The Prognostic Significance of Postoperative Adjuvant Chemotherapy in the Population Aged 75 Years and Older with Stage II–III Colorectal Cancer: A Retrospective Multi-Center Cohort Study

Figures & data

Figure 1 Consort Diagram of the Study Population.

Notes: Schulz KF, Altman DG, Moher D, CONSORT 2010 Statement: Updated Guidelines for Reporting Parallel Group Randomised Trials. PLoS Med. 2010;7(3): e1000251. Copyright: © 2010 Schulz et al. Creative Commons Attribution License.¹⁹

Table 1 Patient and Tumor Characteristics

Characteristics	All^a (N=2885)	No Chemotherapy^a (N=753)	Chemotherapy^a (N=2132)	P-value^b
Gender, no. (%) of patients				0.003
Male	1729 (59.9%)	417 (55.4%)	1312 (61.5%)
Female	1156 (40.1%)	336 (44.6%)	820 (38.5%)
Age, years				<0.001
Median (IQR)	60 (50, 67)	64 (55, 71)	58 (49, 65)
Mean (SD)	58.42 (12.01)	63.08 (11.49)	56.78 (11.75)
BMI				0.01
Median (IQR)	22.4 (20.7, 24.8)	22.2 (20.5, 24.4)	22.5 (20.8, 25.0)
Mean (SD)	22.70 (3.23)	22.42 (3.27)	22.82 (3.21)
Surgical approach				0.05
OR	1549 (53.7%)	428 (56.8%)	1121 (52.6%)
LR	1336 (46.3%)	325 (43.2%)	1011 (47.4%)
Primary site, no. (%) of patients				<0.001
Colon	1645 (57.0%)	341 (45.3%)	1304 (61.2%)
Rectum	1240 (43.0%)	412 (54.7%)	828 (38.8%)
Tumor differentiation, no. (%) of patients				0.05
Well	123 (4.3%)	30 (4.0%)	93 (4.4%)
Moderate	110 (3.8%)	27 (3.6%)	83 (3.9%)
Poor-undifferentiated	1860 (64.5%)	503 (66.8%)	1357 (63.6%)
Unknown	792 (27.5%)	193 (25.6%)	599 (28.1%)
Mucinous type				<0.001
No	2169 (75.2%)	632 (83.9%)	1537 (72.1%)
Yes	667 (23.1%)	115 (15.3%)	552 (25.9%)
Unknown	49 (1.7%)	6 (0.8%)	43 (2.0%)
T stage, no. (%) of patients				0.10
T1-T2	139 (4.8%)	32 (4.2%)	107 (5.0%)
T3	2523 (87.5%)	675 (89.6%)	1848 (86.7%)
T4	223 (7.7%)	46 (6.1%)	177 (8.3%)
N stage, no. (%) of patients				<0.001
N0	1421 (49.3%)	482 (64%)	939 (44.0%)
N1	1017 (35.3%)	196 (26%)	821 (38.5%)
N2	447 (15.5%)	75 (10.0%)	372 (17.4%)
AJCC 8th ed. stage				<0.001
II	1420 (49.2%)	481 (63.9%)	939 (44.0%)
III	1465 (50.8%)	272 (36.1%)	1193 (56.0%)
Lymph node yield				0.89
≥12	2368 (83.8%)	593 (84.0%)	1775 (83.7%)
<12	459 (16.2%)	113 (16.0%)	346 (16.3%)
LVI				0.02
No	2568 (89.0%)	689 (91.5%)	1879 (88.2%)
Yes	316 (11.0%)	64 (8.5%)	252 (11.8%)
PNI				<0.001
No	2682 (93.3%)	729 (97.1%)	1953 (91.9%)
Yes	193 (6.7%)	22 (2.9%)	171 (8.1%)
Tumor deposit				0.003
No	1960 (89.3%)	600 (92.4%)	1360 (88.0%)
Yes	235 (10.7%)	49 (7.6%)	186 (12.0%)
Preoperative CEA, ng/mL				0.04
Median (IQR)	4 (2, 10)	4 (2, 11)	4 (2, 10)
Mean (SD)	15.45 (100.26)	22.07 (188.79)	13.12 (32.88)
Postoperative CEA, ng/mL				0.26
Median (IQR)	2.00 (1.24, 3.07)	2.07 (1.32, 3.49)	1.98 (1.23, 3.00)
Mean (SD)	8.83 (95.32)	12.82 (127.21)	7.72 (84.35)
Age group				<0.001
≤40	215 (7.5%)	26 (3.5%)	189 (8.9%)
41–74	2446 (84.8%)	604 (80.2%)	1842 (86.4%)
≥75	224 (7.8%)	123 (16.3%)	101 (4.7%)

Notes: ^aData are median (IQR), Mean (SD) or n (%). ^bP value, using Pearson’s Chi-squared test; Wilcoxon rank sum test; Fisher’s exact test. Bold text in the table indicates P≤ 0.05.

Abbreviations: BMI, Body Mass Index; CEA, carcinoembryonic antigen; LR, laparoscopic resection; LVI, lymphovascular invasion; OR, open resection; PNI, perineural invasion; AJCC, American Joint Committee on Cancer.

Table 2 Univariate and Multivariate Analyses of Overall Cohort

Variable	Univariate HR (95% CI)	P-value	Multivariate HR (95% CI)	P-value
Sex
Male	1.0 (Reference)		1.0 (Reference)
Female	1.08 (0.89–1.32)	0.42	1.06 (0.84–1.35)	0.63
Age group
≤40	1.0 (Reference)		1.0 (Reference)
41–74	0.92 (0.64–1.32)	0.65	0.82 (0.54–1.23)	0.33
≥75	1.27 (0.80–2.01)	0.31	1.05 (0.61–1.81)	0.85
BMI group
<24	1.0 (Reference)		1.0 (Reference)
≥24`	0.79 (0.62–1.00)	0.05	0.76 (0.59–0.99)	0.04
Surgical approach`
OR	1.0 (Reference)		1.0 (Reference)
LR	0.47 (0.38–0.58)	<0.001	0.53 (0.4–0.71)	<0.001
Tumor location`
Colon	1.0 (Reference)		1.0 (Reference)
Rectum	1.43 (1.17–1.73)	<0.001	1.1 (0.86–1.4)	0.45
Tumor differentiation
Well-Morederate	1.0 (Reference)		1.0 (Reference)
Poor-undifferentiated	0.78 (0.54–1.11)	0.17	0.53 (0.33–0.86)	0.01
Unknown	1.44 (1.00–2.07)	0.05	0.66 (0.41–1.08)	0.1
Mucinous type`
No	1.0 (Reference)		1.0 (Reference)
Yes	0.54 (0.41–0.72)	<0.001	0.74 (0.43–1.26)	0.26
Pathology T stage`
T1-T3	1.0 (Reference)		1.0 (Reference)
T4	1.29 (0.92–1.8)	0.14	1.02 (0.61–1.7)	0.94
Pathology N stage`
N0	1.0 (Reference)		1.0 (Reference)
N1	2.09 (1.64–2.67)	<0.001	2.22 (1.64–3.01)	<0.001
N2	4.76 (3.71–6.11)	<0.001	4.07 (2.93–5.66)	<0.001
Lymph node yield`
≥12	1.0 (Reference)		1.0 (Reference)
<12	1.19 (0.93–1.53)	0.17	1.05 (0.78–1.43)	0.73
LVI
No	1.0 (Reference)		1.0 (Reference)
Yes	2.32 (1.83–2.95)	<0.001	1.66 (1.17–2.35)	<0.001
PNI
No	1.0 (Reference)		1.0 (Reference)
Yes	1.81 (1.33–2.48)	<0.001	2.01 (1.2–3.37)	0.01
Tumor deposit
No	1.0 (Reference)		1.0 (Reference)
Yes	2.32 (1.76–3.06)	<0.001	1.37 (0.99–1.9)	0.06
Adjuvant chemotherapy
No	1.0 (Reference)		1.0 (Reference)
Yes	0.72 (0.58–0.88)	<0.001	0.77 (0.58–1.01)	0.06
Preoperative CEA group
≤5	1.0 (Reference)		1.0 (Reference)
>5	1.85 (1.52–2.25)	<0.001	1.44 (1.13–1.85)	<0.001
Postoperative CEA group
≤5	1.0 (Reference)		1.0 (Reference)
>5	3 (2.33–3.86)	<0.001	2.56 (1.92–3.42)	<0.001

Notes: Bold text in the table indicates P < 0.001.

Abbreviations: BMI, Body Mass Index; CEA, carcinoembryonic antigen; LR, laparoscopic resection; LVI, lymphovascular invasion; OR, open resection; PNI, perineural invasion; AJCC, American Joint Committee on Cancer.

Figure 2 Kaplan-Meier curves for recurrence-free survival that Associated with the Use of Adjuvant Chemotherapy in Overall cohort (a), young group (b), middle-aged group (c), pre-matched senior group (d) post-matched senior group (e).

Table 3 Characteristics of Patients 75 Years and Older Who Underwent Surgery for Colorectal Cancer Before and After Matching

Characteristic	Before Propensity-Matched				After Propensity-Matched
	Overall	No	Chemotherapy (N = 70)^a	P-value^b	Overall	No	Chemotherapy, (N = 42)^a	P-value^b
	(N = 151)^a	Chemotherapy (N = 81)^a			(N = 84)^a	Chemotherapy (N = 42)^a
Sex (%)				0.06				0.48
Male	97 (64.2)	46 (56.8)	51 (72.9)		58 (69.0)	27 (64.3)	31 (73.8)
Female	54 (35.8)	35 (43.2)	19 (27.1)		26 (31.0)	15 (35.7)	11 (26.2)
Age				0.001				0.36
Mean (SD)	77.96 (2.96)	78.73 (3.43)	77.07 (2.00)		77.40 (2.12)	77.19 (2.12)	77.62 (2.12)
Mean (IQR)	77.00 (76.00, 79.00)	79.00 (76.00, 80.00)	76.00 (76.00, 78.00)		77.0 (76.00, 79.00)	76.5 (75.0, 79.0)	77 (76.0, 79.0)
BMI				0.98				0.72
Mean (SD)	22.11 (2.94)	22.10 (3.00)	22.11 (2.89)		22.09 (2.85)	22.20 (2.85)	21.98 (2.87)
Mean (IQR)	21.83 (20.31, 24.13)	21.55 (20.76, 24.22)	22.66 (20.20, 23.98)		21.32 (20.28, 24.08)	21.32 (20.76, 24.39)	21.34 (19.91, 23.98)
Surgical approach (%)				0.73				0.51
OR	96 (63.6)	53 (65.4)	43 (61.4)		50 (59.5)	27 (64.3)	23 (54.8)
LR	55 (36.4)	28 (34.6)	27 (38.6)		34 (40.5)	15 (35.7)	19 (45.2)
Tumor location (%)				0.45				0.66
Colon	78 (51.7)	39 (48.1)	39 (55.7)		47 (56.0)	22 (52.4)	25 (59.5)
Rectum	73 (48.3)	42 (51.9)	31 (44.3)		37 (44.0)	20 (47.6)	17 (40.5)
Tumor differentiation (%)				0.12				0.11
Well	5 (3.3)	1 (1.2)	4 (5.7)		3 (3.6)	0 (0.0)	3 (7.1)
Moderate	98 (64.9)	57 (70.4)	41 (58.6)		53 (63.1)	30 (71.4)	23 (54.8)
Poor-undifferentiated	48 (31.8)	23 (28.4)	25 (35.7)		28 (33.3)	12 (28.6)	16 (38.1)
Unknown	5 (3.3)	1 (1.2)	4 (5.7)		3 (3.6)	0 (0.0)	3 (7.1)
Mucinous type (%)				0.3				>0.99
No	143 (94.7)	75 (92.6)	68 (97.1)		81 (96.4)	40 (95.2)	41 (97.6)
Yes	8 (5.3)	6 (7.4)	2 (2.9)		3 (3.6)	2 (4.8)	1 (2.4)
Pathology T stage (%)				0.64				>0.99
T1–3	142 (94.0)	75 (92.6)	67 (95.7)		81 (96.4)	41 (97.6)	40 (95.2)
T4	9 (6.0)	6 (7.4)	3 (4.3)		3 (3.6)	1 (2.4)	2 (4.8)
Pathology N stage (%)				0.19				0.32
N0	89 (58.9)	52 (64.2)	37 (52.9)		50 (59.5)	26 (61.9)	24 (57.1)
N1	47 (31.1)	20 (24.7)	27 (38.6)		27 (32.1)	11 (26.2)	16 (38.1)
N2	15 (9.9)	9 (11.1)	6 (8.6)		7 (8.3)	5 (11.9)	2 (4.8)
AJCC 7th ed. Stage (%)				0.21				0.82
II	89 (58.9)	52 (64.2)	37 (52.9)		50 (59.5)	26 (61.9)	24 (57.1)
III	62 (41.1)	29 (35.8)	33 (47.1)		34 (40.5)	16 (38.1)	18 (42.9)
Lymph node yield (%)				0.39				0.38
≥12	120 (79.5)	67 (82.7)	53 (75.7)		70 (83.3)	33 (78.6)	37 (88.1)
<12	31 (20.5)	14 (17.3)	17 (24.3)		14 (16.7)	9 (21.4)	5 (11.9)
LVI (%)				>0.99				>0.99
No	137 (90.7)	74 (91.4)	63 (90.0)		79 (94.0)	40 (95.2)	39 (92.9)
Yes	14 (9.3)	7 (8.6)	7 (10.0)		5 (6.0)	2 (4.8)	3 (7.1)
PNI (%)				0.94				>0.99
No	150 (99.3)	81 (100.0)	69 (98.6)		84 (100.0)	42 (100.0)	42 (100.0)
Yes	1 (0.7)	0 (0.0)	1 (1.4)		0 (0.0)	0 (0.0)	0 (0.0)
Tumor deposit (%)				0.28				0.20
No	131 (86.8)	73 (90.1)	58 (82.9)		73 (86.9)	39 (92.9)	34 (81.0)
Yes	20 (13.2)	8 (9.9)	12 (17.1)		11 (13.1)	3 (7.1)	8 (19.0)
Preoperative CEA				0.13				0.70
Mean (SD)	15.85 (32.35)	10.46 (14.43)	22.09 (44.26)		15.65 (35.06)	11.14 (15.02)	20.16 (47.13)
Mean (IQR)	5 (3, 12)	5 (3, 10)	6 (3, 15)		5 (3, 13)	5 (2, 12)	5 (3, 12)
Postoperative CEA				0.02				0.30
Mean (SD)	7.53 (37.74)	6.08 (24.61)	9.22 (48.88)		6.06 (24.19)	9.36 (34.01)	2.76 (2.34)
Mean (IQR)	2.26 (1.30, 3.71)	1.87 (1.22, 3.21)	2.59 (1.78, 4.23)		2.13 (1.13, 3.00)	1.73 (1.02, 3.11)	2.20 (1.29, 2.96)
Preoperative CEA group (%)				0.09				0.66
≥5	75 (49.7)	46 (56.8)	29 (41.4)		43 (51.2)	23 (54.8)	20 (47.6)
<5	76 (50.3)	35 (43.2)	41 (58.6)		41 (48.8)	19 (45.2)	22 (52.4)
Postoperative CEA group (%)				0.05				>0.99
≥5	129 (85.4)	74 (91.4)	55 (78.6)		76 (90.5)	38 (90.5)	38 (90.5)
<5	22 (14.6)	7 (8.6)	15 (21.4)		8 (9.5)	4 (9.5)	4 (9.5)
Death (%)				0.52				>0.99
No	121 (80.1)	67 (82.7)	54 (77.1)		72 (85.7)	36 (85.7)	36 (85.7)
Yes	30 (19.9)	14 (17.3)	16 (22.9)		12 (14.3)	6 (14.3)	6 (14.3)
Recurrence (%)				0.40				0.74
No	124 (82.1)	69 (85.2)	55 (78.6)		74 (88.1)	38 (90.5)	36 (85.7)
Yes	27 (17.9)	12 (14.8)	15 (21.4)		10 (11.9)	4 (9.5)	6 (14.3)

Notes: ^aData are median (IQR), Mean (SD) or n (%). ^bP value, using Pearson’s Chi-squared test; Wilcoxon rank sum test; Fisher’s exact test. Bold text in the table indicates P≤0.05.

Abbreviations: BMI, Body Mass Index; CEA, carcinoembryonic antigen; LR, laparoscopic resection; LVI, lymphovascular invasion; OR, open resection; PNI, perineural invasion.

Schulz KF, Altman DG, Moher D. CONSORT Statement: Updated Guidelines for Reporting Parallel Group Randomised Trials. PLoS Med. 2010;7(3):e1000251.

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