Fecal immunochemical test in cancer screening – colonoscopy outcome in FIT positives and negatives

Figures & data

Figure 1. Flowchart of study participants. AN: advanced neoplasia (adenocarcinoma and advanced adenoma); non-AN: non-advanced adenoma, other findings or normal colonoscopy.

Table 1. Basic variables in 806 colonoscopy screening participants.

Variable	All participants (n = 806), N (%)	Participants with FIT <10 µg/g (n = 704), N (%)	Participants with at least one of two FIT ≥10 µg/g (n = 102), N (%)
Gender
Men	390 (48)	334 (47)	56 (55)
Women	416 (52)	370 (53)	46 (45)
NSAID
Yes	49 (6.0)	43 (6.1)	6 (5.8)
No	750 (93)	656 (93)	94 (92)
Missing	7 (1.0)	5 (0.7)	2 (2.0)
ASA
Yes	67 (8.3)	54 (7.7)	13 (13)^b
No	735 (91)	647 (92)	88 (86)
Missing	4 (0.5)	3 (0.4)	1 (1.0)
BMI
Median [range]	26.1 [17.0–44.3]	25.9 [17.9–42.7]	26.8 [17.0–44.3]
Missing	1 (0.1)	1 (0.1)	0 (0.0)
Caecal intubation	781 (97)	684 (97)	97 (95)
Caecal withdrawal time >6 min	781 (97)	682 (97)	99 (97)
Bowel preparation. Boston scale ≥2	790 (98)	693 (98)	97 (95)
Colonoscopy findings^a
CRC	1 (0.1)	0 (0.0)	1 (1.0)
AA	80 (9.9)	60 (8.5)	20 (20)
Non-AA	145 (18)	131 (19)	14 (14)
Other	230 (29)	197 (28)	33 (32)
Normal	350 (43)	316 (45)	34 (33)
Number of adenomas/participant
[range]	[0–35]	[0–8]	[0–35]
1	160 (20)	136 (19)	24 (24)
2	42 (5.2)	36 (5.1)	6 (5.8)
≥3	23 (2.9)	19 (2.7)	4 (3.9)
AA (n = 80)	Participants with AA, N = 80 (%)	AA Participants with FIT <10 µg/g, N = 60 (%)	AA participants with ≥1 of 2 FIT ≥10 µg/g, N = 20 (%)
Size <10 mm	31 (39)	27 (87)	4 (13)
Localization
Proximal	36 (45)	33 (92)	3 (8.3)
Distal	26 (33)	13 (50)	13 (50)
Both	18 (23)	14 (78)	4 (22)
Histology
Tubular	19 (24)	14 (74)	5 (26)
SSA/HP no dysplasia	14 (18)	14 (100)	0 (0)
LGD	47 (59)	36 (77)	11 (23)
Shape
Pedunculated	13 (16)	4 (31)	9 (69)
Flat or broad based	67 (84)	56 (84)	11 (16)
Gender
Men	46 (58)	30 (65)	16 (35)
Women	34 (43)	30 (88)	4 (12)

NSAIDs: non-steroidal anti-inflammatory drugs; ASA: acetylsalicylic acid; BMI: body mass index; CRC: colorectal cancer; AA: adenoma ≥10 mm or ≥3 < 10 mm or adenomas with villous growth or high grade dysplasia; non-AA: ≤2 tubular adenomas <10 mm with low grade dysplasia; other: diverticular disease, hemorrhoids, angiodysplasia or inflammation; FIT: fecal immunochemical test; Prox: caecum-splenic flexure; Dist: descendens-rectum; SSA/HP no dysplasia: sessile serrated adenoma/polyp or hyperplastic polyp ≥10 mm without dysplasia; LGD: low grade dysplasia.

^aAccording to most advanced lesion.

^bThe difference in proportion of ASA medication between FIT positives and negatives is non-significant.

Table 2. Sensitivity and specificity for advanced neoplasia at different fecal immunochemical test (FIT) cut off levels and number of samples in 806 screening participants.

Test, cut off (µg/g)	Positivity (95% CI)	True positive	False positive	True negative	False negative	Sensitivity^d (95% CI)	Specificity^e (95% CI)	PPV (95% CI)	NPV (95% CI)
≥1 of 2^a 10	12.7 (10.4–15.0)	21	81	644	60	25.9 (16.8–36.9)	88.8 (86.3–91.0)	20.6 (13.2–29.7)	91.5 (89.2–93.4)
20	7.2 (5.4–9.0)	19	39	686	62	23.5 (14.8–34.2)	94.6 (92.7–96.1)	32.8 (21.0–46.3)	91.7 (89.5–93.6)
40	3.7 (2.4–5.0)	13	17	708	68	16.0 (8.80–25.9)	97.7 (96.3–98.6)	43.3 (25.5–62.6)	91.2 (89.0–93.1)
60	2.5 (1.4–3.6)	10	10	715	71	12.3 (6.10–21.5)	98.6 (97.5–99.3)	50.0 (27.2–72.8)	91.0 (88.7–92.9)
80	2.2 (1.2–3.3)	9	9	716	72	11.1 (5.20–20.0)	98.8 (97.7–99.4)	50.0 (27.2–72.8)	90.9 (88.6–92.8)
Mean^b 10	9.6 (7.6–11.7)	20	57	662	61	24.7 (15.8–35.5)	92.1 (89.9–93.9)	26.0 (16.6–37.2)	91.6 (89.3–93.5)
20	4.6 (3.2–6.1)	14	23	696	67	17.3 (9.80–27.3)	96.8 (95.2–98.0)	37.8 (22.5–55.2)	91.2 (89.0–93.1)
40	2.6 (1.5–3.7)	11	10	709	70	13.6 (7.00–23.0)	98.6 (97.5–99.3)	52.4 (29.8–74.3)	91.0 (88.8–92.9)
60	2.1 (1.1–3.1)	8	9	710	73	9.90 (4.40–18.5)	98.7 (97.6–99.4)	47.1 (23.0–72.2)	90.7 (88.4–92.6)
80	1.8 (0.8–2.7)	6	8	711	75	7.40 (2.80–15.4)	98.9 (97.8–99.5)	42.9 (17.7–71.1)	90.5 (88.2–92.4)
First^c 10	8.6 (6.6–10.5)	16	53	672	65	19.8 (11.7–30.1)	92.7 (90.5–94.5)	23.2 (13.9–34.9)	91.2 (88.9–93.1)
20	4.2 (2.8–5.6)	12	22	703	69	14.8 (7.90–24.4)	97.0 (95.4–98.1)	35.3 (19.8–53.5)	91.1 (88.8–93.0)
40	2.4 (1.3–3.4)	8	11	714	73	9.90 (4.40–18.5)	98.5 (97.3–99.2)	42.1 (20.3–66.5)	90.7 (88.5–92.7)
60	1.6 (0.7–2.5)	6	7	718	75	7.40 (2.80–15.4)	99.0 (98.0–99.6)	46.2 (19.2–74.9)	90.5 (88.3–92.5)
80	1.6 (0.7–2.5)	6	7	718	75	7.40 (2.80–15.4)	99.0 (98.0–99.6)	46.2 (19.2–74.9)	90.5 (88.3–92.5)

Advanced neoplasia: adenocarcinoma or advanced adenoma (=adenoma ≥10 mm or ≥3 < 10 mm or adenomas with villous growth or high grade dysplasia); PPV: positive predictive value; NPV: negative predictive value.

^aAt least one of two samples above or equal to cut off.

^bMean of two samples above cut off. Six participants were excluded as they sent only one sample.

^cFirst of two samples. In 48 participants, both tests are from the same date, therefore a random sample was chosen as the first FIT.

^dThe differences in sensitivity for each cut off level are non-significant.

^eThe differences in specificity for each cut off level are non-significant except for ≥1 of two samples and first sample at cut off 10 µg/g (p = .02) and ≥1 of two samples and first sample at cut off 20 µg/g (p = .04).

Table 3. Univariate analysis of adenoma characteristics and FIT positivity in 225 colonoscopy screening participants with adenomas, of which 160 had only one adenoma.

	All participants with adenoma, n = 225			Participants with only one adenoma, n = 160
	FIT pos, n = 34 (%)	FIT neg, n = 191 (%)	p Value	FIT pos, n = 24 (%)	FIT neg, n = 136 (%)	p Value
Total number (1–35)	–	–	.876	–	–	–
Localization
Prox only	9 (8)	103 (92)	.004	9 (10)	79 (90)	.062
Dist only	20 (22)	70 (78)		15 (21)	57 (79)
Both	5 (22)	18 (78)		–	–
Histology
Tubular	16 (11)	133 (89)		14 (13)	97 (87)
Tubulovillous	13 (45)	16 (55)	<.001*	7 (37)	12 (63)	.004*
Villous	1 (50)	1 (50)		1 (50)	1 (50)
SSA + tubular	1 (11)	8 (89)		–	–
SSA	3 (9)	30 (91)		2 (8)	23 (92)
HP	0 (0)	3 (100)		0 (0)	3 (100)
Shape
Pedunculated	13 (54)	11 (46)		9 (53)	8 (47)
Broad based	10 (9)	104 (91)	<.001**	8 (10)	75 (90)	<.001**
Flat	11 (13)	76 (87)		7 (12)	53 (88)
Size
<5 mm	5 (5)	101 (95)	<.001	5 (6)	80 (94)	.002
5–9 mm	13 (19)	57 (81)		11 (24)	34 (76)
10–19 mm	10 (31)	22 (69)		6 (29)	15 (71)
>19 mm	6 (35)	11 (65)		2 (22)	7 (78)
Dysplasia
LGD	24 (13)	154 (87)	<.001***	17 (13)	109 (87)	.001***
HGD	7 (78)	2 (22)		5 (83)	1 (17)
SSA dysplasia	2 (20)	8 (80)	<.001****	1 (20)	4 (80)	.002****
SSA no dysplasia	1 (4)	24 (96)		1 (5)	19 (95)
HP no dysplasia	0 (0)	3 (100)		0 (0)	3 (100)
Gender
Men	25 (22)	91 (78)	.005	16 (21)	61 (79)	.049
Women	9 (8)	100 (92)		8 (10)	75 (90)

FIT pos: at least one of two samples ≥10 µg/g; Prox: caecum-splenic flexure; Dist: descendens-rectum; SSA: sessile serrated adenoma/polyp; HP: hyperplastic polyp ≥10 mm; SSA + tubular: synchronous SSA and tubular adenoma; LGD: low grade dysplasia; HGD: high grade dysplasia.

*Tubulovillous or villous vs. tubular or SSA + tubular.

**Broad based or flat vs. pedunculated.

***HGD vs. LGD.

****High-risk dysplasia (HGD or SSA dysplasia) vs. low-risk dysplasia (LGD, SSA/HP no dysplasia).

Table 4. Odds ratio for FIT positivity (at least one of two samples ≥10 µg hemoglobin/g) in 225 screening participants with adenoma.

Variable	Odds ratio	95% CI	p Value
Number of adenomas^a	1.12	0.94–1.32	.209
Growth pattern
HP/SSA/tubular + SSA	1 (ref)
Tubular	2.38	0.50–11.5	.279
Tubulovillous or villous	7.35	1.36–39.7	.020
Dysplasia
Low-risk dysplasia	1 (ref)
High-risk dysplasia	7.34	1.64–32.8	.009
Localization
Proximal	1 (ref)
Distal	1.66	0.57–4.83	.355
Both	0.86	0.16–4.47	.853
Size
<5 mm	1 (ref)
5–9 mm	2.85	0.82–9.90	.099
10–19 mm	3.28	0.64–16.9	.156
≥20 mm	3.06	0.41–22.8	.276
Gender
Men	1 (ref)
Women	0.35	0.13–0.93	.036
Shape
Flat/broad based	1 (ref)
Pedunculated	5.09	1.57–16.5	.007

FIT: fecal immunochemical test; CRC: colorectal cancer; SSA/HP: sessile serrated adenoma/hyperplastic polyp >9 mm; tubular + SSA: synchronous SSA and tubular adenoma; low-risk dysplasia: low grade dysplasia in an adenoma, or no dysplasia in SSA; high-risk dysplasia; high grade dysplasia in an adenoma, or dysplasia in SSA; proximal: caecum to splenic flexure.

^aRegardless of adenoma size.