Colorectal and interval cancers of the Colorectal Cancer Screening Program in the Basque Country (Spain)

Table 1 Characteristic of interval cancers and screen-detected colorectal cancers n (%)

	Interval cancers		Screen-detected (SCs)	P value
	FIT	Post-colonoscopy
Total	186 (6.8)	18 (0.7)	2518 (92.5)	-
Patient characteristics
Sex
Male	125 (67.2)	10 (55.6)	1651 (65.6)	0.601
Female	61 (32.8)	8 (44.4)	867 (34.4)
Age (yr)
Mean (SC)	60.2 (4.9)	62.0 (3.5)	61.7 (3.4)	0.042
50-54	28 (15.1)	0 (0)	375 (14.9)
55-59	53 (28.5)	5 (27.8)	539 (21.4)	0.001
60-64	61 (32.8)	10 (55.6)	709 (28.2)
65-69	44 (23.7)	3 (16.7)	895 (35.5)
Round of invitation				0.001
1	143 (76.9)	16 (88.9)	1615 (64.1)
2	40 (21.5)	2 (11.1)	680 (27.0)
3	3 (1.6)	0 (0)	223 (8.9)
Type participation				0.086
Initial	149 (80.1)	17 (94.4)	1863 (74.0)
Regular	35 (18.8)	1 (5.6)	639 (25.4)
Irregular	2 (1.1)	0 (0)	16 (0.6)
Deprivation Index				0.192
1 (least deprived)	42 (23.9)	3 (16.7)	521 (21.4)
2	43 (24.4)	1 (5.5)	503 (20.6)
3	29 (16.5)	6 (33.4)	539 (22.1)
4	38 (21.6)	2 (11.1)	461 (18.9)
5 (most deprived)	24 (13.6)	5 (27.8)	414 (17.0)
Unknown	0 (0)	1 (5.5)	0 (0)
Time to diagnosis (months)			-	< 0.0001
Median (IQR)	13.5 (8.5-18.9)	28.1 (16.5-40.1)
Range	1.5-39.4	5.6-61.2
Cancer characteristics
Location				< 0.0001
Proximal1	68 (36.6)	7 (38.9)	478 (19.0)
Distal2	58 (31.2)	9 (50.0)	1529 (60.7)
Rectum	58 (31.2)	2 (11.1)	404 (16.0)
Unknown	2 (1.1)	0 (0)	107 (4.2)
Stage				< 0.0001
I	43 (23.1)	4 (22.2)	1376 (54.6)
II	36 (19.4)	2 (11.1)	408 (16.2)
III	57 (30.6)	7 (38.9)	566 (22.5)
IV	50 (26.9)	5 (27.8)	152 (6.0)
Unknown	0 (0)	0 (0)	16 (0.6)
Morphology				0.002
ADC, NOS	139 (74.7)	15 (83.3)	1823 (72.4)
ADC in adenomatous polyp	4 (2.2)	0 (0)	121 (4.8)
Carcinoid tumor	0 (0)	0 (0)	7 (0.3)
ADC in villous adenoma	6 (3.2)	0 (0)	154 (6.1)
ADC in tubulovillous adenoma	10 (5.4)	0 (0)	174 (6.9)
Mucinous ADC	5 (2.7)	2 (11.1)	42 (1.7)
Mucin-producing ADC	3 (1.6)	0 (0)	23 (0.9)
Signet ring cell carcinoma	0 (0)	0 (0)	4 (0.2)
Other	15 (8.1)	0 (0)	64 (2.5)
Unknown	4 (2.2)	1 (5.6)	106 (4.2)
Degree of differentiation				< 0.0001
Well differentiated	76 (41.1)	7 (38.9)	988 (39.2)
Moderately differentiated	59 (31.9)	7 (38.9)	1061 (42.2)
Poorly differentiated	14 (7.6)	1 (5.5)	86 (3.4)
Undifferentiated/anaplastic	33 (17.8)	2 (11.1)	320 (12.7)
Unknown	3 (1.6)	1 (5.5)	63 (2.5)
Size (mm)				0.022
Median (IQR)	20 (8.0-40.0)	38.0 (30.0-60.0)	26.0 (19.7-40.0)
Range	2.0-90.0	9.0-80.0	2.0-95.0
Treatment				< 0.0001
Endoscopic resection	5 (2.7)	0 (0)	733 (29.1)
Surgery	56 (30.1)	9 (50.0)	182 (7.2)
Surgery and neoadjuvant therapy	106 (57.0)	7 (38.9)	1332 (52.9)
Palliative procedure	18 (9.7)	2 (11.1)	164 (6.6)
Unknown	1 (0.5)	0 (0)	107 (4.2)

¹Cecum, Ascending, Hepatic Flexure, and Transverse;

²Splenic Flexure, Descending, Sigmoid. ADC: Adenocarcinoma; FIT: Faecal inmunochemical test.

Table 2 f-Hb values of previous negative screening test in interval cancer cases

	Median f-Hb (μg Hb/g faeces)	IQR	P value
All	2.8	0.4-9.9	-
Sex
Male	3.4	0.2-10.0	0.409
Female	1.9	0.4-9.8
Age (yr)			0.380
50-54	1.9	0.2-6.9
55-59	3.0	0.6-13.0
60-64	2.8	0.2-8.6
65-69	4.0	0.4-12.5
Deprivation Index			0.887
1 (least deprived)	3.0	0.6-11.9
2	2.6	0.0-10.2
3	4.2	1.1-12.4
4	4.0	0.4-11.2
5 (most deprived)	2.6	0.0-8.7
Time to diagnosis (mo)			0.795
Within 1 yr	3.4	0.2-10.6
1-2 yr	2.5	0.5-9.6
Location			0.171
Proximal1	1.9	0.0-9.3
Distal2	3.8	0.3-13.7
Rectum	3.9	0.7-9.1
Unknown	1.0	0.0-…
Stage			0.927
I	2.0	0.0-9.7
II	2.6	0.2-10.6
III	3.2	0.7-9.8
IV	4.0	0.2-9.9
Unknown
Morphology			0.550
ADC, NOS	3.0	0.6-10.0
ADC in adenomatous polyp	10.0	2.0-17.2
ADC in villous adenoma	0.5	0.0-9.8
ADC in tubulovillous adenoma	2.4	0.0-9.3
Mucinous ADC	0.4	0.0-12.5
Mucin-producing ADC	14.0	0.0-…
Other	1.7	0.0-6.0
Unknown	1.0	0.0-6.9
Degree of differentiation			0.600
Well differentiated	2.8	1.0-9.0
Moderately differentiated	4.4	0.6-13.0
Poorly differentiated	0.6	0.0-5.6
Undifferentiated/anaplastic	4.0	0.0-9.4
Unknown	2.0	0.0-…
Size (mm)
< 10	1.4	0.4-12.4	0.586
10-19.99	1.0	0.0-7.9
≥ 20	2.9

¹Caecum, ascending, hepatic flexure, transverse;

²Splenic flexure, descending. ADC: Adenocarcinoma; IQR: Interquartile range.

Table 3 Characteristics of post colonoscopy colorectal cancers at the time of diagnosis

	n (%)
Interval CRC tumor site
Appendix and caecum	5 (27.8)
Ascending	0 (0)
Hepatic flexure	1 (5.6)
Transverse	1 (5.6)
Splenic flexure	0 (0)
Descending	2 (11.1)
Sigmoid	7 (38.8)
Rectum	2 (11.1)
Unknown	0 (0)
Polyp found on the Screening colonoscopy
Yes	10 (61.1)
No	8 (38.9)
Polyp frequency
Median (IQR)	2.0 (1.0-3.5)
Range	1-6
Previous resection in the same location
Yes	2 (11.0)
No	16 (89.0)
Report of incomplete Screening colonoscopy
Yes2	3 (16.7)
No	15 (83.3)
Polyp size on the Screening colonoscopy
≥ 10 mm
Yes	2 (11.1)
No	16 (88.9)
Polyp histology (n = 10)
Hyperplastic polyp	0 (0)
LRA	6 (60.0)
AA	4 (40.0)
Bowel preparation
Inadequate	2 (11.1)
Adequate1	12 (66.7)
Unknown	4 (22.2)
Diverticulosis
Yes	5 (27.8)
No	13 (72.2)

¹Boston scale ≥ 7;

²Complementary radiological test (Barium Enema or Computerized Tomography) was performed after colonoscopy. AA: Advanced adenoma; LRA: Low risk adenoma; CRC: Colorectal cancer; IQR: Interquartile range.

Table 4 Multivariate analysis of patients and tumors predictors of interval cancers compared with screen-detected cancers

	% with CI	OR (95%CI)	P value
Sex
Female	69 (33.8)	1 (ref.)
Male	135 (66.2)	1.03 (0.76-1.39)	0.860
Age (yr)
50-54	28 (13.7)	1 (ref.)
55-59	58 (28.4)	1.44 (0.90-2.31)	0.127
60-64	71 (34.8)	1.34 (0.84-2.11)	0.206
65-69	47 (23.0)	0.70 (0.43-1.14)	0.153
Deprivation
1 (least deprived)	45 (23.3)	1 (ref.)
2	44 (22.8)	1.01 (0.66-1.56)	0.954
3	35 (18.1)	0.75 (0.48-1.19)	0.222
4	40 (20.7)	1.00 (0.64-1.57)	0.984
5 (most deprived)	29 (15.0)	0.81 (0.50-1.32)	0.396
Location
Proximal1	74 (36.8)	1 (ref.)
Distal2	67 (33.3)	0.28 (0.20-0.40)	< 0.0001
Rectum	60 (29.9)	0.96 (0.67-1.38)	0.824
Stage
I	47 (23.0)	1 (ref.)
II	38 (18.6)	2.73 (1.75-4.24)	< 0.0001
III	64 (31.4)	3.31 (2.24-4.88)	< 0.0001
IV	55 (27.0)	10.59 (6.93-16.18)	< 0.0001

¹Caecum, ascending, hepatic flexure, transverse;

²Splenic flexure, descending.

Table 5 Hazard ratios and 95%CI for interval cancer vs screen-detected cancers

	Hazard ratio	95% CI	P value
Sex
Female (ref)
Male	1.39	1.01-1.93	0.049
Age (yr)
50-54 (ref)			0.451
55-59	1.37	0.79-2.36	0.258
60-64	1.22	0.72-2.07	0.463
65-69	1.47	0.89-2.44	0.137
Deprivation Index
1 (least deprived) (ref)			0.839
2	0.89	0.54-1.46	0.639
3	1.01	0.63-1.62	0.956
4	0.90	0.54-1.51	0.696
5 (most deprived)	1.16	0.72-1.88	0.537
Location
Rectum (ref)			< 0.001
Proximal1	1.17	0.78-1.77	0.456
Distal2	0.56	0.39-0.82	0.003
Stage
I (ref)			< 0.001
II	1.99	1.11-3.54	0.020
III	3.67	2.31-5.83	< 0.001
IV	26.54	17.37-40.56	< 0.001
CRC type
Screen detected CRC (ref)			< 0.0001
IC FIT	3.31	2.25-4.85	< 0.0001
IC colonoscopy	3.49	1.11-10.97	0.032

¹Caecum, ascending, hepatic flexure, transverse;

²Splenic flexure, descending.