Introduction
Colorectal cancer (CRC) is currently the third most incident cancer worldwide and
the second highest cause of cancer-related death [1 ]. Fecal occult blood test (FOBT)-based population screening programs are aimed at
reducing the CRC mortality [2 ]
[3 ] based on the selection of those asymptomatic individuals with a higher risk of having
advanced adenomas (≥ 10 mm, villous component or high grade dysplasia) or cancer,
to subsequently undergo colonoscopy. Several population-based studies have demonstrated
an important reduction in long-term risk of CRC and mortality after a colonoscopy
[4 ]
[5 ]. However, the colonoscopy is not faultless. CRC still occurs after a negative colonoscopy
and before the recommended surveillance [6 ]
[7 ], the so-called colonoscopy interval CRC [8 ].
Fecal immunochemical tests (FIT) are immunoassays specific for intact human hemoglobin
[9 ], recommended as first choice over guaiac-FOBT given their higher specificity for
human blood superiority and better sensitivity for the detection of advanced colorectal
neoplasia [10 ]. In the scenario of organized FIT-based screening programs, around 20 – 30 % of
individuals have a positive test followed by a negative colonoscopy [11 ]. These individuals are considered at null risk for CRC for the following 10 years
[12 ]. However, it is well known that about 20 % of colorectal adenomas are missed at
colonoscopy [13 ] and that the adenoma detection rate of the endoscopist is inversely related to the
incidence of interval CRC [14 ]. The recommendation of a 10-year interval without screening in those individuals
with a false positive result may create a concern among endoscopists worried about
the possibility of having missed a significant lesion. The incidence of CRC after
a positive FIT and negative colonoscopy has not been reported until now.
In the context of an organized FIT-based CRC screening program, we aimed to assess
the cumulative incidence of CRC in individuals with positive FIT followed by a negative
colonoscopy. Secondly, we aimed to identify other lesions that could explain the test
positivity in this cohort.
Patients and methods
This observational study was carried out within a FIT-based organized population CRC
Screening Program, in which all individuals aged 50 – 69 were invited to participate.
Personal history of CRC, adenoma, or inflammatory bowel disease, a family history
of hereditary or familial CRC (defined as those individuals with two first-degree
relatives with CRC or one diagnosed before the age of 60), severe coexisting illness,
colonoscopy performed within the last 5 years, previous colectomy, or a contraindication
for colonoscopy were considered exclusion criteria for screening. In the present study,
we included all individuals living in the referral area of the Hospital Clinic of
Barcelona who participated in the first round of the screening program (from January
2010 to December 2012) and had a positive FIT result followed by a complete negative
colonoscopy defined as the absence of CRC, adenomas or serrated polyps (excluding
hyperplastic polyps ≤ 5 mm in the sigmoid colon or rectum).
Study setting and data collection
The FIT-based screening program consisted of a single stool sample analysis using
the automated semi-quantitative OC-Sensor (Eiken Chemical, Japan), without specific
dietetic or medical treatment restrictions. Participants were always warned that if
menstruation, hemorrhoid or fissure bleeding were present, the stool sample collection
must be postponed until after 3 days without macroscopic bleeding. Positive FIT was
defined as a cutoff of ≥ 20 μg of hemoglobin/mg of feces. Once a positive FIT-result
was obtained, the colonoscopy was performed within 1 to 2 months.
For bowel preparation, all patients were encouraged to adhere to a low-fiber/fat diet
3 days before the colonoscopy and bowel cleansing was carried out with 4 L of polyethylene
glycol and electrolyte lavage solution (Solución Evacuante Bohm, Laboratorios Bohm
S.A., Fuenlabrada, Madrid, Spain) in split-dose [15 ]. For patients with previous inadequate preparation, sodium picosulfate magnesium
oxide and citric acid (CitraFleet, Casen-Fleet, Zaragoza, Spain) were added to Bohm
for intensive bowel cleansing.
All colonoscopies were performed in the Hospital Clinic of Barcelona, a tertiary academic
center that follows high quality standards [16 ], by 12 experienced endoscopists each having performed more than 400 colonoscopies
per year and with a known high adenoma detection rate (i. e. 29.8 % in primary colonoscopy
screening and 47.1 % in FIT-based screening) [17 ]
[18 ]. Procedures were performed under spontaneous breathing deep sedation (propofol and
remifentanil infusion) administered by trained nurses supervised by anesthesiologists
in 40-minute time slots. Standard definition (CF-Q160 L/CF-Q165L; EVIS EXERA II processor;
Olympus, Tokyo, Japan) or high definition (CF-H180AL/CF-HQ190L; EVIS EXERA III processor;
Olympus, Tokyo, Japan) white-light endoscopes were used. Bowel cleansing was considered
adequate (excellent or good) if Boston score was ≥ 6 points (≥ 2 by colonic segment).
Examination was considered completed if cecal intubation was reached and a minimum
of 6 minutes of withdrawal time was normally advised.
Colonoscopies and their respective pathology reports were reviewed weekly by a committee
composed of expert gastroenterologists, endoscopists, and nurses before follow-up
recommendations were dictated. In cases of inadequate bowel preparation or incomplete
procedure, colonoscopies were rescheduled as necessary until an optimal examination
(i. e. complete with adequate colonic preparation) was achieved.
Participants’ baseline data were prospectively recorded in the CRC screening program
database. Demographics, comorbidities, chronic treatment, FIT levels, and index colonoscopy
findings were obtained from both the CRC screening program database and hospital medical
records. From each individual included, we investigated the hospital’s medical records
and Catalonia’s National Health Service database in order to find any medical consultation
due to gastrointestinal disorders after the index colonoscopy. The latest mentioned
database registers only those patients who require hospitalization and/or complementary
tests in public health centers other than Catalonia. When reliable information was
lacking or absent (e. g. individuals attended private health care centers or those
moving out of Catalonia), a brief structured telephonic interview was performed. This
study was approved by the Ethic and Clinic Investigation Committee from Hospital Clinic
of Barcelona. All individuals provided informed consent to participate in the CRC
screening program and to collect their personal data on the program’s database. All
individuals interviewed by telephone provided a recorded informed consent.
Definitions and study outcomes
Post-colonoscopy CRC (PCCRC) was defined as those tumors that invade the submucosa
layer or beyond [8 ] detected after the (index) negative colonoscopy until the end of study follow-up. The
incidence of PCCRC was expressed as cumulative incidence, defined as the proportion
of PCCRC diagnosed during the observation time (cases/all individuals with negative
colonoscopy*100) expressed as a percentage. Also the cumulative rate of PCCRC was
calculated by dividing the cases of PCCRC by the sum of the observation time (average
in years) of the individuals with negative colonoscopy (“at risk”) expressed as cases/person-years.
We also calculated the rate of PCCRC as the proportion of “new” cancers among the
total number of cancers detected in the index colonoscopy cohort [8 ].
At baseline, negative colonoscopies were categorized into colonoscopy with potentially
bleeding lesions (those with a high chance of producing occult or macroscopic bleeding,
such as angiodysplasia, radiation proctitis, ulcers, etc.) and normal colonoscopy
(no lesions or lesions of almost null probability of bleeding, such as non-complicated
diverticulosis, left side-located small hyperplastic polyps, and hemorrhoids without
stigmata of recent hemorrhage).
At follow-up, a relevant lesion was defined as any neoplastic or non-neoplastic lesion
throughout the gastrointestinal tract that could reasonably produce a macroscopic
or occult bleeding. Definitions were established by author consensus prior to data
acquisition, i. e. erosive esophagitis Los Angeles’s grade B or more, CRC, adenomas,
ileal ulcers or gastro-duodenal peptic ulcers were considered to be relevant lesions
while a mild gastritis or non-complicated hiatus hernia were not.
Disorders such as Child – Pugh C stage hepatic cirrhosis, advanced (stage IV or V)
renal disease, thrombocytopenia or coagulation disorders were considered to be pro-hemorrhagic
comorbidities. Chronic non-steroidal anti-inflammatory drug (NSAID) use was defined
as daily consumption during ≥ 1 month within the 2 months before the fecal sampling.
Statistical analysis
Continuous variables with a normal distribution were reported as mean (standard deviation)
and compared using the Student’s t test. Continuous variables with a skewed distribution were reported as median (interquartile
range, IQR) and compared using the Mann-Whitney U test. Frequencies (%) were used to report categorical variables, which were compared
using the Chi-squared test or Fischer’s exact test when corresponding. All statistical
tests were two-sided, and P values < 0.05 were considered to be statistically significant. Multiple logistic
regression was used to identify independent predictors of PCCRC and relevant lesions
using backward stepwise variable selection. All variables in the univariable analysis
were included in the model. Odds ratios (ORs) and associated 95 % confidence intervals
(CIs) were used to quantify the level of association. IBM SPSS Statistics for Windows,
Version 23.0 (IBM Corp., Armonk, NY, United States) was used to analyze the data.
Results
A total of 130 206 individuals (female 54.2 %; age 58.4 ± 0.03 years) were invited
to the first screening round and 52 731 (40.5 %) returned the FIT. Of them, 3065 (5.8 %)
individuals had a positive result and 2659 (86.7 %) underwent colonoscopy. According
to the result of this index colonoscopy, 179 (6.7 %) individuals presented CRC, 1637
(61.6 %) presented adenomas and 811 (30.5 %) (female 60.7 %; age 59.1 ± 5.6) had a
negative colonoscopy. Out of 811 individuals with negative colonoscopy, 102 (12.6 %)
had potentially bleeding lesions and the remaining 709 had a normal colonoscopy. [Table 1 ] depicts the baseline characteristics of these individuals. Individuals with potentially
bleeding lesions were slightly older with a higher proportion of men (62.8 %) and
chronic NSAIDs consumers than those with normal colonoscopy. As expected, these individuals
had higher hemoglobin concentrations in feces than those with normal colonoscopy ([Table 1 ]).
Table 1
Baseline characteristics for the 811 individuals with negative colonoscopy.
Normal colonoscopy (n = 709)
Potentially bleeding lesions (n = 102)
P value
Age (standard deviation), years
58.9 (5.6)
60.4 (5.2)
0.012
Gender: female (%)
445 (62.8)
47 (46.1)
0.001
FIT, median (IQR), μg Hb/g feces
47.0 (79.8)
72.9 (208.7)
0.004
Pro-hemorrhagic comorbidities (%)
7 (1.0)
1 (1.0)
0.995
3 (0.4)
0
–
3 (0.4)
0
–
1 (0.1)
1 (1.0)
0.236
Concomitant therapy (%)
73 (10.3)
17 (16.7)
0.056
56 (7.9)
10 (9.8)
0.513
11 (1.6)
1 (1.0)
0.654
6 (0.8)
6 (5.9)
0.002
FIT, fecal immunochemical test; IQR, interquartile range; NSAIDs, non-steroidal anti-inflammatory
drugs.
As is shown in [Fig. 1 ] a complete follow-up was available in 740 (91 %) of the individuals with negative
colonoscopy with an average observation time of 4.7 years (range, 3.5 – 6.3 years).
[Fig. 2 ] summarizes the outcomes for the 811 individuals with negative colonoscopy.
Fig. 1 Flow chart of data acquisition for the 811 individuals with negative colonoscopy.
Fig. 2 Outcomes for the 811 individuals with negative colonoscopy.
Incidence of PCCRC
Three out of 740 individuals developed PCCRC (age, 56.3 ± 7.5 years; 66 % men) at
11, 27, and 28 months after the negative colonoscopy ([Fig. 2 ]), resulting in a cumulative incidence of 0.4 % and an incidence rate of 0.8/1000
person-years. Furthermore, the rate of PCCRC among the total number of cancers detected
in the cohort who underwent the index colonoscopy was 1.65 % (3/182).
All tumors were TNM stage III, had normal expression of mismatch repair proteins at
immunohistochemistry, and had no microsatellite instability. The patient who developed
PCCRC at 11 months had a polypoid lesion of 15 mm in the ascending colon, whereas
the other two individuals had larger tumors in the sigmoid colon and rectum. None
of these three patients had synchronous neoplastic lesions. Regarding index colonoscopies,
all were reported as complete with an adequate bowel preparation. Unfortunately, an
exhaustive post-hoc revision of the index colonoscopy was not possible since screening
colonoscopies were not systematically video recorded. Details of the three individuals
with PCCRC are shown in [Table 2 ]. There were no statistically significant differences with regard to age, gender,
FIT level, comorbidities, and chronic use of antiplatelets/anticoagulants or NSAIDs
among individuals with or without PCCRC (data not shown).
Table 2
Characteristics of the three individuals with PCCRC.
Patient 1
Patient 2
Patient 3
General characteristics
Female
Male
Male
65
53
51
68
44
90.6
Index colonoscopy
Normal
Distal diminutive hyperplastic polyps and diverticulosis
Normal
Excellent
Good
Good
Subsequent colonoscopy
11
27
28
Change in bowel habits
Rectal bleeding
Rectal bleeding
Tumor characteristics
Ascending colon
Sigmoid colon
Rectum
Sessile lesion 15 mm
Stenosing tumor
Flat lesion 40 mm
IIIA = T1 – 2 N1 M0
IIIB = T2 – 3 N2 M0
IIIA = T1 – 2 N1 M0
Low grade
High grade (40 % mucinous component, signet ring cells)
Moderate grade
Normal
Normal
Normal
Microsatellite instability
No
No
No
PCCRC, post-colonoscopy colorectal cancer; FIT, fecal immunochemical test; MMR, mismatch
repair (MLH1, MSH2, MSH6, and PMS2 by immunohistochemistry).
Other findings during follow-up
As shown in [Fig. 2 ], among those 647 individuals with normal index colonoscopy, 70 (11 %) presented
gastrointestinal disorders that required complementary endoscopic procedures. In 32
patients, relevant lesions were detected, of which 11 were located in the upper gastrointestinal
tract and 21 in the terminal ileum or colon – rectum (including the three cases of
PCCRC). The remaining 38 individuals had a normal endoscopic examination.
One-third of relevant lesions (11 out of 32) were significant neoplasias: two (2/647;
0.3 %) located in the upper-medium gastrointestinal tract (gastric cancer and small-bowel
lymphoma, respectively) and nine (9/647; 1.4 %) located in the colon – rectum (6 advanced
adenomas, 3 invasive CRC). The remaining relevant lesions (21 out of 32) were inflammatory,
vascular disorders, or non-advanced colorectal adenomas. Four out of 32 relevant lesions
were diagnosed within the first 6 months: an advanced gastric adenocarcinoma clinically
manifested by hematemesis and melena; a caustic esophageal stricture, with monthly
esophageal dilations due to recurrent dysphagia; an advanced jejunal lymphoma, manifested
by weight loss and intestinal occlusion; and a gastric antral vascular ectasia manifested
by iron-deficiency anemia ([Fig. 2 ]).
Factors such as age, gender, FIT level, and chronic use of antiplatelets or anticoagulants
were not associated with a higher incidence of relevant lesions. However, in the multivariable
analysis, those individuals with either pro-hemorrhagic advanced comorbidities or
chronic use of NSAIDs presented a higher risk of having a relevant lesion (OR 16 [3.5 – 79.1];
P < 0.001 and OR 11 [1.9 – 64.0]; P = 0.006, respectively) ([Table 3 ]). The subsequent relevant lesions in the two NSAID users were ileal aphthous ulcers
and sigmoidal colitis, respectively. A gastric antral vascular ectasia was found in
a patient with advanced hepatic cirrhosis. Finally, a jejunal lymphoma and one advanced
adenoma (in situ carcinoma) were found in two patients with end-stage renal disease
([Table 3 ]).
Table 3
Univariable and multivariable analysis of factors related to subsequent relevant lesion
in individuals with normal colonoscopy.
Normal colonoscopy
No relevant lesion (n = 615)
Relevant lesion (n = 32)
Univariable analysis, OR
P value
Multivariable analysis[1 ], adjusted OR
P value
Age, mean ± standard deviation, years
58.6 ± 5.5
59.3 ± 5.8
–
0.474
–
–
Gender, female (%)
386 (56.3)
18 (56.3)
1.31 (0.64 – 2.68)
0.458
–
–
FIT, median (IQR), μg Hb/g feces
46.4 (29.7 – 112.2)
47.9 (24.4 – 90.3)
–
0.673
–
–
NSAIDs (%)
4 (0.7)
2 (6.3)
10.81 (1.7 – 57.81)
0.031
11.2 (1.9 – 64.0)
0.006
Antiplatelets (%)
44 (7.2)
4 (12.5)
1.85 (0.62 – 5.52)
0.286
–
–
Anticoagulants (%)
11 (1.8)
0
–
–
–
–
Advanced chronic disease (%)
4 (0.7)
3 (9.4)
17.4 (3.7 – 81.3)
0.003
16.8 (3.5 – 79.1)
< 0.001
OR, odds ratio; FIT, fecal immunochemical test; IQR, interquartile range; NSAIDs,
non-steroidal anti-inflammatory drugs.
1 Adjusted by age, sex, and anticoagulant/antiplatelet treatment.
Potentially bleeding lesions at index colonoscopy were considered to be responsible
for the FIT positivity in this group of individuals ([Fig. 2 ]).
Discussion
This observational study reports the outcome of individuals with positive FIT and
negative colonoscopy recruited in an organized, population-based CRC screening program
after an average follow-up period of 4.7 years (range, 3.5 – 6.3 years) and exhaustive
data collection.
Three out of 740 individuals with negative colonoscopy developed PCCRC, resulting
in a cumulative incidence of 0.4 % and an incidence rate of 0.8/1000 person-years.
Furthermore, the rate of PCCRC among the total number of all detected CRC in the cohort
(screen-detected plus PCCRC) was 1.65 % (3/182).
The reported proportions of interval CRC vary greatly, ranging from 0.8 % [19 ] of colonoscopic examinations to up to 9 % [20 ] of all diagnosed CRCs; they are not comparable due to the use of different calculation
methods [7 ]
[8 ]. The incidence proportion of PCCRC/number of colonoscopies could be a more practical
method for assessing the quality of a colonoscopy unit but currently there is not
a standardized method.
The incidence of CRC after a negative colonoscopy in the context of population organized
FOBT-based screening programs has only been reported in two studies that used guaiac-FOBT.
A Danish study reported 14 CRCs out of 771 positive guaiac-FOBT followed by a negative
colonoscopy (1.8 %) after 8 years of follow-up [11 ]. In that study, the individuals with positive FOBT and subsequent negative colonoscopy
had the same long-term CRC risk as individuals with positive FOBT and adenomas and
as the unscreened reference population [11 ]. Based on these results, the authors suggested that a 10-year interval of screening
may not be safe. Another recent study from a Scottish population screening program
reported a lower rate of PCCRC or missed cancers (0.3 %, 0.9 %, and 0.5 % in the first,
second, and third round, respectively, after 2 years of follow-up) [6 ]. Unfortunately, these proportions were not comparable to ours because of different
follow-up times.
The low incidence and characteristics of PCCRC found in our FIT-based screening cohort
reinforce the concept that quality of colonoscopy is of paramount importance [5 ]
[21 ]
[22 ]. In our cohort, all three patients presented with stage III CRC and had normal mismatch
repair protein expression and microsatellite stability, thus excluding a potential
accelerated carcinogenesis [23 ]. It is highly suggestive that they may correspond to missed lesions at the index
colonoscopy. The first lesion was a 15 mm sessile polyp located in the ascending colon.
Proximal location is a recognized risk factor for interval cancer because flat and
serrated lesions are more likely to arise in this area and which are easier to miss
[24 ]
[25 ]. The second one was a stenosing tumor in the sigmoid colon in a patient with diverticula.
Previous reports have shown that the presence of diverticula and a spastic sigmoid
colon might lead to an inadequate exploration of the fold of the colon and large polyps
might be undiagnosed [24 ]. The third lesion arose in a laterally spreading tumor in the rectum, a location
where blind spots are present without retroflexion. In such a context, the endoscopist’s
adenoma detection rate is the main quality indicator directly associated with the
risk for interval cancers [22 ]. Unfortunately, we did not have individual (per-endoscopist) adenoma detection rates
at that time, and withdrawal time and rectal retroflection were not reported and video-recordings
of the colonoscopies were not available. Continuous efforts to improve quality in
colonoscopy technique are required in order to strengthen the preventive role of current
screening strategies.
Our results also highlight specific situations in individuals with a positive FIT
and a negative colonoscopy, which deserve some comments. Firstly, with regard to anatomical
location of the subsequent relevant lesion, one-third of them were located in the
upper gastrointestinal tract. The FIT a priori does not detect digested blood because
it uses antibodies directed against human intact globin epitopes. Thus, the positivity
due to upper gastrointestinal bleeding lesions is controversial but it cannot be definitively
ruled out. Physiologically, the hemoglobin is cleaved to form heme and globin by gastric
pepsin protease, pancreatic proteases or both in the upper gastrointestinal tract
[26 ]. Part of the hematin is absorbed and the remainder is degraded mainly by colonic
bacteria to form porphyrins. The globin is digested by pepsin, pancreatic and intestinal
proteases to yield peptides and amino acids [26 ]. However, alterations in the digestive processes may facilitate the identification
of globin by the FIT [26 ]. For example, the hemoglobin degradation may be retarded in cases of marked reduction
in gastric acid secretion (i. e. vagotomy, gastrectomy or drugs) because a gastric
pH below 4 is required to convert pepsinogen in the activated pepsin [27 ]
[28 ]. In a study of participants in a FIT-based CRC screening program [29 ], the use of proton pump inhibitors was identified as an independent factor for false
positive results (OR, 1.8; 95 %CI, 1.1 – 2.9). Likewise, other factors such an accelerated
stool transit time or the intrinsic pattern of bleeding of a certain gastrointestinal
lesion (e. g. irregular flow and amount of blood) could also lead to a flow of small
quantities of intact blood into the colon [26 ]. Thus, since FIT can detect quantities as low as 0.3 mL of blood in stool [30 ], positivity due to lesions above the colon might be reasonably accepted. In our
cohort, these mechanisms might explain a limited number of cases, mainly those with
active bleeding lesions detected within the first 6 months after the index colonoscopy.
However, according to our results and in consonance with previous studies [31 ]
[32 ]
[33 ], the likelihood of having a relevant asymptomatic lesion in the upper gastrointestinal
tract is too low to support systematically performing an upper endoscopy in these
individuals.
Secondly, in our study, advanced comorbidities and chronic use of NSAIDs were significantly
associated with a higher likelihood of having a subsequent relevant lesion. The use
of NSAIDs has previously been described as a risk factor for a false positive FIT
[34 ]. These factors may cause transient inflammatory lesions or increase the physiologic
gastrointestinal bleeding and cause the false positive result.
Finally, the vast majority (95 %) of individuals did not present subsequent gastrointestinal
events after a 3- to 5-year follow-up period. The reasons for positivity remain elusive
but several hypotheses can be proposed. Despite explicit instructions about stool
sample collection, it is difficult to ensure an adequate compliance in cases of macroscopic
bleeding. The elapsed time since a positive FIT result until colonoscopy was 1 to
2 months. Therefore, it is possible that bleeding inflammatory lesions might have
disappeared at the time of examination. Also it is worthwhile mentioning that there
is a physiologic gastrointestinal blood loss through the small bowel of 0.5 to 1.5 mL
per day [26 ] that might be detected by the FIT if physiologic mechanisms are altered.
We are aware of some limitations of the study. Firstly, inaccessibility to a centralized
nationwide health registry for data cross-referencing may lead to missing information.
However, the characteristics of index colonoscopy are derived from the screening program
database, in which data are prospectively collected. In addition, follow-up information
was exhaustively completed through medical records, regional health service databases,
and successful telephonic interviews in 91 % of all patients ([Fig. 1 ]). Secondly, data collection after the index colonoscopy was based on medical consultation
and endoscopic procedures, which were performed according to predominant symptoms
rather than systematically assessed using a pre-established research protocol. We
also acknowledge that a subgroup of patients might have not had “enough” follow-up,
considering that the mean sojourn time of preclinical cancer progressing to a detected
cancer ranged from 4.5 to 5.8 years [35 ]. Thirdly, non-endoscopic or more primary care lesions such as hemorrhoids and fissures
might be missed. Moreover, it may be questionable how carefully these minor lesions
are documented in the colonoscopy report. Fourthly, since a comparison with individuals
with negative FIT is lacking, in some cases, it is difficult and perhaps daring to
consider a subsequent relevant lesion as a cause of previous FIT positivity.
In conclusion, in an organized population FIT-based CRC screening program, the cumulative
incidence of CRC after a negative colonoscopy was very low (0.4 %), but not zero.
Accordingly, continuous efforts are required to improve quality standards of colonoscopy
in order to strengthen the preventive role of the current CRC screening strategies.
On the other hand, the vast majority (95 %) of these individuals did not present any
subsequent relevant lesion related to FIT positivity. Thus, our results do not support
systematically performing additional endoscopic procedures in those individuals. From
a practical point of view, although a positive FIT preselects individuals who benefit
from more invasive testing because of their high risk of presenting colorectal neoplastic
lesions, once a high quality colonoscopy has been performed, the likelihood of missing
relevant lesions is negligible.
