Fecal occult blood versus DNA testing: indirect comparison in a colorectal cancer screening population

Figures & data

Table 1 Recruitment and characteristics of study population in the BLITZ sample evaluating FOB Gold compared to the MSDT study evaluating Cologuard⁷

Recruitment		MSDT study evaluation of Cologuard^Citation7		BLITZ study evaluation of FOB Gold^®
		June 2011–November 2012, private practices and academic centers in the US and Canada		November 2008–September 2014, private practices in Germany
Characteristics of study population		n	%	n	%
Sex	Male	4625	46.3	1737	49.7
	Female	5364	53.7	1757	50.3
Age, years	50–54	2862	28.7	98	2.8
	55–59			1514	43.3
	60–64	819	8.2	735	21.0
	65–69	3670	36.7	535	15.3
	70–74	1735	17.4	447	12.8
	75–84	903	9.0	165	4.7
Most advanced finding at screening colonoscopy	CRC	65	0.65	30	0.86
	Stage I	29	0.29	10	0.29
	Stage II	21	0.21	4	0.11
	Stage III	10	0.10	13	0.37
	Stage IV	4	0.04	3	0.09
	APCL#	757	7.58	359	10.27
	≥1 cm	691	6.92	276	7.90
	<1 cm	66	0.66	83	2.37
	Non-advanced adenoma	2893	28.96	688	19.69
	None of the above	6274	62.81	2417	69.18

Note:

# APCLs, including advanced adenomas and sessile serrated polyps ≥1 cm.

Abbreviations: MSDT, multitarget stool DNA test; CRC, colorectal cancer; APCL, advanced precancerous lesion.

Table 2 Comparison of diagnostic performance of Cologuard in the MSDT study⁷ and of FOB Gold in the BLITZ study

Most advanced finding at screening colonoscopy*	Cologuard, MSDT study^Citation7			FOB Gold, BLITZ study
				Ntotal	Original cutoff				Adjusted cutoff
	Ntotal	Npos	Indicator % (95% CI)		Npos	Indicator % (95% CI)	Difference* % (95% CI)	p-value*	Npos	Indicator % (95% CI)	Difference* % (95% CI)	p-value*
			Sensitivity			Sensitivity				Sensitivity
CRC, any stage	65	60	92.3 (83.0 to 97.5)	30	29	96.7 (82.8 to 99.9)	4.4 (−9.7 to 13.9)	0.66	29	96.7 (82.8 to 99.9)	4.4 (−9.7 to 13.9)	0.66
CRC stages I–III	60	56	93.3 (83.8 to 98.2)	27	26	96.3 (81.0 to 99.9)	3.0 (−12.2 to 12.7)	1.00	26	96.3 (81.0 to 99.9)	3.0 (−12.2 to 12.7)	1.00
APCL	757	321	42.4 (38.9 to 46.0)	359	121	33.7 (28.8 to 38.9)	−8.7 (−14.6 to −2.6)	0.006	170	47.4 (42.1 to 52.7)	5.0 (−1.3 to 11.2)	0.12
≥1 cm	691	301	43.6 (39.8 to 47.4)	276	110	39.9 (34.0 to 45.9)	−3.7 (−10.4 to 3.2)	0.31	150	54.3 (48.3 to 60.3)	10.8 (3.8 to 17.6)	0.003
<1 cm	66	20	30.3 (19.6 to 42.9)	83	11	13.3 (6.8 to 22.5)	−17.1 (−30.3 to −3.8)	0.01	20	24.1 (15.4 to 34.7)	−6.2 (−20.5 to 7.9)	0.46
Non-advanced adenoma	2893	498	17.2 (15.9 to 18.6)	688	69	10.0 (7.9 to 12.5)	−7.2 (−9.7 to −4.4)	<0.001	134	19.5 (16.6 to 22.6)	2.3 (−0.9 to 5.7)	0.16
CRC or high-grade dysplasia	104	87	83.7 (75.1 to 90.2)	60	44	73.3 (60.3 to 83.9)	−10.3 (−24.0 to 2.3)	0.16	47	78.3 (65.8 to 87.9)	−5.3 (−18.6 to 6.6)	0.41
CRC or APCL ≥1 cm	756	361	47.8 (44.1 to 51.4)	306	139	45.4 (39.8 to 51.2)	−2.3 (−8.9 to 4.3)	0.50	179	58.5 (52.8 to 64.1)	10.8 (4.1 to 17.2)	0.002
CRC or any APCL	822	381	46.4 (42.9 to 49.8)	389	150	38.6 (33.7 to 43.6)	−7.8 (−13.6 to −1.8)	0.01	199	51.1 (46.1 to 56.2)	4.8 (−1.2 to 10.8)	0.12
			Specificity			Specificity				Specificity
No CRC or APCL	9167	1231	86.6 (85.9 to 87.2)	3105	225	92.8 (91.8 to 93.6)	6.2 (5.0 to 7.3)	<0.001	419	86.5 (85.3 to 87.7)	−0.1 (−1.5 to 1.3)	0.93

Notes: Results for FOB Gold are derived for the original cutoff given by the manufacturer (17 µg hb/g feces) and for an adjusted cutoff (8.4 µg hb/g feces) yielding the same specificity with respect to advanced neoplasms (86.6%) as reported for Cologuard. APCL including advanced adenomas and sessile serrated polyps ≥1 cm.

* Differences and p-values refer to comparison with Cologuard.⁷ p≤0.05 are in bold.

Abbreviations: MSDT, multitarget stool DNA test; APCL, advanced precancerous lesion; CRC, colorectal cancer; N_pos, number of positive results.

Figure 1 Sensitivity for detecting CRC and APCL ≥1 cm and specificity of FOB Gold (using the original cutoff) compared to Cologuard in the MSDT study (data derived from Imperiale et al),⁷ with and without age adjustment of FOB Gold results to age distribution of MSDT study population: FIT-O, FOB Gold using original cutoff, no age adjustment; FIT-A, FOB Gold using original cutoff, age adjusted.

Abbreviations: CRC, colorectal cancer; APCL, advanced precancerous lesion; MSDT, multitarget stool DNA test; FIT, fecal immunochemical test.

Table 3 Comparison of site-specific sensitivity of Cologuard in the MSDT study⁷ and of FOB Gold in the BLITZ study

Most advanced finding at screening colonoscopy*	Cologuard, MSDT study^Citation7			FOB Gold, BLITZ study
				Ntotal	Original cutoff				Adjusted cutoff
	Ntotal	Npos	Sensitivity % (95% CI)		Npos	Sensitivity % (95% CI)	Difference^ % (95% CI)	p-value^	Npos	Sensitivity % (95% CI)	Difference^ % (95% CI)	p-value^
Proximal CRC	30	27	90.0 (73.4 to 97.9)	5	5	100 (47.8 to 100)	10.0 (−33.9 to 25.6)	1.00	5	100 (47.8–100)	10.0 (−33.9 to 25.6)	1.00
Proximal APCL	431	143	33.2 (28.8 to 37.8)	141	28	19.9 (13.6 to 27.4)	−13.3 (−20.7 to −4.8)	0.001	53	37.6 (29.6 to 46.1)	4.4 (−4.4 to 13.7)	0.36
Proximal CRC or APCL	461	170	36.9 (32.5 to 41.5)	146	33	22.6 (16.1 to 30.3)	−14.3 (−21.8 to −5.7)	0.001	58	39.7 (31.7 to 48.1)	2.9 (−6.0 to 12.0)	0.56
Distal CRC	35	33	94.3 (80.8 to 99.3)	25	24	96.9 (79.6 to 99.9)	1.7 (−14.4 to 15.0)	1.00	24	96.9 (79.6 to 99.9)	1.7 (−14.4 to 15.0)	1.0
Distal APCL	325	177	54.5 (48.9 to 60.0)	236	104	44.1 (37.6 to 50.7)	−10.4 (−18.6 to −2.0)	0.017	132	55.9 (49.3 to 62.4)	1.5 (−6.8 to 9.7)	0.73
Distal CRC or APCL	360	210	58.3 (53.1 to 63.5)	261	128	49.0 (42.8 to 55.3)	−9.3 (−17.1 to −1.4)	0.023	156	59.8 (53.5 to 65.8)	1.4 (−6.4 to 9.2)	0.74

Notes: Results for FOB Gold are derived for the original cutoff given by the manufacturer (17 µg hb/g feces) and for an adjusted cutoff (8.4 µg hb/g feces) yielding the same specificity with respect to advanced neoplasms (86.6%) as reported for Cologuard. APCL including advanced adenomas and sessile serrated polyps ≥1 cm; N_pos, number of positive results.

* Participants with the respective most advanced finding in both the proximal colon and distal colon or rectum were included in site-specific analyses for both sites.

^ Differences and p-values refer to comparison with Cologuard.⁷ p≤0.05 are in bold.

Abbreviations: MSDT, multitarget stool DNA test; APCL, advanced precancerous lesion; CRC, colorectal cancer; N_pos, number of positive results.

ImperialeTFRansohoffDFItzkowitzSHMultitarget stool DNA testing for colorectal-cancer screeningN Engl J Med2014370141287129724645800

 PubMed Web of Science ®Google Scholar