A Comparison of Single and Combined Schemes of Asia-Pacific Colorectal Screening, Faecal Immunochemical and Stool Deoxyribonucleic Acid Testing for Community Colorectal Cancer Screening

Figures & data

Table 1 Characteristics of the Study Population at Baseline Stratified by the Lesion Groups

Characteristic	Total N=100	Positive Results n=71	Negative Results n=29	P value
Sex, n (%)
Male	63 (63.0)	47 (66.2)	16 (55.2)	0.300
Female	37 (37.0)	24 (33.8)	13 (44.8)
Age, median (P25, P75), years	58.0 (53.25, 66.0)	59 (54,67)	56 (53,59)	0.077
Cigarette smoking, n (%)
Non-smoker	51 (51.0)	37 (52.1)	14 (48.3)	0.728
Current smoker or former smoker	49 (49.0)	34 (47.9)	15 (51.7)
Regular alcohol drinking, n (%)
No	71 (71.0)	49 (69.0)	22 (75.9)	0.493
Yes	29 (29.0)	22 (31.0)	7 (24.1)
Family history of colorectal cancer among the first-degree relatives, n (%)
No	69 (69.0)	51 (71.8)	18 (62.1)	0.338
Yes	31 (31.0)	20 (28.2)	11 (37.9)

Figure 1 Flowchart of the participants.

Abbreviations: FIT, fecal immunochemical test; sDNA, stool DNA.

Table 2 The Sensitivity and Specificity of the Single and Combined Complementary Primary Screening Schemes

	Colonoscopy	APCS	FIT	sDNA Test	APCS+FIT	APCS+sDNA Test	FIT+sDNA test	APCS+FIT+sDNA Test	P value
CRC
Positive	2	0	2	2	2	2	2	2
Sensitivity (95% CI)		0	100.0 (15.8–100.0)	100.0 (15.8–100.0)	100.0 (15.8–100.0)	100.0 (15.8–100.0)	100.0 (15.8–100.0)	100.0 (15.8–100.0)	0.143
AA
Positive	24	17	10	12	21	23	15	24
Sensitivity (95% CI)		70.8 (48.9–87.4)	41.7 (22.1–63.4)	50.0 (29.1–70.9)	87.5 (67.6–97.3)	95.8 (78.9–99.9)	62.5 (40.6–81.2)	100.0 (85.5–100.0)	<0.001
HGIN
Positive	1	1	1	1	1	1	1	1
Sensitivity (95% CI)		100.0 (2.5–100.0)	100.0 (2.5–100.0)	100.0 (2.5–100.0)	100.0 (2.5–100.0)	100.0 (2.5–100.0)	100.0 (2.5–100.0)	100.0 (2.5–100.0)	–
ACN
Positive	26	17	10	12	23	25	17	26
Sensitivity (95% CI)		65.4 (44.3–82.8)	46.2 (26.6–66.6)	53.8 (33.4–73.4)	88.5 (69.8–97.6)	96.2 (80.4–99.9)	65.4 (44.3–82.8)	100.0 (86.8–100.0)	<0.001
NAA
Positive	45	28	6	19	32	41	24	45
Sensitivity (95% CI)		62.2 (46.5–76.2)	13.3 (5.1–26.8)	42.2 (27.7–57.8)	71.1 (55.7–83.6)	91.1 (78.8–97.5)	53.3 (37.9–68.3)	100.0 (92.1–100.0)	<0.001
LGIN
Positive	43	28	6	17	32	39	22	43
Sensitivity (95% CI)		65.1 (49.1–79.0)	14.0 (5.3–27.9)	39.5 (25.0–55.6)	74.4 (58.8–86.5)	90.7 (77.9–97.4)	51.2 (35.5–66.7)	100.0 (91.8–100.0)	<0.001
Positive results
Positive	71	45	18	33	55	66	41	71
Sensitivity (95% CI)		63.4 (51.1–74.5)	25.4 (15.8–37.1)	46.5 (34.5–58.7)	77.5 (66.0–86.5)	93.0 (84.3–97.7)	57.7 (45.4–69.4)	100.0 (94.9–100.0)	<0.001
Negative results
Negative	29	7	26	23	4	3	20	–
Specificity (95% CI)		24.1 (10.3–43.5)	89.7 (72.6–97.8)	79.3 (60.3–92.0)	13.8 (3.9–31.7)	10.3 (2.2–27.4)	69.0 (49.2–84.7)	–	<0.001

Note: -, Constant, and no statistics were calculated.

Abbreviations: 95% CI, 95% confidence intervals; AA, advanced adenoma; ACN, advanced colorectal neoplasia; APCS, Asia-Pacific Colorectal Screening; CRC, colorectal cancer; FIT, fecal immunochemical test; HGIN, high-grade intraepithelial neoplasia; LGIN, low-grade intraepithelial neoplasia; NAA, nonadvanced adenoma; sDNA, stool DNA.

Table 3 The Kappa Value of the Single and Combined Complementary Primary Screening Schemes

	Colonoscopy	APCS	FIT	sDNA Test	APCS+FIT	APCS+sDNA Test	FIT+sDNA Test	APCS+FIT+sDNA Test
Positive results	71
Kappa (95% CI)		−0.120 (−0.304–0.064)	0.099 (−0.005–0.203)	0.194 (0.045–0.343)	−0.096 (−0.270–0.078)	0.042 (−0.117–0.201)	0.220 (0.046–0.394)	–
P value		0.228	0.095	0.016	0.321	0.581	0.015	–
ACN	26
Kappa (95% CI)		−0.102 (−0.337–0.133)	0.289 (0.066–0.512)	0.259 (0.014–0.504)	0.022 (−0.147–0.191)	0.062 (−0.065–0.189)	0.344 (0.095–0.593)	–
P value		0.393	0.014	0.044	0.802	0.354	0.011	–
AA	24
Kappa (95% CI)		−0.048 (−0.275–0.179)	0.326 (0.091–0.561)	0.300 (0.047–0.553)	0.012 (−0.157–0.181)	0.057 (−0.070–0.184)	0.315 (0.058–0.572)	–
P value		0.679	0.008		0.89	0.397	0.022	–
NAA	45			0.025
Kappa (95% CI)		−0.141 (−0.357–0.075)	0.024 (−0.098–0.146)	0.192 (0.004–0.380)	−0.163 (−0.359–0.033)	0.017 (−0.144–0.178)	0.208 (−0.002–0.418)	–
P value		0.221	0.701	0.056	0.132	0.835	0.06	–
LGIN	43
Kappa (95% CI)		−0.112 (−0.332–0.108)	0.030 (−0.097–0.157)	0.169 (−0.021–0.359)	−0.128 (−0.324–0.068)	0.012 (−0.149–0.173)	0.189 (−0.025–0.403)	–
P value		0.332	0.65	0.093	0.227	0.884	0.091	–

Note: -, Constant, and no statistics were calculated.

Abbreviations: 95% CI, 95% confidence intervals; AA, advanced adenoma; ACN, advanced colorectal neoplasia; APCS, Asia-Pacific Colorectal Screening; FIT, fecal immunochemical test; LGIN, low-grade intraepithelial neoplasia; NAA, nonadvanced adenoma; sDNA, stool DNA.

Figure 2 The sensitivity and specificity of the pairwise comparisons. (A) The sensitivity of the pairwise comparisons for AA; (B) The sensitivity of the pairwise comparisons for ACN; (C) The sensitivity of the pairwise comparisons for NAA; (D) The sensitivity of the pairwise comparisons for LGIN; (E) The sensitivity of the pairwise comparisons for Positive results; (F) The specificity of the pairwise comparisons. a1, b1, c1, d1, e1, f1, APCS; a2, b2, c2, d2, e2, f2, FIT; a3, b3, c3, d3, e3, f3, sDNA test; a4, b4, c4, d4, e4, f4, APCS + FIT; a5, b5, c5, d5, e5, f5, APCS + sDNA test; a6, b6, c6, d6, e6, f6, FIT + sDNA test; a7, b7, c7, d7, e7, f7, APCS + FIT + sDNA test.

Abbreviations: AA, advanced adenoma; ACN, advanced colorectal neoplasia; APCS, Asia-Pacific Colorectal Screening; FIT, fecal immunochemical test; LGIN, low-grade intraepithelial neoplasia; NAA, nonadvanced adenoma; sDNA, stool DNA.

Table 4 The Double Positive Detection of the Combined Primary Screening Schemes

	Colonoscopy	APCS+FIT	APCS+sDNA Test	FIT+sDNA Test	APCS+FIT+sDNA Test	P value
CRC
Positive	2	0	0	2	0
Sensitivity (95% CI)		0.0 (-)	0.0 (-)	100.0 (15.8–100.0)	0.0 (-)	0.250
AA
Positive	24	6	6	7	4
Sensitivity (95% CI)		25.0 (9.8–46.7)	25.0 (9.8–46.7)	29.2 (12.6–51.1)	16.7 (4.7–37.4)	0.438
HGIN
Positive	1	1	1	1	1
Sensitivity (95% CI)		100.0 (2.5–100.0)	100.0 (2.5–100.0)	100.0 (2.5–100.0)	100.0 (2.5–100.00)	-
ACN
Positive	26	6	6	9	4
Sensitivity (95% CI)		23.1 (9.0–43.6)	23.1 (9.0–43.6)	34.6 (17.2–55.7)	15.4 (4.4–34.9)	0.129
NAA
Positive	45	2	6	1	1
Sensitivity (95% CI)		4.4 (0.5–15.1)	13.3 (5.1–26.8)	2.2 (0.1–11.8)	2.2 (0.1–11.8)	0.010
LGIN
Positive	43	2	6	1	1
Sensitivity (95% CI)		4.7 (0.6–15.8)	14.0 (5.3–27.9)	2.3 (0.1–12.3)	2.3 (0.1–12.3)	0.010
Positive results
Positive	71	8	12	10	5
Sensitivity (95% CI)		11.3 (5.0–21.0)	16.9 (9.0–27.7)	14.1 (7.0–24.4)	7.0 (2.3–15.7)	0.068

Notes: -, Constant, and no statistics were calculated.

Abbreviations: 95% CI, 95% confidence intervals; AA, advanced adenoma; ACN, advanced colorectal neoplasia; APCS, Asia-Pacific Colorectal Screening; CRC, colorectal cancer; FIT, fecal immunochemical test; HGIN, high-grade intraepithelial neoplasia; LGIN, low-grade intraepithelial neoplasia; NAA, nonadvanced adenoma; sDNA, stool DNA.

Figure 3 The double positive sensitivity of the pairwise comparisons. (A) The double positive sensitivity of the pairwise comparisons for ACN; a1, APCS + FIT; a2, APCS + sDNA test; a3, FIT + sDNA test; a4, APCS + FIT + sDNA test; (B) the double positive sensitivity of the pairwise comparisons for LGIN; b1, APCS + FIT; b2, APCS + sDNA test; b3, FIT + sDNA test; b4, APCS + FIT + sDNA test.

Abbreviations: ACN, advanced colorectal neoplasia; APCS, Asia-Pacific Colorectal Screening; FIT, fecal immunochemical test; LGIN, low-grade intraepithelial neoplasia; sDNA, stool DNA.

Figure 4 ROC curves comparing different detection schemes for ACN, NAA and positive results. (A) For ACN; (B) For NAA; (C) For positive results. For ACN, FIT AUC was 0.679 (95% CI: 0.534–0.824, P = 0.023), FIT + sDNA test combined scheme AUC was 0.672 (95% CI: 0.527–0.817, P = 0.029). For NAA, AUC (0.611, 95% CI: 0.480–0.743) of FIT + sDNA test combined scheme, with no significant difference. For all lesions positive results, the AUC of FIT + sDNA test combined scheme was 0.634 (95% CI: 0.514–0.753, P = 0.037).

Abbreviations: ACN, advanced colorectal neoplasia; AUC, area under area under the receiver operating characteristic curve; NAA, nonadvanced adenoma; ROC, receiver operating characteristic; SE, standard error.