The clinical value of C-reactive protein and its association with tumour location in patients undergoing curative surgery for colorectal cancer – a ScotScan collaborative study

Figures & data

Table 1. Clinicopathological characteristics and associations to CRP values.

	Characteristic			CRP values
			n = 2059 (%)	<10	11–30	31–60	61–100	>100	p-value (χ^2)
SIR	CRP (mg/l)	Median(min–max)	6.0 (0.5–429)						N/A
				1368 (66.4)	374 (18.2)	172 (8.3)	78 (3.8)	67 (3.2)
	Albumin (g/l)	>35	1642 (79.7)	1225 (89.5)	261 (69.8)	98 (57.0)	33 (42.3)	25 (37.3)	<0.001
		<35	417 (20.2)	143 (10.4)	113 (30.2)	74 (43.0)	45 (57.7)	42 (62.7)
	mGPS	0	1368 (66.5)	1368 (100.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	<0.001
		1	417 (20.2)	0 (0.0)	261 (69.8)	98 (57.0)	33 (42.3)	25 (37.3)
		2	274 (13.3)	0 (0.0)	113 (30.2)	74 (43.0)	45 (57.7)	42 (62.7)
Demography	Age. years	<65	551 (26.7)	377 (27.5)	91 (24.3)	37 (21.5)	24 (30.8)	22 (32.8)	0.034
		65–74	673 (32.7)	471 (34.4)	110 (29.4)	50 (29.1)	23 (29.5)	19 (28.4)
		>75	835 (40.6)	520 (38.0)	173 (46.3)	85 (49.4)	31 (39.7)	26 (38.8)
	Sex	Female	1014 (49.2)	642 (46.9)	196 (52.4)	103 (59.9)	39 (50.0)	34 (50.7)	0.015
		Male	1045 (50.7)	726 (53.1)	178 (47.6)	69 (40.1)	39 (50.0)	33 (49.3)
Clinical Pathology	Year of surgery	1997–2005	485 (23.6)	264 (19.3)	118 (31.6)	46 (26.7)	26 (33.3)	31 (46.3)	<0.001
		2006–2010	460 (22.3)	290 (21.2)	86 (23.0)	47 (27.3)	21 (26.9)	16 (23.9)
		2011–2013	483 (23.4)	351 (25.6)	79 (21.1)	33 (19.2)	13 (16.7)	7 (10.4)
		2014–2017	631 (30.6)	463 (33.8)	91 (24.3)	46 (26.7)	18 (23.1)	13 (19.4)
	Presentation	Elective	1852 (90.0)	1306 (95.5)	333 (89.0)	139 (80.8)	49 (62.8)	25 (37.3)	<0.001
		Emergency	206 (10.0)	61 (4.5)	41 (11.0)	33 (19.2)	29 (37.2)	42 (62.7)
	ASA score	I	188 (11.1)	148 (13.0)	20 (6.8)	12 (8.4)	5 (8.1)	3 (5.1)	0.007
		II	684 (40.3)	473 (41.5)	118 (40.3)	56 (39.2)	18 (29.0)	19 (32.2)
		III	745 (44.0)	472 (41.4)	138 (47.1)	69 (48.2)	35 (56.4)	31 (52.5)
		IV	79 (4.6)	46 (4.0)	17 (5.8)	6 (4.2)	4 (6.5)	6 (10.2)
	Adjuvant therapy	No	1588 (78.6)	1071 (80.0)	280 (75.9)	132 (77.6)	58 (77.3)	47 (71.2)	0.243
		Yes	431 (21.3)	268 (20.0)	89 (24.1)	38 (22.4)	17 (22.7)	19 (28.8)
	Tumour location	Right	907 (44.2)	539 (39.5)	191 (51.2)	98 (57.3)	47 (60.2)	32 (47.8)	<0.001
		Left	702 (34.2)	470 (34.4)	124 (33.2)	55 (32.2)	25 (32.0)	28 (41.8)
		Rectum	444 (21.6)	355 (26.0)	58 (15.5)	18 (10.5)	6 (7.7)	7 (10.4)
	T-stage	1	178 (8.6)	159 (11.6)	12 (3.2)	5 (2.9)	2 (2.6)	0 (0.0)	<0.001
		2	305 (14.8)	265 (19.4)	32 (8.5)	6 (3.5)	1 (1.3)	1 (1.5)
		3	1231(59.8)	795 (58.1)	240 (64.2)	117 (68.0)	40 (51.3)	39 (58.2)
		4	345 (16.7)	149 (10.9)	90 (24.1)	44 (25.6)	35 (44.9)	27 (40.3)
	N-stage	0	1325 (64.3)	906 (66.2)	223 (59.6)	110 (64.0)	47 (60.3)	39 (58.2)	0.024
		1	535 (26.0)	354 (25.9)	100 (26.7)	43 (25.0)	21 (26.9)	17 (25.4)
		2	199 (9.7)	108 (7.9)	51 (13.6)	19 (11.0)	10 (12.8)	11 (16.4)
	TNM-stage	I	412 (20.0)	362 (26.5)	38 (10.2)	9 (5.2)	2 (2.6)	1 (1.5)	<0.001
		II	913 (44.3)	544 (39.8)	185 (49.5)	101 (58.7)	45 (57.7)	38 (56.7)
		III	734 (35.6)	462 (33.8)	151 (40.4)	62 (36.0)	31 (39.7)	28 (41.8)
	Differentiation	Well/moderate	1745 (87.5)	1211 (91.5)	300 (83.1)	129 (77.7)	55 (72.4)	50 (75.8)	<0.001
		Poor	248 (12.4)	113 (8.5)	61 (16.9)	37 (22.3)	21 (27.6)	16 (24.2)

SIR: systemic inflammatory response; CRP: C-reactive protein; mGPS: modified Glasgow Prognostic Score; ASA: American Society of Anaesthesiologists; Min: minimum; Max: maximum

Table 2. Prognostic information regarding overall and cancer-specific survival for patients undergoing surgery for colorectal cancer stage I–III according to CRP and mGPS.

CRC stage I–III (n = 2059)
		OS (Events = 594)				CSS (Events = 318)
	n	HR	CI		p-value	HR	CI		p-value
CRP					<0.001				<0.001
<10	1368	1.00				1.00
11–30	374	1.65	1.35	2.02	<0.001	1.85	1.41	2.44	<0.001
31–60	172	1.95	1.50	2.52	<0.001	2.30	1.63	3.25	<0.001
60–100	78	2.37	1.68	3.34	<0.001	3.43	2.27	5.20	<0.001
>100	67	2.69	1.89	3.83	<0.001	3.02	1.88	4.87	<0.001
mGPS					<0.001				<0.001
0	1368	1.00				1.00
1	417	1.47	1.20	1.79	0.001	1.67	1.27	2.20	0.002
2	274	2.63	2.16	3.21	<0.001	3.22	2.47	4.19	<0.001

CRP: C-reactive protein (mg/l); mGPS: modified Glasgow Prognostic Score; OS: overall survival; CSS: cancer-specific survival; HR: hazard ratio; CI: confidence interval (95%)

Table 3. Relationship between clinicopathological characteristics and tumour sidedness with left side as reference, including rectum.

		Univariate (n = 2053)				Multivariate (n = 1629)
Characteristic		OR	CI		p-value	OR	CI		p-value
Age. years (<65/65–74/>75)		1.30	1.16	1.45	<0.001	1.25	1.10	1.42	<0.001
Sex (female/male)		0.72	0.60	0.85	<0.001	0.85	0.69	1.04	0.120
ASA score (I/II/III/IV)		1.29	1.13	1.47	<0.001	1.08	0.92	1.25	0.343
Year of surg. quartile		1.17	1.08	1.26	<0.001	1.15	1.05	1.25	0.002
Adjuvant therapy (no/yes)		0.94	0.76	1.17	0.592	–
TNM-stage (I/II/III)		1.14	1.01	1.29	0.030	1.00	0.87	1.16	0.993
Differentiation (moderate-well/poor)		3.92	2.93	5.27	<0.001	3.67	2.64	5.11	<0.001
CRP. mg/l < 10	n = 1368				<0.001				<0.001
11−30	n = 374	1.61	1.28	2.02	<0.001	1.64	1.25	2.16	<0.001
31−60	n = 172	2.05	1.49	2.83	<0.001	1.67	1.15	2.43	0.007
61−100	n = 78	2.32	1.46	3.70	<0.001	1.88	1.07	3.28	0.027
>100	n = 67	1.40	0.86	2.29	0.180	1.33	0.76	2.33	0.313

CRP: C-reactive protein (mg/l); ASA: American Society of Anaesthesiologists; OR: odds ratio; CI: confidence interval (95%).

Table 4. Relationship between clinicopathological factors and cancer-specific survival according to primary tumour location.

Right side		Univariate (n = 907/events = 142)				Multivariate (n = 755/events = 108)
Characteristic		HR	CI		p-value	HR	CI		p-value
Age. years (<65/65–74/>75)		1.58	1.26	1.99	<0.001	1.58	1.19	2.10	0.002
Sex (female/male)		1.01	0.73	1.41	0.932	–
ASA score (I/II/III/IV)		1.63	1.24	2.15	<0.001	1.33	0.98	1.79	0.065
Year of surg. quartile		0.67	0.57	0.77	<0.001	0.73	0.61	0.86	<0.001
Adjuvant therapy (no/yes)		1.12	0.76	1.65	0.556	–
TNM-stage (I/II/III)		2.62	1.97	3.48	<0.001	2.31	1.66	3.21	<0.001
Differentiation (moderate-well/poor)		1.27	0.86	1.87	0.233	–
CRP. mg/l < 10	n = 539				<0.001				0.059
11–30	n = 191	1.53	1.01	2.33	0.047	0.97	0.59	1.59	0.912
31–60	n = 98	1.95	1.19	3.19	0.008	1.40	0.78	2.49	0.258
61–100	n = 47	2.62	1.44	4.75	0.002	1.61	0.76	3.42	0.213
>100	n = 32	3.57	1.88	6.77	<0.001	2.73	1.31	5.72	0.008
Left side (excluding rectum)		Univariate (n = 702/events = 103)				Multivariate (n = 582/events = 76)
Characteristic		HR	CI		p-value	HR	CI		p-value
Age. years (<65/65–74/>75)		1.46	1.13	1.87	0.003	1.34	0.98	1.83	0.067
Sex (female/male)		0.98	0.67	1.45	0.937	–
ASA score (I/II/III/IV)		2.33	1.67	3.27	<0.001	1.92	1.34	2.75	<0.001
Year of surg. quartile		0.74	0.62	0.88	<0.001	0.88	0.72	1.07	0.200
Adjuvant (no/yes)		1.01	0.65	1.57	0.961	–
TNM-stage (I/II/III)		2.74	1.97	3.81	<0.001	3.44	2.21	5.36	<0.001
Differentiation (moderate-well/poor)		1.54	0.75	3.16	0.243	–
CRP. mg/l < 10	n = 470				<0.001				<0.001
11–30	n = 124	3.03	1.88	4.89	<0.001	2.44	1.37	4.36	0.003
31–60	n = 55	3.99	2.23	7.13	<0.001	3.85	2.02	7.36	<0.001
61–100	n = 25	6.36	3.26	1.40	<0.001	4.47	2.02	9.86	<0.001
>100	n = 28	3.64	1.63	8.13	0.002	3.53	1.46	8.54	0.005
Rectum		Univariate (n = 444/events = 71)				Multivariate (n = 334/events = 53)
Characteristic		HR	CI		p-value	HR	CI		p-value
Age. years (<65/65–74/>75)		1.18	0.89	1.58	0.244	–
Sex (female/male)		1.25	0.78	2.03	0.353	–
ASA score (I/II/III/IV)		1.47	1.03	2.11	0.035	1.56	1.07	2.26	0.020
Year of surg. quartile		0.62	0.50	0.78	<0.001	0.68	0.53	0.88	0.003
Adjuvant (no/yes)		1.76	1.03	3.16	0.038	0.88	0.44	1.75	0.708
TNM-stage (I/II/III)		2.30	1.64	3.22	<0.001	1.70	1.14	2.53	0.009
Differentiation (moderate-well/poor)		4.71	2.62	8.48	<0.001	3.61	1.81	7.22	<0.001
CRP. mg/l < 10	n = 355				0.276
11–30	n = 58	1.58	0.84	2.95	0.156	–
31–60	n = 18	1.67	0.60	4.60	0.326	–
61–100	n = 6	3.41	0.83	14.03	0.089	–
>100	n = 7	1.12	0.15	8.11	0.910	–

CRP: C-reactive protein (mg/l); ASA: American Society of Anaesthesiologists; HR: hazard ratio; CI: confidence interval (95%).

Figure 1. (a–d) Relationship between C-reactive protein (CRP) values (in mg/l) and survival for patients undergoing curative treatment for colorectal cancer (CRC) according to tumour sidedness, with all patients shown in black, right side shown in red and left side (excluding rectum) shown in blue. The number of patients at each CRP level is noted as n below the respected level. All HRs are adjusted to clinicopathological factors (age, sex, ASA score, year of surgery, TNM-stage, and differentiation). All HR-, CI-, and p-values are shown in Supplementary Table 3(a–d). Clinicopathological characteristics of the patient cohort when excluding emergency surgery and postoperative mortality are shown in Supplementary Table 1. (a) The relationship between CRP level and OS according to tumour location. (b) The relationship between CRP level and CSS according to tumour location. (c) The relationship between CRP level and OS according to tumour location excluding patients undergoing emergency surgery (n = 206) and postoperative death (within 30 days of surgery, n = 40). (d) The relationship between CRP level and CSS according to tumour location excluding patients undergoing emergency surgery and postoperative death.

Data availability statement

Anonymised data for this study are available from the corresponding author on reasonable request.