Screening for colorectal cancer

Figures & data

Figure 1. Observed and predicted age-adjusted incidence rates in the five Nordic countries: cancer of the colorectum. (Reproduced with permission from [1]).

Table I.  Evidence for the (A→C) sequence [5].

Similar distribution of adenomas and CRC

CRC is twice as common when adenomas are present

Adenomas are at least twice as common when CRC is present

The presence of contiguous adenomas and CRC

Patients with polyps ≥ 1 cm in diameter that are not removed have an increased risk of CRC

Removal of adenomas probably reduces risk of later CRC

Adenomas are diagnosed some years before CRC

High risk of metachronous neoplasia in patients with synchronous CRC and adenoma

Clustering among multiple adenomas, multiple CRC and between adenomas and CRC

Familial adenomatous polyposis (FAP) is followed by CRC in nearly 100% of the patients, when colon is left behind

Populations with high risk of CRC have the highest prevalence of adenomas

Table II.  Evidence against the (A→C) sequence [5].

Small CRC without adenomatous remnants

Size of adenomas does not increase with age

Different sex distribution in patients with adenoma and carcinoma

Incidence of CRC in people with an initially adenoma-free colon is no less compared to the normal population

The risk of CRC is still increased after removal of adenomas

Table III.  Flexible Sigmoidoscopy (FS) as a screening instrument.

Type of study Reference	Procedure and Target group	Incidence (Odds Ratio)	Mortality from CRC (Odds Ratio)	Status and Criticism
Case Control Newcomb et al.[68]	66 rectal and distal colonic cancers 196 controls		0.21 (95% C.I. 0.08–0.52) Sigmoidoscopy in 10%∼30%	FS was performed in 66% of endoscopies in cases and 59% of controls. The remaining being rigid sigmoidoscopy
Case Control Müller et al [69] and Müller et al. [70]	8,722 colonic cancers 7,629 rectal cancers 16,531 living controls 16,199 dead controls	Colonic cancer 0.56 (95% C.I. 0.46–0.67) Rectal cancer 0.61 (0.49–0.75)	0.41 (95% C.I. 0.33–0.50)	Complicated design evaluating FS, colonoscopy and polypectomy together
RCT, population based Thiis-Evensen et al. [16]	Once FS Performed FS 324/400 399 controls 50–59 years	0.2 (95% C.I. 0.03–0.95) (P = 0.02) Follow-up 13 year (2 cancers∼10 cancers)	At follow-up 3 controls had died from CRC and one in the screening group	Very small numbers
RCT, volunteer based UK FS-Screening Trial Investigators [32]	Once FS Performed FS 40.675/57.070 2×57,070 controls 55–64 years	No results yet	No results yet	Intake complete year 2000. Selection by letter to 368,597 among whom 194,650 were interested
RCT, volunteer based Segnan et al. [42]	Once FS Performed FS 9,791/16,769 16,679 controls 55–64 years	No results yet	No results yet	Intake completed year 1998. Same selection as in the UK study
RCT, population based Gondal et al. [28]	Once FS ±FOBT Performed FS 12,960 Controls 79,430 50–64 years	No results yet	No results yet	Intake completed year 2001.
RCT Gohagan et al. [17]	FS every 3 years FS 74,000 Controls 74,000 68–74 years	No results yet	No results yet	Planned to stop intake year 2000. Multiphasic screening program for more than one cancer.

Table IV.  Colonoscopy as a screening instrument.

Target group Reference	Accepted colonoscopy	Complete colonoscopy	Screen detected neoplasia	Serious complications	Criticism
Asymptomatic 50–75 years (62.9) 96.8% men; Lieberman et al. [71]	3,196/4,659 68.5%	97.7%	30 CRC (0.9%) 299 significant adenomas (9.3%)	0.3%	Selected population: 13 Veteran Affairs medical centers
Random population sample 63–72 years (67.4); Thiis-Evensen et al. [72]	241/356 67.6%	80.0%	2 CRC (0.8%) 38 high risk adenomas (15.7%)	None	47 had symptoms and 9 had increased risk of CRC
Asymptomatic 50–75 years negative H-II; Rex et al. [73]	210/5.000 4.2%	99.5%	2 CRC (0.9%) 11 subjects with adenomas ≥ 10 mm (5.2%)	0.5%	Selected population: physicians and dentists and their spouses

Table V.  The 3 large RCT's with Hemoccult-II.

Characteristic	Minnesota (50–80 years) [22] (volunteers)	Nottingham (45–74 years) [8] (normal population)	Funen (45–75 years) [10] (normal population)
Test group Controls	15,570 annual, 15.587 biennial 15,394	76,466 biennial 76,384	30,967 biennial 30,966
Period of screening	1975–82, 1986–1992	1981–1995	1985–2002
Positivity rate	9.8%	1.8–0.8%	3.8–0.8%
Pvpos CRC	2% annual, 3% biennial	11–14%	5–21%
Dukes A (%) Test group Controls	30% annual, 27% biennial 22%	20% 11%	22% 11%
Mortality ratio for CRC	0.67(0.51–0.83) (a) 0.79 (0.62–0.97) (b)	0.85 (0.74–0.98)	0.82 (0.68–0.99)

Table VI.  Predicted effect of screening for colorectal cancer on the numbers of deaths and age adjusted “world standard population” mortality rates, females. [2]

	Predicted number of deaths			Predicted mortality rates
Period	Without screening	With screening	Difference	Without screening	With screening	Difference
Denmark
1993–97	5661	5661	–	17.0	17.0	–
1998–02	5879	5434	445	17.1	15.5	1.7
2003–07	5962	5206	756	17.0	14.7	2.4
2008–12	5964	4928	1036	16.7	14.0	2.7
2013–17	6097	5038	1059	16.5	13.8	2.7
Total	29563	26267	3296	16.9	15.0	1.9
Finland
1993–97	2880	2880	–	8.8	8.8	–
1998–02	3019	2793	226	8.7	7.9	0.8
2003–07	3123	2727	396	8.6	7.7	1.4
2008–12	3254	2686	568	8.4	7.0	1.4
2013–17	3335	2752	583	8.2	6.8	1.7
Total	15611	13838	1773	8.5	7.5	1.0
Iceland
1993–97	115	115	–	9.6	9.6	–
1998–02	124	113	11	9.6	8.6	1.0
2003–07	136	117	19	9.6	7.7	1.9
2008–12	148	122	26	9.6	7.5	2.1
2013–17	160	132	28	9.6	7.5	2.1
Total	683	599	84	9.6	8.2	1.4
Norway
1993–97	3877	3877	–	14.0	14.0	–
1998–02	4174	3855	319	14.3	12.8	1.5
2003–07	4397	3850	547	14.2	12.1	2.1
2008–12	4540	3673	867	13.9	11.5	2.4
Total	16988	15255	1733	14.1	12.6	1.5
Sweden
1993–97	6472	6472	–	10.4	10.4	–
1998–02	6557	6071	486	10.0	9.0	1.0
2003–07	6531	5732	799	9.4	8.1	1.4
2008–12	6388	5270	1118	8.7	7.3	1.5
2013–17	6101	5029	1072	7.9	6.6	1.3
Total	32049	28573	3476	9.3	8.3	1.0

Table VII.  Predicted effect of screening for colorectal cancer on the numbers of deaths and age adjusted “world standard population” mortality rates, males. [2]

	Predicted number of deaths			Predicted mortality rates
Period	Without screening	With screening	Difference	Without screening	With screening	Difference
Denmark
1993–97	5070	5070	–	22.1	22.1	–
1998–02	5099	4622	477	21.5	19.3	2.2
2003–07	5147	4406	741	20.9	17.9	3.0
2008–12	5194	4290	904	20.2	16.9	3.4
2013–17	5296	4373	923	19.8	16.5	3.3
Total	25806	22761	3045	20.9	18.5	2.4
Finland
1993–97	2354	2354	–	12.9	12.9	–
1998–02	2634	2383	251	13.0	11.8	1.2
2003–07	2948	2516	432	13.1	11.3	1.8
2008–12	3267	2689	578	12.9	10.7	2.2
2013–17	3595	2956	639	12.8	10.6	2.2
Total	14798	12898	1900	12.9	11.4	1.5
Iceland
1993–97	110	110	–	11.7	11.7	–
1998–02	121	110	11	11.7	10.4	1.2
2003–07	134	114	20	11.7	9.9	1.8
2008–12	149	122	27	11.7	9.6	2.1
2013–17	164	135	29	11.7	9.6	2.1
Total	678	591	87	11.7	10.2	1.4
Norway
1993–97	4174	4174	–	21.8	21.8	–
1998–02	4602	4187	415	23.6	21.2	2.4
2003–07	5075	4367	708	25.4	21.7	3.6
2008–12	5686	4718	968	27.4	22.9	4.5
Total	19537	17446	2091	24.5	21.9	2.6
Sweden
1993–97	6490	6490	–	14.4	14.4	–
1998–02	6647	6045	602	14.1	12.6	1.5
2003–07	6723	5758	965	13.6	11.5	2.0
2008–12	6744	5528	1216	12.8	10.6	2.2
2013–17	6709	5495	1214	11.8	9.8	2.0
Total	33313	29317	3996	13.4	11.8	1.6

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