Temporal development in survival, and gender and regional differences in the Swedish population of patients with synchronous and metachronous metastatic colorectal cancer

Figures & data

Table 1. Background demographics for time periods (2007–2011 vs 2012–2016) and further divided by presentation of metastases.

		All					Synchronous					Metachronous
		2007–2011		2012–2016		p Value	2007–2011		2012–2016		p Value	2007–2011		2012–2016		p Value
		N = 8755, 45 %		N = 10728, 55 %			N = 6352, 33 %		N = 7278, 37 %			N = 2403, 12%		N = 3450, 18 %
Median age	(range)	71 (20–100)		72 (18–102)		<0.001	71 (20–100)		71 (19–102)		<0.001	73 (26–98)		73 (18–97)		0.140
Age groups	18–59	1523	17 %	1710	16 %	0.007	1190	19 %	1260	17 %	0.080	333	14 %	450	13 %	0.433
	60–69	2400	27 %	2851	27 %		1772	28 %	1995	27 %		628	26 %	856	25 %
	70–79	2830	32 %	3586	33 %		1987	31 %	2329	32 %		843	35 %	1257	36 %
	≥80	2002	23 %	2581	24 %		1403	22 %	1694	23 %		599	25 %	887	26 %
Sex	Female	4030	46 %	4781	45 %	0.041	2881	45 %	3277	45 %	0.700	1149	48 %	1504	44 %	0.001
	Male	4725	54 %	5947	55 %		3471	55 %	4001	55 %		1254	52 %	1946	56 %
Primary location	Appendix	97	1 %	131	1 %	–	73	1 %	98	1 %	–	24	1 %	33	1 %	–
	Right colon	2955	34 %	3708	35 %	0.211	2130	34 %	2555	35 %	0.052	825	34 %	1153	33 %	0.738
	Left colon	2705	31 %	3194	30 %		2008	32 %	2172	30 %		697	29 %	1022	30 %
	Rectum	2940	34 %	3640	34 %		2087	33 %	2400	33 %		853	35 %	1240	36 %
	Unknown/multiple	58	1 %	55	1 %	–	54	1 %	53	1 %	–	4	0 %	2	0 %	–
Primary resection	Not resected	2324	27 %	3626	34 %	<0.001	2324	37 %	3626	50 %	<0.001	0	0 %	0	0 %	NE
	Open and close	784	9 %	656	6 %		784	12 %	656	9 %		0	0 %	0	0 %
	Resected	5647	65 %	6446	60 %		3244	51 %	2996	41 %		2403	100 %	3450	100 %
Degree of	Well/moderate	4380	71 %	4238	72 %	0.217	2710	70 %	1826	68 %	0.270	1670	74 %	2412	75 %	0.208
differentiation	Poor/undifferentiated	1771	29 %	1630	28 %		1184	30 %	847	32 %		587	26 %	783	25 %
	Missing	2604	–	4860	–	–	2458	–	4605	–	–	146	–	255	–	–
Presentation	Synchronous	6352	73 %	7278	68 %	<0.001	6352	100 %	7278	100 %	NE	0	0 %	0	0 %	NE
of metastases	Metachronous	2403	27 %	3450	32 %		0	0 %	0	0 %		2403	100 %	3450	100 %
Number of	1	5243	60 %	6415	60 %	<0.001	3663	58 %	4218	58 %	<0.001	1580	66 %	2197	64 %	0.019
metastatic sites	2	2613	30 %	2915	27 %		2007	32 %	2066	29 %		606	25 %	849	25 %
	≥3	858	10 %	1325	12 %		645	10 %	943	13 %		213	9 %	382	11 %
	Missing	41	–	73	–	–	37	–	51	–	–	4	–	22	–	–
Metastatic sites	Liver	6186	71 %	6833	64 %	<0.001	4910	77 %	5173	71 %	<0.001	1276	53 %	1660	48 %	<0.001
	Lung	3330	38 %	4236	40 %	0.039	2357	37 %	2728	38 %	0.650	973	41 %	1508	44 %	0.014
	Other	2779	32 %	3675	34 %	<0.001	1945	31 %	2414	33 %	0.001	834	35 %	1261	37 %	0.148
	Local only	322	4 %	716	7 %	<0.001	79	1 %	370	5 %	<0.001	243	10 %	346	10 %	0.917
	Lateral/inguinal nodes only	31	0 %	75	1 %	0.001	31	1 %	75	1 %	<0.001	0	0 %	0	0 %	NE
Healthcare region	1	1656	19 %	2012	19 %	0.004	1234	19 %	1298	17 %	0.019	422	18 %	714	21 %	<0.001
	2	1909	22 %	2594	24 %		1399	22 %	1743	23 %		510	21 %	851	25 %
	3	990	11 %	1187	11 %		724	11 %	772	10 %		266	11 %	415	12 %
	4	1656	19 %	1976	18 %		1186	19 %	1351	18 %		470	20 %	625	18 %
	5	1756	20 %	2040	19 %		1240	20 %	1474	19 %		516	21 %	566	16 %
	6	787	9 %	903	8 %		569	9 %	625	8 %		218	9 %	278	8 %
	Missing	1	–	16	–	–	0	–	15	–	–	1	–	1	–	–

NE: no estimate.

Figure 1. Overall survival between patients diagnosed 2007–2011 and 2012–2016 for all patients (A), synchronous presentation (B), metachronous (excluding local recurrence only) (C), and local recurrence only (D).

Figure 2. Overall survival by sex (A and B), primary location (C and D), and healthcare region (E and F) in the two time periods (2007–2011 [left panes] vs 2012–2016 [right panes]).

Table 2. Median overall survival and 5-year overall survival rates divided in time periods (2012–2016 vs. 2007–2011) in subgroups of age, sex, primary location, degree of differentiation, presentation of metastases, metastatic sites and healthcare region.

		Median OS (months)			Comparison of OS^a			5-year OS rate
		All	2007–2011	2012–2016	HR	95% CI	p Value	2007–2011	2012–2016	p Value
		(95% CI)	(95% CI)	(95% CI)				(95% CI)	(95% CI)
All		14.0 (13.7–14.4)	13.1 (12.7–13.6)	14.9 (14.4–15.3)	0.89	0.86–0.92	<0.001	13% (12.8–14.2)	16% (15.5–17.3)	<0.001
Age groups	18–59	22.3 (21.1–23.4)	20.9 (19.4–22.4)	23.6 (21.8–25.4)	0.89	0.82–0.97	0.005	21% (18.9–23.0)	25% (22.6–27.9)	0.011
	60–69	20.0 (19.1–20.8)	18.8 (17.7–19.9)	21.2 (20.0–22.4)	0.90	0.85–0.96	0.002	19% (17.1–20.2)	22% (19.6–23.5)	0.025
	70–79	13.3 (12.8–13–9)	11.8 (11.1–12.6)	14.5 (13.7–15.3)	0.84	0.80–0.89	<0.001	11% (10.2–12.6)	16% (14.0–17.0)	<0.001
	≥80	6.5 (6.2–6.9)	5.8 (5.3–6.3)	7.2 (6.6–7.7)	0.87	0.82–0.93	<0.001	5% (3.7–5.5)	5% (4.2–6.7)	0.263
Sex	Male	15.0 (14.6–15.5)	13.9 (13.3–14.5)	16.2 (15.5–16.9)	0.88	0.85–0.92	<0.001	13% (12.5–14.4)	17% (15.5–18.0)	<0.001
	Female	12.8 (12.3–13.3)	11.9 (11.2–12.6)	13.3 (12.7–14.0)	0.91	0.86–0.95	<0.001	14% (12.5–14.6)	16% (14.6–17.2)	0.006
Primary location^b	Right colon	9.4 (9.0–9.9)	8.8 (8.1–9.4)	9.8 (9.2–10.4)	0.90	0.86–0.95	<0.001	9% (8.3–10.4)	12% (11.0–13.6)	<0.001
	Left colon	16.5 (15.7–17.2)	15.4 (14.5–16.3)	17.6 (16.5–18.7)	0.91	0.86–0.97	0.002	16% (15.1–17.9)	18% (16.5–20.0)	0.129
	Rectum	17.9 (17.2–18.6)	16.0 (15.1–17.0)	19.2 (18.1–20.3)	0.86	0.81–0.91	<0.001	15% (13.4–15.9)	19% (16.9–20.3)	<0.001
	Appendix	27.8 (19.8–35.9)	21.7 (15.2–28.3)	33.7 (22.7–44.7)	0.87	0.63–1.21	0.422	30% (20.8–39.0)	29% (19.5–39.4)	0.944
Degree of	Well/moderate	23.6 (22.9–24.4)	20.0 (19.1–21.0)	28.4 (27.0–29.7)	0.76	0.72–0.80	<0.001	21% (19.7–22.1)	28% (26.6–20.1)	<0.001
differentiation^c	Poor/undifferentiated	11.3 (10.6–12.0)	9.6 (8.8–10.4)	14.0 (12.8–15.1)	0.75	0.69–0.81	<0.001	10% (8.3–11.0)	17% (15.219.7)	<0.001
Presentation of	Synchronous	13.1 (12.8–13.5)	12.5 (12.0–13.0)	13.6 (13.1–14.1)	0.91	0.88–0.95	<0.001	12% (11.0–12.6)	14% (13.1–15.2)	<0.001
metastases	Metachronous	17.6 (16.7–18.4)	15.6 (14.4–16.9)	18.8 (17.6–20.0)	0.89	0.84–0.95	<0.001	18% (16.3–19.5)	20% (18.6–22.3)	0.041
	Local recurrence	13.0 (10.8–15.3)	9.2 (6.9–11.5)	16.9 (12.4–21.3)	0.72	0.59–0.87	0.001	17% (12.5–22.0)	26% (20.2–31.1)	0.024
Metastatic sites^d	Liver only	14.4 (13.8–15.0)	13.2 (12.5–14.0)	15.8 (14.8–16.8)	0.85	0.80–0.90	<0.001	16% (15.2–17.8)	22% (20.6–24.1)	<0.001
	Lung only	29.0 (26.6–31.4)	26.4 (13.6–29.2)	31.7 (28.1–35.3)	0.81	0.73–0.91	<0.001	26% (22.5–28.6)	33% (29.7–36.6)	0.001
	One other site	11.5 (10.5–12.5)	8.7 (7.5–10.0)	14.6 (13.0–16.1)	0.73	0.66–0.80	<0.001	12% (9.7–14.0)	18% (14.9–21.1)	0.001
	Local only	11.8 (10.6–13.0)	10.1 (8.0–12.1)	12.9 (11.3–14.5)	0.88	0.76–1.02	0.084	17% (13.3–21.3)	19% (15.2–21.9)	0.650
	Multiple	12.3 (11.8–12.7)	12.5 (11.8–13.2)	12.2 (11.6–12.7)	1.04	0.99–1.09	0.095	8% (6.9–8.7)	6% (5.4–7.4)	0.031
Healthcare region^e	1	14.0 (13.2–14.8)	13.4 (12.3–14.5)	14.3 (13.2–15.5)	0.89	0.82–0.95	<0.001	15% (12.9–16.3)	18% (16.2–20.6)	0.007
	2	14.1 (13.4–14.8)	12.9 (11.9–13.8)	14.8 (13.8–15.7)	0.93	0.88–1.00	0.041	13% (11.4–14.4)	14% (12.1–15.6)	0.440
	3	14.3 (13.2–15.3)	13.2 (11.6–14.7)	15.1 (13.7–16.5)	0.87	0.79–0.96	0.003	14% (11.5–15.8)	17% (14.1–19.9)	0.065
	4	13.0 (12.3–13.8)	11.4 (10.4–12.4)	14.6 (13.4–15.8)	0.85	0.79–0.91	<0.001	13% (10.9–14.1)	16% (14.2–18.2)	0.005
	5	15.0 (14.2–15.9)	14.1 (13.1–15.1)	15.8 (14.4–17.1)	0.89	0.83–0.95	0.001	15% (12.9–16.2)	17% (15.4–19.6)	0.032
	6	14.0 (12.9–15.0)	13.2 (11.6–14.8)	14.8 (13.1–16.4)	0.89	0.81–0.99	0.039	15% (12.9–16.2)	17% (15.4–19.6)	0.027

^a2012–2016 compared to 2007–2011 (reference); ^b113 with unknown/multiple primary tumours excluded; ^c7464 with missing degree of differentiation excluded; ^d114 with unknown metastatic sites excluded; ^e17 with missing information excluded. CI: confidence interval; HR: hazard ratio; OS: overall survival.

Table 3. Univariable and multivariable analyses for effects on overall survival, global p-values for the variables are shown after the reference category (HR = 1).

			Univariable			Multivariable
		N	HR	95% CI	p Value	HR	95% CI	p Value
Time periods	2007–2011	8696	1		<0.001	1		<0.001
	2012–2016	10657	0.89	0.86–0.92	<0.001	0.88	0.85–0.91	<0.001
Age (years)	18–60	3205	1		<0.001	1		<0.001
	61–70	5218	1.11	1.05–1.17	<0.001	1.11	1.05–1.17	<0.001
	71–80	6373	1.49	1.42–1.56	<0.001	1.48	1.41–1.56	<0.001
	81–102	4557	2.46	2.33–2.58	<0.001	2.39	2.27–2.52	<0.001
Sex	Male	10605	1		<0.001	1		0.111
	Female	8748	1.09	1.05–1.12	<0.001	1.03	0.99–1.06	0.111
Primary location^a	Right colon	6659	1		<0.001	1		<0.001
	Left colon	5894	0.70	0.68–0.73	<0.001	0.76	0.73–0.79	<0.001
	Rectum	6572	0.68	0.65–0.70	<0.001	0.73	0.70–0.76	<0.001
	Appendix	228	0.46	0.39–0.54	<0.001	0.55	0.46–0.64	<0.001
Presentation of	Synchronous	13508	1		<0.001	1		<0.001
metastases	Metachronous	5257	0.80	0.77–0.83	<0.001	0.80	0.78–0.83	<0.001
	Local recurrence	588	0.86	0.79–0.95	0.003	0.78	0.70–0.85	<0.001
Healthcare region^b	1	3656	1		0.002	1		<0.001
	2	4480	1.04	0.99–1.10	0.085	0.99	0.94–1.04	0.684
	3	2173	1.02	0.96–1.08	0.562	0.98	0.92–1.04	0.513
	4	3594	1.08	1.02–1.13	0.004	1.06	1.01–1.11	0.033
	5	3776	0.97	0.93–1.02	0.293	0.92	0.87–0.96	0.001
	6	1674	1.04	0.97–1.11	0.255	1.02	0.96–1.09	0.577

^a113 with unknown/multiple primary tumours excluded; ^b17 with missing information excluded. CI: confidence interval; HR: hazard ratio.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.