	58.4		85.1	74.4	57.0
1	20.0	-	-		63.6	45.5	18.2
Retrieved LN				0.819				0.688
< 12	81.5	75.4	58.1		87.5	76.4	54.7
≥ 12	73.3	69.3	58.8		83.2	73.8	56.4
LN ratio				0.068				0.043
< 15	66.8	64.0	55.6		78.0	70.7	56.0
≥ 15	41.5	41.5	36.2		61.7	44.7	33.8
Timing of recurrence								0.028
Early (< 3 yr2)					54.9	33.3	11.8
Late (≥ 3 yr2)					100	77.8	22.2

¹According to the tumor node metastasis staging system.

²Recurrence from the first treatment.

CEA: Carcinoembryonic antigen; AJCC: American Joint Committee on Cancer; LN: Lymph node.

Table 3 Recurrence characteristics and related treatment

	Total, n = 234	%
Recurrence
No	174	67.7
Yes	60	23.3
Timing of recurrence1
< 3 yr	51	19.8
≥ 3 yr	9	3.5
Liver recurrence
No	207	80.5
Yes	25	9.7
Missing	2	9.7
Lung recurrence
No	216	84.0
Yes	16	6.2
Missing	2	9.7
Local recurrence
No	215	83.7
Yes	17	6.6
Missing	2	9.7
Peritoneal seeding
No	225	87.5
Yes	7	2.7
Missing	2	9.7
Treatment of the first recurrence
Surgery	25	41.7
Chemotherapy	20	33.3
Best supportive care	8	13.3
Palliation	2	3.3
Missing	5	8.3

¹Recurrence from the first treatment.

Table 4 Demographic and patient-related preoperative potential prognostic factors for recurrence and evaluation of early vs late recurrence (univariate analysis)

	Recurrence, n = 234					Timing of recurrence, n = 60
	All	No	Yes	HR (95%CI)	P value	Early recurrence (< 3 yr)	Late recurrence (≥ 3 yr)	OR (95%CI)	P value
	n (%)	n = 174 (67.7%)	n = 60 (23.3%)			n = 51 (85.0%)	n = 9 (15.0%)
Age, yr; mean ± SD	68 ± 12	68 ± 11	69 ± 12	1.00 (0.98-1.02)	0.868	67 ± 12	77 ± 8	1.10 (1.00-1.21)	0.050
Gender, n (%)					0.179				0.421
Male	128 (54.7)	99 (77.3)	29 (22.6)	Reference		25 (86.2)	4 (13.8)	Reference
Female	106 (45.3)	75 (70.7)	31 (29.2)	1.42 (0.85-2.37)		26 (83.9)	5 (16.1)	1.85 (0.41-8.21)
Preop Hb, g/dL, mean ± SD	12.3 ± 2.1	12.6 ± 2.1	11.6 ± 2.3	0.84 (0.71-1.01)	0.058	11.9 ± 2.2	9.67 ± 2.3	0.60 (0.31-1.17)	0.136
Preop glycemia, g/dL, mean ± SD	0.99 ± 0.26	0.96 ± 0.24	1.08 ± 0.31	3.44 (1.05-11.24)	0.040	1.10 ± 0.34	0.99 ± 0.19	0.25 (0.00-16.06)	0.518
Preop total proteins, g/dL, mean ± SD	6.8 ± 0.7	6.8 ± 0.6	6.8 ± 1	1.07 (0.54-2.11)	0.839	6.7 ± 1.0	7.3 ± 0.2	2.43 (0.47-12.54)	0.288
Preop CEA, n (%)					0.029				0.440
< 5 ng/mL	85 (82.5)	71 (83.5)	14 (16.5)	0.36 (0.15-0.90)		12 (85.7)	2 (14.3)	Reference
≥ 5 ng/mL	18 (17.5)	11 (61.1)	7 (38.9)	Reference		5 (71.4)	2 (28.6)	2.40 (0.26-22.10)
Missing	131	131				39
BMI, mean ± SD	26 ± 4	25 ± 4	27 ± 5	1.06 (0.99-1.14)	0.085	27 ± 5	27 ± 5	0.98 (0.81-1.19)	0.866
ASA, n (%)
1	31 (14.5)	26 (83.9)	5 (16.1)	Reference		5 (100)	0 (0)	Reference
2	80 (37.4)	61 (76.2)	19 (23.8)	1.50 (0.56-4.02)	0.421	16 (84.2)	3 (15.8)	-	0.951
3	94 (43.9)	72 (76.6)	22 (23.4)	1.51 (0.57-3.40)	0.404	16 (72.7)	6 (27.3)	-	0.948
4	9 (4.2)	5 (55.6)	4 (44.4)	3.85 (1.03-14.41)	0.045	4 (100)	0 (0)	-	1.000
Missing	20	20				10
Presentation with occlusion, n (%)					0.021				0.366
No	42 (59.2)	33 (78.6)	9 (21.4)	Reference		7 (77.8)	2 (22.2)	Reference
Yes	29 (40.8)	15 (51.7)	14 (48.3)	2.60 (1.15-5.87)		13 (92.9)	1 (7.1)	0.31 (0.02-3.97)
Missing	163	163				37
Tumor site, n (%)
Right colon	70 (29.9)	53 (75.7)	17 (24.3)	Reference		13 (76.5)	4 (23.5)	Reference
Left colon	103 (44)	76 (73.8)	27 (26.2)	0.93 (0.50-1.70)	0.807	24 (88.9)	3 (11.1)	0.41 (0.08-2.10)	0.282
Rectum	61 (26.1)	45 (73.8)	16 (26.2)	0.94 (0.47-1.85)	0.851	14 (87.5)	2 (12.5)	0.46 (0.07-2.98)	0.418

HR: Hazard ratio; OR: Odds ratio; CI: Confidential intervals; Preop: Preoperative value; Hb: Haemoglobin; CEA: Carcinoembryonic antigen; BMI: Body mass index; ASA: American Society of Anaesthesiologists Score.

Table 5 Treatment-related potential prognostic factors for recurrence and evaluation of early versus late recurrence (univariate analysis)

	Recurrence, n = 234					Timing of recurrence, n = 60
	All	No	Yes	HR (95%CI)	P value	Early recurrence (< 3 yr)	Late recurrence (≥ 3 yr)	OR (95%CI)	P value
	n, %	n = 174 (67.7%)	n = 60 (23.3%)			n = 51 (85.0%)	n = 9 (15.0%)
Neoadjuvant therapy, n (%)					0.921				0.949
No	97 (93.3)	68 (70)	29 (30)	Reference		25 (86.2)	4 (13.8)	Reference
Yes	7 (6.7)	5 (71)	2 (29)	1.07 (0.26-4.51)		2 (100)	0 (0)	1.13 (0.02-53.57)
Missing	130	130				29
Surgery, n (%)
Right emicolectomy	55 (23.5)	42 (76.4)	13 (23.6)	Reference		10 (76.9)	3 (23.1)	Reference
Extended right emicolectomy	15 (6.4)	12 (80)	3 (20)	1.16 (0.37-3.59)	0.801	2 (66.7)	1 (33.3)	4.20 (0.37-47.64)	0.247
Intermediate colectomy	10 (4.3)	6 (60)	4 (40)	2.16 (0.70-6.71)	0.182	3 (75)	1 (25)	1.80 (0.14-23.6)	0.655
AR/Hartmann	106 (45.3)	80 (75.5)	26 (24.5)	1.09 (0.55-2.17)	0.798	24 (92.3)	2 (7.7)	0.43 (0.06-3.02)	0.395
LAR/Miles	38 (16.2)	28 (73.7)	10 (26.3)	1.16 (0.50-2.68)	0.731	8 (80)	2 (20)	1.23 (0.16-9.69)	0.841
Total/Sub-total Colectomy	6 (2.6)	3 (50)	3 (50)	2.69 (0.76-9.53)	0.126	3 (100)	0 (0.0)	0.60 (0.01-24.50)	0.787
Segmental resection	4 (1.7)	3 (75)	1 (25)	1.12 (0.14-8.68)	0.916	1 (100)	0 (0.0)	1.7 (0.02-162.35)	0.819
Associated procedure, n (%)
No	52 (50.5)	39 (75)	13 (25)	Reference		11 (84.6)	2 (15.4)	Reference
Minor	40 (38.8)	27 (67.5)	13 (32.5)	1.30 (0.60-2.80)	0.505	11 (84.6)	2 (15.4)	1.00 (0.13-7.44)	1.00
Major	11 (10.7)	4 (36.4)	7 (63.6)	3.56 (1.41-8.96)	0.007	7 (100)	0 (0)	0.31 (0.01-8.95)	0.492
Missing	131	131				27
Operative technique, n (%)					< 0.001				0.061
Open	99 (42.7)	61 (61.6)	38 (38.4)	Reference		35 (92.1)	3 (7.9)	Reference
Laparoscopy	133 (57.3)	111 (83.5)	22 (16.5)	0.37 (0.22-0.62)		16 (72.7)	6 (27.3)	4.00 (0.94-17.01)
Missing	2	2				-
Duration of surgery, min – mean ± SD	232 ± 67	230 ± 61	239 ± 83	1.00 (0.99-1.01)	0.496	238 ± 78	242 ± 112	1.00 (0.99-1.01)	0.808
Postop blood transfusion, n (%)					0.123				0.119
No	174 (75.7)	134 (77)	40 (23)	Reference		36 (90)	4 (10)	Reference
Yes	56 (24.3)	37 (66.1)	19 (33.9)	1.54 (0.89-2.66)		14 (73.7)	5 (26.3)	3.08 (0.75-12.64)
Missing	4	4				1
Reoperation, n (%)					0.262				0.559
No	82 (91.1)	60 (73.2)	22 (26.8)	Reference		17 (77.3)	5 (22.7)	Reference
Yes	8 (8.9)	5 (62.5)	3 (37.5)	1.99 (0.60-6.61)		2 (66.7)	1 (33.3)	2.13 (0.17-26.68)
Missing	144	144				35
Hospital stay, d, mean ± SD	9.2 ± 6	8.7 ± 3.7	10.9 ± 9.1	1.05 (1.02-1.07)	0.001	10.9 ± 9.8	10.6 ± 4.0	1.01 (0.95-1.08)	0.737
Adjuvant therapy, n (%)					0.064				0.057
No	127 (56.4)	103 (81.1)	24 (18.9)	Reference		18 (75)	6 (25)	Reference
Yes	98 (43.5)	67 (68.4)	31 (31.6)	1.65 (0.97-2.81)		28 (90.3)	3 (9.7)	0.22 (0.04-1.04)
Missing	9	9				5
Start of adj CHT, n (%)					0.268				0.401
< 6 wk	26 (48.1)	13 (50)	13 (50)	Reference		12 (92.3)	1 (7.7)	Reference
≥ 6 wk	28 (51.9)	19 (67.9)	9 (32.1)	1.63 (0.69-3.95)		8 (88.9)	1 (11.1)	4.4 (0.14-141.01)
Missing	180	180				38

HR: Hazard ratio; OR: Odds ratio; CI: Confidential intervals; AR: Anterior resection of the rectum; LAR: Low anterior resection of the rectum; Adj CHT: Adjuvant chemotherapy.

Table 6 Pathological-related potential prognostic factors for recurrence and evaluation of early versus late recurrence (univariate analysis)

	Recurrence, n = 234					Timing of recurrence, n = 60
	All	No	Yes	HR (95%CI)	P value	Early recurrence (< 3 yr)	Late recurrence (≥ 3 yr)	OR (95%CI)	P value
	n (%)	n = 174 (67.7%)	n = 60 (23.3%)			n = 51 (85.0%)	n = 9 (15.0%)
Major tumor diameter, mm, mean ± SD	43 ± 23	41.6 ± 23	46.8 ± 24.5	1.01 (0.99-1.02)	0.130	47.6 ± 23.5	42.8 ± 29.8	0.99 (0.96-1.02)	0.694
Pathological T stage1, n (%)
1	46 (19.7)	44 (95.7)	2 (4.3)	Reference		2 (100)	0 (0)	Reference
2	40 (17.2)	32 (80)	8 (20)	3.44 (0.91-12.99)	0.068	6 (75)	2 (25)	0.64 (0.04-10.57)	0.756
3	141 (60.5)	94 (66.7)	47 (33.3)	6.14 (1.91-19.77)	0.002	40 (85.1)	7 (14.9)	0.27 (0.02-3.20)	0.298
4	6 (2.6)	4 (66.7)	2 (33.3)	6.19 (1.03-37.96)	0.046	2 (100)	0 (0)	0.33 (0.00-24.94)	0.624
Missing	1	1				1
Pathological N stage1, n (%)
0	155 (66.5)	129 (83.2)	26 (16.8)	Reference		18 (69.2)	8 (30.8)	Reference
1	51 (21.9)	36 (70.6)	15 (29.4)	1.95 (1.03-3.69)	0.039	15 (100)	0 (0)	0.07 (0.00-1.44)	0.085
2	27 (11.6)	9 (33.3)	18 (66.7)	6.35 (3.50-11.64)	< 0.001	17 (94.4)	1 (5.6)	0.19 (0.03-1.25)	0.084
Missing	1	1				1
Pathological M stage1, n (%)					< 0.001				0.408
0	223 (95.6)	171 (76.7)	52 (23.3)	Reference		43 (82.7)	9 (17.3)	Reference
1	10 (4.3)	2 (20)	8 (80)	5.31 (2.50-11.30)		8 (100)	0 (0)	0.27 (0.01-6.02)
Missing	1	1				-
AJCC stage, n (%)
1	77 (32.9)	68 (88.3)	9 (11.7)	Reference		7 (77.8)	2 (22.2)	Reference
2	75 (32)	59 (78.7)	16 (21.3)	1.65 (0.74-3.67)	0.220	10 (62.5)	6 (37.5)	1.12 (0.20-6.17)	0.894
3	72 (30.8)	45 (62.5)	27 (37.5)	3.59 (1.73-7.42)	< 0.001	26 (96.3)	1 (3.7)	0.12 (0.01-1.03)	0.053
4	10 (4.3)	2 (20)	8 (80)	11.1 (4.35-28.52)	< 0.001	8 (100)	0 (0)	0.13 (0.00-3.43)	0.220
Retrieved LN, n (%)					0.535				0.741
< 12	65 (29.3)	53 (81.5)	12 (18.5)	Reference		10 (83.3)	2 (16.7)	Reference
≥ 12	157 (70.7)	112 (71.3)	45 (28.7)	0.84 (0.47-1.47)		38 (84.4)	7 (15.6)	0.78 (0.18-3.40)
Missing	12	12				3
LN ratio, mean ± SD	20 ± 16	16 ± 13	25 ± 19	25.8 (8.22-80.93)	< 0.001	25 ± 19	22	0.00 (0.00-2.20)	0.073
Colloid component, n (%)					0.168				0.607
No	63 (60)	49 (77.8)	14 (22.2)	Reference		12 (85.7)	2 (14.3)	Reference
Yes	42 (40)	27 (64.3)	15 (35.7)	1.68 (0.80-3.53)		13 (86.7)	2 (13.3)	0.55 (0.06-5.22)
Missing	129	129				31

¹According to the tumor node metastasis staging system.

AJCC: American Joint Committee on Cancer; LN: Lymph nodes; HR: Hazard ratio; OR: Odds ratio; CI: Confidential intervals.

Table 7 Multivariate analysis of potential prognostic factors for recurrence

	HR	95%CI	P value
Hospital stay, d	1.053	1.023-1.084	< 0.001
Pathological N stage1
0	Reference
1	1.608	0.773-3.343	0.204
2	6.129	3.070-12.236	< 0.001
Pathological M stage1
0	Reference
1	5.521	2.113-14.425	< 0.001

¹According to the tumor node metastasis staging system.

HR: Hazard ratio; CI: Confidential intervals.

Table 8 Demographic and patient-related preoperative potential prognostic factors for liver and lung recurrence

	Recurrence, n = 58
	Liver				Lung
	No, n = 33 (55.0%)	Yes, n = 25 (41.7%)	HR (95%CI)	P value	No, n = 42 (70.0%)	Yes, n = 16 (26.7%)	HR (95%CI)	P value
Age, yr, mean ± SD	67.4 ± 12.3	68.0 ± 12.3	1.00 (0.97-1.03)	0.945	67.3 ± 12.7	68.7 ± 11.0	1.00 (0.96-1.04)	0.837
Gender, n (%)				0.702				0.185
Male	16 (55.2)	13 (44.8)	Reference		19 (65.5)	10 (34.5)	Reference
Female	17 (58.6)	12 (41.4)	0.86 (0.39-1.88)		23 (79.3)	6 (20.7)	0.50 (0.18-1.39)
Preop Hb, g/dL, mean ± SD	11.28	11.93	1.16 (0.88-1.53)	0.296	11.4 ± 2.3	12.0 ± 2.5	1.14 (0.81-1.61)	0.446
Preop glycemia, g/dL, mean ± SD	1.08 ± 0.36	1.08 ± 0.31	1.72 (0.14-10.00)	0.884	1.06 ± 0.33	1.14 ± 0.35	1.47 (0.12-18.20)	0.764
Preop total proteins, g/dL, mean ± SD	6.7 ± 0.7	7.1 ± 0.8	1.33 (0.56-3.17)	0.514	6.9 ± 0.9	6.9 ± 0.5	0.87 (0.19-3.93)	0.861
Preop CEA, n (%)				0.868				0.891
< 5 ng/mL	6 (46.2)	7 (53.8)	Reference		10 (76.9)	3 (23.1)	Reference
≥ 5 ng/mL	4 (57.1)	3 (42.9)	0.89 (0.23-3.46)		5 (71.4)	2 (28.6)	1.14 (0.18-7.14)
Missing	23	15			27	11
BMI, mean ± SD	26.3 ± 4.9	27.8 ± 4.7	1.04 (0.94-1.15)	0.465	27.6 ± 4.8	25.7 ± 4.6	0.96 (0.83-1.13)	0.646
ASA, n (%)
1	3 (60)	2 (40)	Reference		4 (80)	1 (20)	Reference
2	8 (42.1)	11 (57.9)	0.64 (0.15-2.75)	0.544	14 (73.7)	5 (26.3)	0.46 (0.06-3.38)	0.447
3	13 (61.9)	8 (38.1)	0.34 (0.07-1.55)	0.163	15 (71.4)	6 (28.6)	0.31 (0.04-2.35)	0.258
4	3 (100)	0 (0.0)	0.30 (0.01-7.69)	0.471	2 (66.7)	1 (33.3)	2.09 (0.16-27.56)	0.573
Missing	6	4			7	3
Presentation with occlusion, n (%)				0.465				0.470
No	5 (62.5)	3 (37.5)	Reference		6 (75)	2 (25)	Reference
Yes	6 (46.2)	7 (53.8)	1.58 (0.46-5.44)		9 (69.2)	4 (30.8)	1.89 (0.34-10.61)
Missing	23	15			27	11
Tumour site, n (%)
Right colon	11 (68.7)	5 (31.3)	Reference		13 (81.3)	3 (18.7)	Reference
Left colon	11 (42.3)	15 (57.7)	2.48 (0.89-6.88)	0.081	20 (76.9)	6 (23.1)	1.73 (0.42-7.04)	0.445
Rectum	11 (68.7)	5 (31.3)	0.98 (0.28-3.41)	0.972	9 (56.3)	7 (43.7)	2.34 (0.59-9.32)	0.226

HR: Hazard ratio; OR: Odds ratio; CI: Confidential intervals; Preop: Preoperative value; Hb: Haemoglobin; CEA: Carcinoembryonic antigen; BMI: Body mass index; ASA: American Society of Anaesthesiologists Score.

Table 9 Treatment-related potential prognostic factors for liver and lung recurrence

	Recurrence, n = 58
	Liver				Lung
	No, n = 33 (55.0%)	Yes, n = 25 (41.7%)	HR (95%CI)	P value	No, n = 42 (70.0%)	Yes, n = 16 (26.7%)	HR (95%CI)	P value
Neoadjuvant therapy, n (%)				0.952				0.010
No	13 (46.4)	15 (53.6)	Reference		21 (75)	7 (25)	Reference
Yes	2 (100)	0 (0)	0.91 (0.04-18.42)		0 (0)	2 (100)	13.21 (1.86-93.92)
Missing	18	10			21	7
Surgery, n (%)
Right emicolectomy	10 (83.3)	2 (16.7)	Reference		10 (83.3)	2 (16.7)	Reference
Extended right emicolectomy	1 (33.3)	2 (66.7)	2.02 (0.31-13.21)	0.461	2 (66.7)	1 (33.3)	0.81 (0.09-7.66)	0.857
Intermediate colectomy	0 (0)	4 (100)	7.05 (1.34-36.94)	0.021	4 (100)	0 (0)	0.75 (0.03-21.49)	0.864
AR/Hartmann’s procedure	11 (44)	14 (56)	2.44 (0.59-10.18)	0.220	19 (76)	6 (24)	1.07 (0.21-5.39)	0.936
Low anterior resection/Miles	9 (90)	1 (10)	0.54 (0.06-4.67)	0.579	3 (30)	7 (70)	2.20 (0.45-10.78)	0.332
Total/Sub-total colectomy	2 (66.7)	1 (33.3)	2.37 (0.27-20.60)	0.433	3 (100)	0 (0)	0.84 (0.03-24.19)	0.920
Segmental resection	0 (0)	1 (100)	110 (5.3-2304.7)	0.002	1 (100)	0 (0)	-	-
Associated procedure, n (%)
No	4 (33.3)	8 (66.7)	Reference		10 (83.3)	2 (16.7)	Reference
Minor	9 (69.2)	4 (30.8)	0.37 (0.11-1.23)	0.106	10 (76.9)	3 (23.1)	0.92 (0.16-5.43)	0.928
Major	2 (28.6)	5 (71.4)	1.65 (0.53-5.47)	0.377	4 (57.1)	3 (42.9)	3.37 (0.55-20.65)	0.188
Missing	18	8			18	8
Operative technique, n (%)				0.253				0.658
Open	19 (51.4)	18 (48.6)	Reference		27 (73)	10 (27)	Reference
Laparoscopy	14 (66.7)	7 (33.3)	0.60 (0.25-1.44)		15 (71.4)	6 (28.6)	0.79 (0.28-2.24)
Duration of surgery, min, mean ± SD	250 ± 90	227 ± 75	1.00 (0.99-1.00)	0.579	231 ± 83	264 ± 86	1.00 (1.00-1.01)	0.221
Hospital stay, d, mean ± SD	10.0 ± 3.9	9.5 ± 2.1	0.97 (0.84-1.11)	0.637	9.8 ± 2.8	9.9 ± 4.3	1.00 (0.86-1.17)	0.980
Postoperative blood transfusion, n (%)				0.067				0.992
No	20 (50)	20 (50)	Reference		30 (75)	10 (25)	Reference
Yes	13 (76.5)	4 (23.5)	0.37 (0.12-1.07)		11 (64.7)	6 (35.3)	0.99 (0.36-2.75)
Missing	-	1			1	-
Reoperation due to complications, n (%)				0.723				0.705
No	12 (57.1)	9 (42.9)	Reference		18 (85.7)	3 (14.3)	Reference
Yes	2 (100)	0 (0)	0.58 (0.03-12.07)		1 (50)	1 (50)	1.53 (0.17-13.57)
Missing	19	16			23	12
Adjuvant therapy, n (%)				0.055				0.703
No	16 (72.7)	6 (27.2)	Reference		15 (68.2)	7 (31.8)	Reference
Yes	14 (45.2)	17 (54.8)	2.52 (0.98-6.48)		23 (74.2)	8 (25.8)	1.23 (0.42-3.62)
Missing	3	2			4	1
Start of adj CHT, n (%)				0.913				0.344
< 6 wk from surgery	6 (46.2)	7 (53.8)	Reference		8 (61.5)	5 (38.6)	Reference
≥ 6 wk from surgery	4 (44.4)	5 (55.6)	1.07 (0.33-3.43)		8 (88.9)	1 (11.1)	0.35 (0.04-1.04)
Missing	23	13			26	10

HR: Hazard ratio; OR: Odds ratio; CI: Confidential intervals; Adj CHT: Adjuvant chemotherapy.

Table 10 Pathological-related potential prognostic factors for liver and lung recurrence

	Recurrence, n = 58
	Liver				Lung
	No, n = 33 (55.0%)	Yes, n = 25 (41.7%)	HR (95%CI)	P value	No, n = 42 (70.0%)	Yes, n = 16 (26.7%)	HR (95%CI)	P value
Major tumor diameter, mm, mean ± SD	55.71	42.74	0.99 (0.98-1.01)	0.368	29.09	30.01	0.99 (0.97-1.01)	0.326
Pathological T stage1, n (%)
1	1 (50)	1 (50)	Reference		1 (50)	1 (50)	Reference
2	6 (75)	2 (25)	0.68 (0.06-7.50)	0.752	6 (75)	2 (25)	0.77 (0.07-8.58)	0.835
3	25 (55.6)	20 (44.4)	1.66 (0.22-12.44)	0.623	33 (73.3)	12 (26.7)	1.52 (0.19-12.45)	0.695
4	1 (50)	1 (50)	2.18 (0.13-35.75)	0.585	1 (50)	1 (50)	4.28 (0.24-76.14)	0.981
Missing	-	-			1	-
Pathological N stage1, n (%)
0	17 (65.4)	9 (34.6)	Reference		18 (69.2)	8 (30.8)	Reference
1	9 (64.3)	5 (35.7)	1.75 (0.55-5.53)	0.341	10 (71.4)	4 (28.6)	2.31 (0.60-8.88)	0.222
2	7 (41.2)	10 (58.8)	3.48 (1.31-9.27)	0.013	13 (76.5)	4 (23.5)	2.17 (0.57-8.51)	0.264
Missing	-	1			1	-
Pathological M stage1, n (%)				0.321				0.092
0	29 (58)	21 (42)	Reference		37 (74)	13 (26)	Reference
1	4 (50)	4 (50)	1.74 (0.58-5.22)		5 (62.5)	3 (37.5)	3.13 (0.83-11.79)
AJCC stage, n (%)
1	7 (77.8)	2 (22.2)	Reference		6 (66.7)	3 (33.3)	Reference
2	10 (62.5)	6 (37.5)	2.12 (0.43-10.51)	0.359	11 (68.7)	5 (31.3)	1.45 (0.33-6.33)	0.623
3	12 (48)	13 (52)	5.09 (1.10-23.52)	0.037	20 (80)	5 (20)	2.11 (0.42-10.47)	0.361
4	4 (50)	4 (50)	5.57 (0.96-32.24)	0.055	5 (62.5)	3 (37.5)	3.06 (0.85-30.09)	0.075
Retrieved LN, n (%)				0.803				0.961
< 12	6 (54.5)	5 (45.5)	Reference		8 (72.7)	3 (27.3)	Reference
≥ 12	26 (59.1)	18 (40.9)	0.90 (0.38-2.12)		31 (70.5)	13 (29.5)	0.97 (0.34-2.82)
Missing	1	2			3	-
LN ratio, mean ± SD	22 ± 18	28 ± 20	4.21 (0.79-22.42)	0.092	27 ± 21	18 ± 8	1.07 (0.96-18.11)	0.963
Colloid component, n (%)				0.367				0.200
No	6 (46.2)	7 (53.8)	Reference		8 (61.5)	5 (38.5)	Reference
Yes	11 (73.3)	4 (26.7)	0.56 (0.16-1.98)		14 (93.3)	1 (6.7)	0.24 (0.03-2.12)
Missing	16	14			20	10

¹According to the tumor node metastasis staging system. HR: Hazard ratio; CI: Confidential intervals; AJCC: American Joint Committee on Cancer; LN: Lymph nodes.

Table 11 Demographic and patient-related preoperative potential prognostic factors for local and peritoneal recurrence

	Recurrence, n = 58
	Peritoneal				Local
	No, n = 51 (87.9%)	Yes, n = 7 (12.1%)	HR (95%CI)	P value	No, n = 41 (70.7%)	Yes, n = 17 (29.3%)	HR (95%CI)	P value
Age, yr, mean ± SD	67.6 ± 11.9	66.3 ± 14.9	0.98 (0.92-1.04)	0.489	68.6 ± 11.3	67.5 ± 14.2	0.98 (0.95-1.02)	0.345
Gender, n (%)				0.434				0.862
Male	27 (93.1)	2 (6.9)	Reference		21 (72.4)	8 (27.6)	Reference
Female	24 (82.8)	5 (17.2)	1.97 (0.36-10.77)		20 (69)	9 (31)	0.91 (0.32-2.61)
Preop Hb, g/dL, mean ± SD	11.7 ± 2.3	11.1 ± 2.7	0.91 (0.55-1.50)	0.712	11.9 ± 2.2	9.9 ± 1.9	0.71 (0.38-1.31)	0.273
Preop glycemia, g/dL, mean ± SD	1.08 ± 0.32	1.08 ± 0.41	2.42 (0.05-123.6)	0.659	1.12 ± 0.33	0.82 ± 0.16	-	0.210
Preop total proteins, g/dL, mean ± SD	7.0 ± 0.7	6.5 ± 1.1	0.17 (0.02-1.23)	0.079	6.9 ± 0.9	7.0 ± 0.4	0.60 (0.02-14.06)	0.750
Preop CEA, n (%)				0.727				0.860
< 5 ng/mL	11 (84.6)	2 (15.4)	Reference		12 (92.3)	1 (7.7)	Reference
≥ 5 ng/mL	6 (85.7)	1 (14.3)	0.52 (0.01-21.28)		5 (71.4)	2 (28.6)	1.32 (0.06-29.55)
Missing	34	4			24	14
BMI, mean ± SD	26.7 ± 4.5	30.7 ± 7.2	1.15 (0.91-1.44)	0.238	27.4 ± 5.1	26.0 ± 3.6	0.95 (0.81-1.11)	0.510
ASA, n (%)
1	4 (80)	1 (20)	Reference		4 (80)	1 (20)	Reference
2	17 (89.5)	2 (10.5)	0.25 (0.02-2.83)	0.264	15 (78.9)	4 (21.1)	0.42 (0.06-3.18)	0.401
3	18 (85.7)	3 (14.3)	0.19 (0.02-2.14)	0.178	14 (66.7)	7 (33.3)	0.35 (0.05-2.61)	0.307
4	3 (100)	0 (0)	0.47 (0.01-23.31)	0.707	1 (33.3)	2 (66.7)	2.32 (0.24-21.92)	0.464
Missing	9	1			7	3
Presentation with occlusion, n (%)				0.674				0.962
No	7 (87.5)	1 (12.5)	Reference		6 (75)	2 (25)	Reference
Yes	11 (84.6)	2 (15.4)	1.67 (0.15-18.56)		12 (92.3)	1 (7.7)	0.93 (0.06-15.21)
Missing	33	4			23	14
Tumour site, n (%)
Right colon	14 (87.5)	2 (12.5)	Reference		9 (56.3)	7 (43.7)	Reference
Left colon	24 (92.3)	2 (7.7)	0.80 (0.11-5.70)	0.825	19 (73.1)	7 (26.9)	0.79 (0.27-2.30)	0.671
Rectum	13 (81.2)	3 (18.8)	1.36 (0.23-8.17)	0.735	13 (81.3)	3 (18.7)	0.44 (0.11-1.69)	0.232

HR: Hazard ratio; OR: Odds ratio; CI: Confidential intervals; Preop: Preoperative value; Hb: Haemoglobin; CEA: Carcinoembryonic antigen; BMI: Body mass index; ASA: American Society of Anaesthesiologists Score.

Table 12 Treatment-related potential prognostic factors for local and peritoneal recurrence

	Recurrence, n = 58
	Peritoneal				Local
	No, n = 51 (87.9%)	Yes, n = 7 (12.1%)	HR (95%CI)	P value	No, n = 41 (70.7)	Yes, n = 17 (29.3)	HR (95%CI)	P value
Neoadjuvant therapy, n (%)				0.569				0.475
No	23 (82.1)	5 (17.9)	Reference		23 (81.1)	5 (17.9)	Reference
Yes	2 (100)	0 (0)	2.71 (0.09-84.27)		2 (100)	0 (0)	3.88 (0.09-160.22)
Missing	26	2			16	12
Surgery, n (%)
Right emicolectomy	10 (83.3)	2 (16.7)	Reference		6 (50)	6 (50)	Reference
Extended right emicolectomy	3 (100)	0 (0)	0.23 (0.01-11.90)	0.468	2 (66.7)	1 (33.3)	0.20 (0.02-1.68)	0.140
Intermediate colectomy	4 (100)	0 (0)	1.20 (0.03-47.50)	0.923	4 (100)	0 (0)	0.35 (0.01-8.18)	0.511
AR/Hartmann’s procedure	23 (92)	2 (8)	0.36 (0.04-3.04)	0.350	17 (68)	8 (32)	0.41 (0.13-1.29)	0.127
Low Anterior resection/Miles	8 (80)	2 (20)	0.68 (0.07-6.27)	0.731	9 (90)	1 (10)	0.15 (0.02-1.07)	0.059
Total/Sub-total colectomy	2 (66.7)	1 (33.3)	2.99 (0.25-35.10)	0.383	2 (66.7)	1 (33.3)	0.98 (0.14-6.95)	0.981
Segmental resection	1 (100)	0 (0)	-	-	1 (100)	0 (0)	-	-
Associated procedure, n (%)
No	11 (91.7)	1 (8.3)	Reference		11 (91.7)	1 (8.3)	Reference
Minor	11 (84.6)	2 (15.4)	1.16 (0.10-14.11)	0.905	7 (53.8)	6 (46.2)	2.41 (0.33-17.37)	0.384
Major	7 (100)	0 (0)	0.61 (0.01-31.26)	0.808	5 (71.4)	2 (28.6)	3.26 (0.36-29.71)	0.295
Missing	22	4			18	8
Operative technique, n (%)				0.128				0.368
Open	35 (94.6)	2 (5.4)	Reference		25 (67.6)	12 (32.4)	Reference
Laparoscopy	16 (76.2)	5 (23.8)	3.64 (0.69-19.14)		16 (76.2)	5 (23.8)	0.61 (0.21-1.77)
Duration of surgery, min, mean ± SD	239 ± 85	249 ± 87	1.00 (0.99-1.01)	0.869	244 ± 81	232 ± 93	1.00 (0.99-1.01)	0.934
Hospital stay, d, mean ± SD	9.8 ± 3.2	10.0 ± 4.1	0.98 (0.76-1.27)	0.907	9.4 ± 3.3	10.7 ± 3.1	1.09 (0.96-1.23)	0.181
Postoperative blood transfusion, n (%)				0.272				0.518
No	37 (92.5)	3 (7.5)	Reference		30 (75)	10 (25)	Reference
Yes	13 (76.5)	4 (23.5)	2.32 (0.52-10.38)		10 (58.8)	7 (41.2)	1.39 (0.51-3.74)
Missing	1	-			1	-
Reoperation due to complications, n (%)				0.344				0.182
No	17 (81)	4 (19)	Reference		18 (75)	6 (25)	Reference
Yes	1 (50)	1 (50)	3.00 (0.31-29.24)		1 (50)	1 (50)	4.35 (0.50-37.59)
Missing	33	2			22	10
Adjuvant therapy, n (%)				0.481				0.852
No	20 (90.9)	2 (9.1)	Reference		14 (63.6)	8 (36.4)	Reference
Yes	28 (90.3)	3 (9.7)	2.26 (0.23-21.77)		23 (74.2)	8 (25.8)	1.11 (0.38-3.21)
Missing	3	2			4	1
Start of adj chemotherapy, n (%)				0.648				0.953
< 6 wk from surgery	12 (92.3)	1 (7.7)	Reference		9 (69.2)	4 (30.8)	Reference
≥ 6 wk from surgery	8 (88.8)	1 (11.1)	1.91 (0.12-30.85)		7 (77.8)	2 (22.2)	0.95 (0.18-5.13)
Missing	31	5			25	1

HR: Hazard ratio; OR: Odds ratio; CI: Confidential intervals; Adj: Adjuvant.

Table 13 Pathological-related potential prognostic factors for local and peritoneal recurrence

	Recurrence, n = 58
	Peritoneal				Local
	No, n = 51 (87.9)	Yes, n = 7 (12.1)	HR (95%CI)	P value	No, n = 41 (70.7)	Yes, n = 17 (29.3)	HR (95%CI)	P value
Major tumor diameter, mm, mean ± SD	46.2 ± 22.4	64.0 ± 35.1	1.02 (0.99-1.05)	0.062	44.2 ± 19	55.8 ± 31.9	1.01 (0.99-1.03)	0.107
Pathological T stage1, n (%)
1	2 (100)	0 (0)	Reference		2 (100)	0 (0)	Reference
2	7 (87.5)	1 (12.5)	1.41 (0.03-62.92)	0.858	4 (50)	4 (50)	4.91 (0.19-124)	0.335
3	39 (86.7)	6 (13.3)	3.8 (0.05-270.74)	0.538	33 (73.3)	12 (23.7)	6.29 (0.22-177)	0.281
4	2 (100)	0 (0)	7.03 (0.04-1358)	0.468	1 (50)	1 (50)	21.47 (0.51-897)	0.107
Missing	1	-			1	-
Pathological N stage1, n (%)				0.196
0	25 (96.2)	1 (3.8)	Reference		17 (65.4)	9 (34.6)	Reference
1	11 (78.6)	3 (21.4)	14.5 (0.52-405.2)	0.115	8 (57.1)	6 (42.9)	2.41 (0.76-7.65)	0.135
2	14 (82.4)	3 (17.6)	15.4 (0.55-428)	0.107	15 (88.2)	2 (11.8)	0.88 (0.19-4.11)	0.874
Missing	1	-			1	-
Pathological M stage1, n (%)				0.546				0.032
0	44 (88)	6 (12)	Reference		37 (74)	13 (26)	Reference
1	7 (87.5)	1 (12.5)	1.84 (0.25-13.22)		4 (50)	4 (50)	3.57 (1.12-11.40)
AJCC Stage, n (%)
1	8 (88.9)	1 (11.1)	Reference		5 (55.6)	4 (44.4)	Reference
2	16 (100)	0 (0)	0.78 (0.01-73.61)	0.916	12 (75)	4 (25)	1.45 (0.28-7.51)	0.659
3	20 (80)	5 (20)	6.16 (0.21-178)	0.290	20 (80)	5 (20)	1.62 (0.31-8.37)	0.567
4	7 (87.5)	1 (12.5)	5.16 (0.12-215)	0.389	4 (50)	4 (50)	4.64 (0.84-25.69)	0.079
Retrieved LN, n (%)				1.000				0.477
< 12	10 (90.9)	1 (11.1)	Reference		8 (72.7)	3 (27.3)	Reference
≥ 12	38 (86.4)	6 (13.6)			31 (70.5)	13 (29.5)	1.56 (0.46-5.32)
Missing	3	-
LN Ratio, mean ± SD)	24 ± 17	27 ± 29	12.13 (0.84-174)	0.066	29 ± 20	15 ± 16	0.64 (0.04-11.17)	0.757
Colloid component, n (%)				0.106				0.396
No	13 (100)	0 (0)	Reference		9 (69.2)	4 (30.8)	Reference
Yes	10 (66.7)	5 (33.3)	13.77 (0.57-330)		9 (60)	6 (40)	1.77 (0.47-6.62)
Missing	28	2			23	7

¹According to the tumor node metastasis staging system.

HR: Hazard ratio; CI: Confidential intervals; AJCC: American Joint Committee on Cancer; LN: Lymph node.