Diagnosis reliability of combined flexible sigmoidoscopy and fecal-immunochemical test in colorectal neoplasia screening

Figures & data

Figure 1 Study flow diagram. Arm (A) includes the individuals referred for FIT and subsequent colonoscopy; the arm (B) subsample consists of the individuals who additionally underwent real sigmoidoscopy.

Abbreviations: FIT, fecal-immunochemical test; IC, informed consent.

Figure 2 Scheme for testing combination.

Notes: The first stage consists of the parallel combination (notation #) of two diagnostic tests. The second stage is a serial combination (notation ~) of the previous stage result and a third reference (gold standard) test. T(±) denotes the final decision in the screening process.
Abbreviations: COL, colonoscopy; FIT, fecal-immunochemical test; SIG, sigmoidoscopy.

Table 1 Characteristics of individuals included in the evaluation of diagnosis reliability

Characteristics of the patients	Number (N=252)
Age (years)	63.65±8.781a
Sex (female)	144 (57.1%)
Urban (yes)	175 (69.4%)
Colorectal cancer (yes)	45 (17.85%)
Distal to splenic flexure	24 (9.52%)
Proximal to splenic flexure	16 (6.35%)
Distal and proximal to splenic flexure	5 (1.98%)
Advanced neoplasia (yes)	75 (29.76%)
Distal to splenic flexure	39 (15.48%)
Proximal to splenic flexure	26 (10.32%)
Distal and proximal to splenic flexure	10 (3.97%)
Advanced adenoma (yes)	30 (10.37%)
Distal to splenic flexure	15 (3.97%)
Proximal to splenic flexure	10 (2.52%)
Distal and proximal to splenic flexure	5 (1.98%)
Nonadvanced adenoma (yes)	57 (22.62%)
Proximal to splenic flexure	23 (9.13%)
Distal and proximal to splenic flexure	10 (3.97%)

Note:

a Mean ± standard deviation.

Table 2 Diagnostic performance of the different testing approaches

Diagnosis method	Positives	Negatives	Sensitivity (%)a	Sensitivity (95% CI)	Specificity (%)a	Specificity (95% CI)
Colonoscopy	75	177	Reference test
A. FIT for advanced and non-advanced neoplasia detection (N =252)
AN	91	104	72	(60.44, 81.76)	69.17	(60.09, 77.27)
Proximal AN	64	92	75	(57.8, 92.21)	69.17	(60.09, 77.27)
Distal AN	70	99	67.35	(52.46, 80.05)	69.17	(60.09, 77.27)
Non-AA	50	127	23.81	(8.22, 47.17)	71.15	(63.37, 78.12)
B. Simulating sigmoidoscopy strategies for advanced neoplasia detection (N =252)
USPLCOb	58	137	68	(56.22, 78.31)	94.17	(88.35, 97.62)
UKb	56	139	57.33	(45.38, 68.69)	89.17	(82.19, 94.1)
SCOREb	60	135	62.67	(50.73, 73.57)	89.17	(82.19, 94.1)
NORCCAPb	66	137	66.67	(54.83, 77.14)	93.33	(87.29, 97.08)
C. Comparison of real and simulated sigmoidoscopy, on a sub-sample (N =57)
Real SIG	7	35	40.74	(19.92, 65.11)	93.33	(73.47, 97.89)
USPLCOb	7	35	41.67	(15.17, 72.33)c	93.33	(77.93, 99.18)c
UKb	6	36	25	(5.49, 57.19)c	90	(73.47, 97.89)c
SCOREb	7	35	25	(5.49, 57.19)c	86.67	(69.28, 96.24)c
NORCCAPb	9	33	41.67	(15.17, 72.33)c	86.67	(69.28, 96.24)c

Notes: Colonoscopy was the reference test for FIT and for the simulating sigmoidoscopy strategies. Methods for simulation: USA PLCO trial;⁵ UK flexible sigmoidoscopy trial;⁶ SCORE trial;⁷ NORCCAP trial.⁸

a Values are expressed as point estimates and 95% CIs.

b Rectum, sigmoid, and descending colon were considered for sigmoidoscopy simulation.

c Exact McNemar test did not reject the null hypothesis when compared with Real SIGmoidoscopy.

Abbreviations: AA, advanced adenoma; AN, advanced neoplasia; CI, confidence interval; FIT, fecal-immunochemical test.

Table 3 Parallel combination of FIT and sigmoidoscopy, as the first stage of the screening scheme proposed (N=252)

Combination	Positives	Negatives	Sensitivitya (%)	Sensitivity (95% CI)	P-valueb	Specificitya (%)	Specificity (95% CI)
FIT#USPLCOc	110	85	96	(88.75, 99.17)	<0.001	68.33	(59.22, 76.52)
FIT#UKc	105	90	89.33	(80.06, 95.28)	<0.001	68.33	(59.22, 76.52)
FIT#SCOREc	106	89	90.67	(81.71, 96.16)	<0.001	68.33	(59.22, 76.52)
FIT#NORCCAPc	107	88	93.33	(85.12, 97.8)	<0.001	69.17	(60.09, 77.27)

Notes: Simulated sigmoidoscopy was performed based on colonoscopy. Methods for simulation: USA PLCO trial;⁵ UK flexible sigmoidoscopy trial;⁶ SCORE trial;⁷ NORCCAP trial.⁸

a Values are expressed as point estimates and 95% CIs.

b Significance of combination sensitivity when compared with sigmoidoscopy alone (McNemar test).

c Rectum, sigmoid, and descending colon were considered for sigmoidoscopy simulation.

Abbreviations: CI, confidence interval; FIT, fecal-immunochemical test.

Figure 3 First stage calculated predictive values versus prevalence: FIT (left), SIG (middle), and SIG with FIT#SIG combined test (right).

Notes: The red color text refers to the red color curves. Solid line was used for PVP and dotted line for PVN.
Abbreviations: COL, colonoscopy; FIT, fecal-immunochemical test; SIG, sigmoidoscopy; PVP, predictive value positive; PVN, predictive value negative.

Figure 4 Second stage calculated predictive values versus prevalence: FIT#SIG combined test (left), COL (middle), and COL with FIT#SIG~COL combined test (right).

Notes: The red color text refers to the red color curves. Solid line was used for PVP and dotted line for PVN.
Abbreviations: COL, colonoscopy; FIT, fecal-immunochemical test; SIG, sigmoidoscopy; PVP, predictive value positive; PVN, predictive value negative.

Table 4 Predictive values of FIT#SIG~COL screening strategy for colorectal neoplasia detection

FIT#SIG~COL	PV positivea (%)	PV positive (95% CI)	PV negativea (%)	PV negative (95% CI)
Actual – arm (B)	36.36	(23.87, 48.84)	84.61	(75.24, 93.98)
Calculated – arm (A)b	40.57	(34.51, 46.63)	85.81	(81.5, 90.12)

Notes: Calculated and actual values in the study sample are provided. Arms (A) and (B) are the two arms of the study.

a Values are expressed as point estimates and 95% CIs.

b Rectum, sigmoid, and descending colon were considered for UK-criteria⁶ sigmoidoscopy simulation.

Abbreviations: COL, colonoscopy; CI, confidence interval; FIT, fecal-immunochemical test; PV, predictive value; SIG, sigmoidoscopy.

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