Multitarget stool DNA for colorectal cancer screening: A review and commentary on the United States Preventive Services Draft Guidelines

Table 1 Findings from the DeeP-C cross-sectional study[5], comparing multitarget stool DNA with fecal immunological test using colonoscopy as the reference standard on all cases (n = 9989 subjects)

	Colonoscopy findings	mt-sDNA	FIT
	n detected	% detected	% detected
Sensitivity
Colorectal cancer (stages I-IV)	65	92.3%	73.8%
Early stage colorectal cancer (stage I and II)	50	94.0%	70.0%
AA	757	42.4%	23.8%
High grade dysplasia	39	69.2%	46.2%
Sessile serrated adenoma/polyp ≥ 1.0 cm	99	42.4%	5.1%
Specificity
Specificity (only CRC and AA excluded)	9167	86.6%	94.9%
Specificity, no adenomas, no biopsy done	4457	89.8%	96.4%
Age-adjusted (50-74 yr)[31]	4032	92.3%	97.0%

FIT: Fecal immunological test; AA: Advanced adenoma.

Table 2 American Cancer Society recommended colorectal cancer screening test frequency intervals for average risk individuals

Test	Frequency (yr)
Colonoscopy	10
CT colonography	5
Flexible sigmoidoscopy	5
Multi-target stool DNA test (Cologuard, mt-sDNA)	3
High sensitivity guaiac-based fecal occult blood test	1
Fecal immunochemical test	1

CT: Computed tomography.

Table 3 Burdens, harms, benefits, and efficiencies for 100% perfect adherence for colorectal cancer screening tests at current recommended intervals, ages 50-75, per 1000 people screened

		Burdens and harms			Benefits
CISNETmodel	Test	Stool tests	Total COL	Complications	LYG	CRC DA	CRC incidence reduction	CRC mortality reduction	% of COL 10y LYG	COL per LYG	Complications per LYG	Complications per DA
SimCRC	COL 10y	0	4007	14	275	24	81%	87%	100%	15	0.051	0.58
	FIT1y	15778	1739	10	260	23	67%	81%	95%	7	0.038	0.43
	hsFOBT1y	12914	2230	11	261	23	69%	82%	95%	9	0.042	0.48
	mt-sDNA3y	5990	1701	9	250	22	63%	78%	91%	7	0.036	0.41
MISCAN	COL 10y	0	4101	15	248	22	62%	79%	100%	17	0.060	0.68
	FIT1y	15843	1757	10	231	20	47%	72%	93%	8	0.043	0.50
	hsFOBT1y	12927	2287	11	232	20	49%	73%	94%	10	0.047	0.55
	mt-sDNA3y	5779	1714	9	215	19	43%	68%	87%	8	0.042	0.47
CRC-SPIN	COL 10y	0	4049	15	270	24	88%	90%	100%	15	0.056	0.62
	FIT1y	15444	1899	11	244	22	72%	81%	90%	8	0.045	0.50
	hsFOBT1y	13026	2253	11	247	22	75%	82%	92%	9	0.045	0.50
	mt-sDNA3y	5927	1827	10	226	20	68%	76%	84%	8	0.044	0.50

CISNET: National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network; SimCRC: Simulation model of colorectal cancer; MISCAN: Microsimulation screening analysis; CRC-SPIN: Colorectal cancer simulated population model for incidence and natural history; COL: Colonoscopies; LYG: Life-years gained; DA: Deaths averted; COL 10y: Colonoscopy at a 10-year interval.

Table 4 Burdens, harms, benefits, and efficiencies at 2-year adherence rates for fecal immunological technique/fecal occult blood testing compared to recommended intervals for colonoscopy and mt-sDNA, ages 50-75, per 1000 people screened

		Burdens and harms			Benefits
CISNETmodel	Test	Stool tests	Total COL	Complications	LYG	CRC DA	CRC incidence reduction	CRC mortality reduction	% of COL 10y LYG	COL per LYG	Complications per LYG	Complications per DA
SimCRC	COL 10y	0	4007	14	275	24	81%	87%	100%	15	0.051	0.58
	FIT2y	9326	1215	7	234	20	53%	72%	85%	5	0.030	0.35
	hsFOBT2y	8388	1597	9	235	21	56%	73%	86%	7	0.038	0.43
	mt-sDNA3y	5990	1701	9	250	22	63%	78%	91%	7	0.036	0.41
MISCAN	COL 10y	0	4101	15	248	22	62%	79%	100%	17	0.060	0.68
	FIT2y	9342	1243	8	200	17	35%	62%	81%	6	0.040	0.47
	hsFOBT2y	8408	1636	9	200	18	37%	63%	81%	8	0.045	0.50
	mt-sDNA3y	5779	1714	9	215	19	43%	68%	87%	8	0.042	0.47
CRC-SPIN	COL 10y	0	4049	15	270	24	88%	90%	100%	15	0.056	0.62
	FIT2y	9241	1346	9	207	18	58%	68%	77%	6	0.043	0.50
	hsFOBT2y	8448	1626	9	212	19	62%	70%	78%	8	0.042	0.47
	mt-sDNA3y	5927	1827	10	226	20	68%	76%	84%	8	0.044	0.50

CISNET: National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network; CRC: Colorectal cancer; SimCRC: Simulation model of CRC; MISCAN: Microsimulation screening analysis; CRC-SPIN: Colorectal cancer simulated population model for incidence and natural history; COL: Colonoscopies; LYG: Life-years gained; DA: Deaths averted; COL 10y: Colonoscopy at a 10-year interval; FIT: Fecal immunological test.

Table 5 Burdens, harms, benefits, and efficiencies for fecal immunological technique and fecal occult blood testing at 3-year adherence rates compared to recommended intervals for colonoscopy and mt-sDNA, ages 50-75, per 1000 people screened

		Burdens and harms			Benefits
CISNETmodel	Test	Stool tests	Total COL	Complications	LYG	CRC DA	CRC incidence reduction	CRC mortality reduction	% of COL 10y LYG	COL per LYG	Complications per LYG	Complications per DA
SimCRC	COL 10y	0	4007	14	275	24	81%	87%	100%	15	0.051	0.58
	FIT3y	6887	971	6	212	18	45%	65%	77%	5	0.028	0.33
	hsFOBT3y	6456	1286	7	212	18	47%	66%	77%	6	0.033	0.39
	mt-sDNA3y	5990	1701	9	250	22	63%	78%	91%	7	0.036	0.41
MISCAN	COL 10y	0	4101	15	248	22	62%	79%	100%	17	0.060	0.68
	FIT3y	6795	995	7	176	15	28%	55%	71%	6	0.040	0.47
	hsFOBT3y	6302	1296	8	175	15	30%	55%	71%	7	0.046	0.53
	mt-sDNA3y	5779	1714	9	215	19	43%	68%	87%	8	0.042	0.49
CRC-SPIN	COL 10y	0	4049	15	270	24	88%	90%	100%	15	0.056	0.62
	FIT3y	6857	1081	7	178	16	49%	59%	66%	6	0.039	0.44
	hsFOBT3y	6498	1317	8	183	16	53%	61%	68%	7	0.044	0.50
	mt-sDNA3y	5927	1827	10	226	20	68%	76%	84%	8	0.044	0.50

CISNET: National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network; COL: Colonoscopies; COL 10y: Colonoscopy at a 10-year interval; LYG: Life-years gained; CRC: Colorectal cancer; MISCAN: Microsimulation screening analysis; CRC-SPIN: Colorectal cancer simulated population model for incidence and natural history; SimCRC: Simulation model of colorectal cancer; DA: Deaths averted; FIT: Fecal immunological test.