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original article
A bs t r ac t
Background
Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for
colorectal-cancer screening in the average-risk population.
Methods
The rate of participation was higher in the FIT group than in the colonoscopy group
(34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the
colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95%
confidence interval [CI], 0.61 to 1.64; P = 0.99). Advanced adenomas were detected
in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT
group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas
were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects
(0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001).
Conclusions
Subjects in the FIT group were more likely to participate in screening than were those
in the colonoscopy group. On the baseline screening examination, the numbers of
subjects in whom colorectal cancer was detected were similar in the two study
groups, but more adenomas were identified in the colonoscopy group. (Funded by
Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT00906997.)
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Me thods
Study Design
We conducted this randomized, controlled, noninferiority trial in eight Spanish regions (Aragn,
Basque Country, Canarias, Catalonia, Galicia, Madrid, Murcia, and Valencia) with the participation of
15 tertiary care hospitals. The study was designed
to assess the efficacy of one-time colonoscopy and
biennial FIT for reducing the rate of death from
colorectal cancer at 10 years (primary trial outcome). The study started in November 2008 with an
informative nationwide campaign.22 The recruitment period was initiated in June 2009, and the first
round finished in June 2011. Ten-year follow-up
will be completed in 2021.
The study protocol (available with the full text
of this article at NEJM.org) was approved by the
ethics committee at each hospital, and all subjects
provided written informed consent.
Study Population
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Randomization
Study Oversight
Palex Medical and Biogen Diagnstica donated supplies and automated fecal occult-blood analyzers
used for FIT but provided no other support for the
study. The companies were not involved in the design of the study, in the analysis or interpretation of
the data, or in the preparation of the manuscript.
Study Interventions
Statistical Analysis
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R e sult s
Study Population
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76 Completed colonoscopy
Results:
4 CRC
32 Advanced adenomas
9 Nonadvanced adenomas
Results:
26 CRC
482 Advanced adenomas
1100 Nonadvanced adenomas
Results:
32 CRC
220 Advanced adenomas
103 Nonadvanced adenomas
Results:
1 CRC
11 Advanced adenomas
16 Nonadvanced adenomas
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Table 1. Diagnostic Yield of Colonoscopy and Fecal Immunochemical Testing (FIT), According to the Intention-to-Screen
Analysis.*
Colonoscopy
(N = 26,703)
Colorectal Lesion
Cancer
Advanced adenoma
Advanced neoplasia
FIT
(N = 26,599)
Subjects
Rate
Subjects
Rate
no.
no.
Odds Ratio
(95% CI)
P Value
30
0.1
33
0.1
0.99 (0.611.64)
0.99
514
1.9
231
0.9
2.30 (1.972.69)
<0.001
544
2.0
264
1.0
2.14 (1.852.49)
<0.001
Nonadvanced adenoma
1109
4.2
119
0.4
9.80 (8.1011.85)
<0.001
Any neoplasia
1653
6.2
383
1.4
4.67 (4.175.24)
<0.001
* The diagnostic yield was calculated as the number of subjects with true positive results divided by the number of subjects who were eligible to undergo testing. Subjects were classified according to the most advanced lesion.
Odds ratios were adjusted for age, sex, and participating center. CI denotes confidence interval.
Advanced adenoma was defined as an adenoma measuring 10 mm or more in diameter, with villous architecture
(>25%), high-grade dysplasia, or intramucosal carcinoma.
Advanced neoplasia was defined as advanced adenoma or cancer.
Discussion
In this trial, participation rates were low in both
groups of subjects who were invited to undergo
colorectal-cancer screening, but subjects in the FIT
group were more likely to agree to participate than
those in the colonoscopy group. The number of patients in whom colorectal cancer was detected was
similar in the two study groups, but more patients
with adenomas were identified in the colonoscopy
group. Since the primary outcome of this trial is the
reduction in the rate of death from colorectal can702
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Table 2. Diagnostic Yield of Colonoscopy and Fecal Immunochemical Testing (FIT), According to the Intention-to-Screen
Analysis and the Location of the Colorectal Lesion.*
Colorectal Lesion
Colonoscopy
(N = 26,703)
FIT
(N = 26,599)
Odds Ratio
(95% CI)
P Value
Subjects
Rate
Subjects
Rate
no.
no.
<0.1
11
<0.1
0.56 (0.211.53)
0.26
25
0.1
23
0.1
1.22 (0.692.16)
0.49
Proximal
199
0.7
51
0.2
4.06 (2.985.53)
<0.001
Distal
365
1.4
206
0.8
1.82 (1.532.16)
<0.001
Proximal
205
0.8
62
0.2
3.44 (2.584.57)
<0.001
Distal
390
1.5
229
0.9
1.76 (1.492.08)
<0.001
Proximal
608
2.3
62
0.2
10.06 (7.7413.08)
<0.001
Distal
677
2.5
85
0.3
8.21 (6.5510.29)
<0.001
813
3.0
124
0.5
6.84 (5.658.27)
<0.001
1067
4.0
314
1.2
3.58 (3.154.07)
<0.001
Cancer
Proximal
Distal
Advanced adenoma
Advanced neoplasia
Nonadvanced adenoma
Any neoplasia
Proximal
Distal
* The diagnostic yield was calculated as the number of subjects with true positive results divided by the number of subjects who were eligible to undergo testing. Subjects were classified according to the most advanced lesion that was
proximal or distal to the splenic flexure. The total number of subjects with proximal and distal lesions may exceed the
total number of subjects because subjects could have lesions in both locations.
Odds ratios were adjusted for age, sex, and participating center.
Advanced adenoma was defined as an adenoma measuring 10 mm or more in diameter, with villous architecture
(>25%), high-grade dysplasia, or intramucosal carcinoma.
Advanced neoplasia was defined as either advanced adenoma or cancer.
is that one-time screening with FIT was very similar to one-time colonoscopy with respect to the rate
of detection of colorectal cancer, and there was no
significant difference in the stage of tumors detected by the two strategies. Additional cases of
colorectal cancer might be detected during ongoing biennial FIT screening, and this could lead to
an increased rate of cancer detection and a decreased rate of death in this group. On the other
hand, more tumors might have been prevented in
the colonoscopy group owing to the larger number
of adenomas detected and removed, in comparison
with the FIT group.
The higher detection rate and diagnostic yield
of colonoscopy with respect to premalignant lesions also warrant comment. First, since advanced
adenomas are usually considered a surrogate
marker for colorectal cancer,32,33 the superiority of
colonoscopy for detecting such lesions should be
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Table 3. Detection Rate for Colonoscopy and Fecal Immunochemical Testing (FIT), According to the As-Screened
Analysis.*
Colorectal Lesion
Cancer
Colonoscopy
(N = 5059)
FIT
(N = 10,507)
Odds Ratio
(95% CI)
P Value
Subjects
Rate
Subjects
Rate
no.
no.
27
0.5
36
0.3
1.56 (0.932.56)
0.09
Advanced adenoma
493
9.7
252
2.4
4.32 (3.695.07)
<0.001
Advanced neoplasia
520
10.3
288
2.7
4.01 (3.454.67)
<0.001
Nonadvanced adenoma
1116
22.1
112
1.1
25.98 (21.2731.74)
<0.001
Any neoplasia
1636
32.3
400
3.8
12.28 (10.8913.84)
<0.001
* The detection rate is the comparison between the number of positive results and the number of subjects who actually
underwent testing. Subjects were classified according to the most advanced lesion.
A total of 104 subjects with positive results on FIT did not undergo colonoscopy.
Odds ratios were adjusted according to age, sex, and participating center.
Advanced adenoma was defined as an adenoma measuring 10 mm or more in diameter, with villous architecture
(>25%), high-grade dysplasia, or intramucosal carcinoma.
Advanced neoplasia was defined as advanced adenoma or cancer.
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