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Sensitivity and Specificity of Community Fecal Immunotesting Screening for Colorectal Carcinoma in a High-Risk Canadian Population.

Noninvasive screening tests for colorectal carcinoma include fecal occult blood tests and fecal immunochemical tests (FIT). (1) Screening programs based on these tests not only are important for detecting early disease (2-4) but may also be efficiently promoted by primary care physicians. (5) Recent research, however, has indicated that FIT is more sensitive than fecal occult blood tests as well as being more convenient for patients. (6-10) Fecal immunochemical testing also offers advantages to clinical laboratories, including the potential for automation, the ability to customize the cutoff level to define a positive test, and improved cost-effectiveness. (11-16) Finally, by eliminating patients who do not need a colonoscopy, a FIT screening program may be more cost-effective than colonoscopy-based screening. (17)

Despite the numerous reported advantages of FIT as a screening modality, there are few community-based program evaluations describing the test characteristics of FIT (eg, sensitivity, specificity, and positive predictive value [PPV]) and therefore no data on which to evaluate existing and planned screening programs in Canada.

The purpose of this study was to describe the test characteristics of a FIT pilot program performed in Calgary, Alberta, Canada. Specifically, we compared FIT results with subsequent biopsy results to produce receiver operating characteristic curves for FIT and biopsy-proven neoplasias (colorectal carcinoma and colonic adenoma).


Ethics Statement

This research was approved by the University of Calgary Conjoint Research Ethics Board (ID 13-0376) prior to the start of data collection.

Data Sources

Data for this retrospective study were obtained from a pilot of community FIT screening using the FOBT-CHEK Sampling Bottle (Polymedco Inc, Cortland Manor, New York) FIT testing platform performed in Calgary, Alberta, Canada, between April 2011 and May 2012. Fecal immunochemical testing collection kits were distributed directly to patients by participating primary care physicians. Samples were returned to Calgary Laboratory Services for testing on an automated analyzer, OC-Sensor Diana (Polymedco, Inc), with a cutoff of 75 ng/mL, and the results were read by trained laboratory personnel. Calgary Laboratory Services is the sole provider of laboratory services to Calgary and surrounding areas (catchment population of 1.4 million persons). In the vast majority of cases 2 paired FIT tests were collected on consecutive days. Where 2 kits were collected, the higher of the 2 FIT values was used for analysis. For each FIT result we searched our laboratory information system for colon biopsy reports signed out in the 1-year period following the FIT. All biopsy results were interpreted by a pathologist as part of routine histologic assessment. Pathologists were blinded to the numeric results of the FIT results. Only biopsy results obtained within 1 year of the FIT were included.

Biopsy results were classified as nonneoplastic, colonic adenoma, and colorectal carcinoma. Nonneoplastic biopsies included normal mucosa and inflammatory and hyperplastic polyps. Colonic adenomas included sessile serrated adenoma, villous adenoma, tubulovillous adenoma, and tubular adenomas. For individuals with more than one biopsy, only the most advanced lesion was considered. For example, if a patient had both a carcinoma and a tubular adenoma, the case was considered as a carcinoma.

Statistical Analysis

Receiver operating characteristic curves were constructed for FIT quantitative values and carcinoma and for FIT quantitative values and adenoma. In addition to the overall analysis, subgroup analysis was performed for women and men and for ages older or equal to and younger than the mean subject age of 62. Area under the curve (AUC) values were then calculated for each receiver operating characteristic curve to determine the overall predicative strength of the associations. An AUC value of 0.8 is considered a strong predictor and a range between 0.5 and 0.6 is generally considered to represent a weak association. (18) Positive predictive values were also calculated. Statistical analyses were performed using SPSS for Macintosh version 21 (IBM SPSS Inc, Armonk, New York).


The operational pilot of FIT at our institution ran between April 2011 and May 2012. A total of 457 patients underwent FIT and had subsequent colon biopsy within a 1-year period and were therefore included in the analysis. Characteristics of patients and histology results are summarized in Table 1 and a flow diagram of the patients' eligibility and results is shown in Figure 1.

Figure 2, A and B, illustrates the receiver operating characteristic curves for FIT results and colorectal carcinoma for FIT results and colonic adenoma. The predictive ability for colorectal carcinoma was very good, with an AUC of 0.79 (95% confidence interval 0.71-0.87). In contrast to colorectal carcinoma, the predictive ability for colonic adenoma was poor, with an AUC of 0.60 (95% confidence interval 0.54-0.65). Table 2 indicates the sensitivities and specificities for FIT using the commonly accepted cutoff level of 75 ng/mL at our institution. Cross-tabulations were calculated from positive and negative FIT tests and biopsies and are shown in Table 3.

Although the majority of patients who underwent colonoscopy did so for routine screening or because of FIT-positive screening results, there were patients who were FIT negative who also had colonoscopy. Table 4 shows the indications for colonoscopy for patients with a negative FIT result. The histologic diagnoses for all 457 patients who underwent a colonoscopy are found in Table 5. Many patients had more than one polyp found during colonoscopy and had multiple diagnoses. Figure 3 shows the diagnoses of FIT-positive patients and the range of associated quantitative FIT results.

The PPV was 53% for all neoplasia. This value is within the range of prior studies, as shown in Table 6. For example, the PPV in our study is lower than that of Zubero et al, (19) who tested 2 different brands of FIT and found PPVs of 62.4% and 58.9%, but higher than that in another Canadian study (20) that demonstrated a 40% PPV (Table 6).


In this paper, we report the test characteristics from a FIT community screening program in Calgary, Alberta, Canada. Data from similar community programs are limited. The receiver operating characteristic curve for FIT test results and colorectal carcinoma showed good predictive ability with an AUC of 0.79 (95% confidence interval 0.71-0.87). However, the predictive ability for colonic adenomas was not as strong, with an AUC of 0.60 (95% confidence interval 0.54-0.65). The predictive ability was also better for men and for older individuals.

Several studies in Europe and Israel have shown higher sensitivities for FIT as compared with fecal occult blood tests. (6,8) Reported sensitivities in these studies have ranged from 40.5% to 94%. (7,8,21) Our results are likely more reflective of the expectations for a community-based program. We report AUCs for colorectal carcinoma in subgroup analysis of 0.75 to 0.85, which are considerably lower than those reported by Tao et al, (22) who reported AUCs for the 3 quantitative tests of 0.90 to 0.92. However, it is important to add that the high AUCs reported from Tao et al (22) were not from a community-based population. Another study by Haug et al (23) reported AUCs of 0.60 to 0.71 but is not directly comparable with our results because of their inclusion of certain types of adenoma along with colorectal carcinoma.

One potential weakness of our study was the time difference between when patients received FIT testing and when the biopsy was taken. Indeed, in some cases, there was up to a year between when the FIT was reported and when the colonoscopy was performed, which could allow for the possible interval progression of any lesions that were present at the time of FIT testing. However, this does represent a real-world situation, where, for reasons such as health system wait times or patient-related factors, colonoscopy may not be available immediately after a FIT is reported. A second weakness of the study is that as we used secondary data we were unable to control for the presence or absence of symptoms that may have prompted FIT testing or a colonoscopy in the first place. Lastly, as we studied patients who had undergone both FIT and colonoscopy, our sample was enriched for symptomatic and/or high-risk subjects. It should be noted, however, that this is a general limitation of observation studies using an invasive or potentially harmful gold standard.

In conclusion, our results show average performance for FIT as compared with previous studies and also indicate that although FIT is sensitive for colorectal carcinoma, the association is weaker for colonic adenomas. The relatively poor predictive ability for these colorectal carcinoma precursors suggests that reliance on screening by FIT testing alone may miss early lesions.

Please Note: Illustration(s) are not available due to copyright restrictions.


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Amber L. Crouse, BA; Lawrence De Koning, PhD; S. M. Hossein Sadrzadeh, PhD; Christopher Naugler, MD

Accepted for publication January 27, 2015.

From Calgary Laboratory Services, Calgary, Alberta, Canada (Ms Crouse and Drs Koning, Sadrzadeh, and Naugler); and the Departments of Pathology and Laboratory Medicine (Ms Crouse and Drs Koning, Sadrzadeh, and Naugler) and Family Medicine (Dr Naugler), University of Calgary, Calgary, Alberta, Canada.

The authors have no relevant financial interest in the products or companies described in this article.

Presented as a poster at the Canadian Association of Pathologists Conference; July 12-15, 2014; Toronto, Ontario, Canada.

Reprints: Christopher Naugler, MD, Department of Pathology and Laboratory Medicine, University of Calgary, 9-3535 Research Rd NW, Calgary, AB T2L 2K8, Canada (e-mail: christopher.naugler@cls.

Caption: Figure 1. Study flow diagram. Abbreviation: FIT, fecal immunotesting.

Caption: Figure 2. Receiver operating characteristic curves for a community trial of fecal immunochemical testing in Calgary, Alberta, Canada. Area under the curve was (A) 0.79 (95% confidence interval 0.71-0.87) for colorectal carcinoma and (B) 0.60 (95% confidence interval 0.54-0.65) for colonic adenoma.

Caption: Figure 3. Box and whisker plot showing the quantitative results from fecal immunochemical testing (FIT) screening by pathology diagnoses.
Table 1. Characteristics of Study Subjects

Characteristic                    Value

  No.                                 201
  Mean age (range), y          49 (34-83)
  No.                                 256
  Mean age (range), y          51 (33-84)
FIT result range                    0-981
Individuals with carcinoma             35
  as most serious lesion
Individuals with adenoma              209
  as most serious lesion (a)

Abbreviation: FIT, fecal immunochemical test.

(a) Includes sessile serrated adenoma, villous adenoma,
tubulovillous adenoma, and tubular adenoma.

Table 2. Test Characteristics of a Community-Based Pilot of Fecal
Immunotesting in Calgary, Alberta, Canada (a)

Lesion                 Sensitivity, %   Specificity, %

Tubular adenoma             36.4             62.2
Advanced adenoma (b)        49.5             62.7
Carcinoma                   82.9             60.0
  Tubular adenoma           38.1             56.8
  Advanced adenoma          51.6             58.6
  Carcinoma                 83.3             66.0
  Tubular adenoma           34.5             69.9
  Advanced adenoma          44.8             68.1
  Carcinoma                 82.6             65.9
Age [greater than or
  equal to] 62 y
  Tubular adenoma           40.0             55.0
  Advanced adenoma          46.5             56.9
  Carcinoma                 75.0             56.2
Age <62 y
  Tubular adenoma           32.7             70.7
  Advanced adenoma          50.0             69.4
  Carcinoma                100               64.8

Lesion                   AUC (95% CI)       P

Tubular adenoma        0.49 (0.41-0.54)    .47
Advanced adenoma (b)   0.57 (0.50-.064)    .05
Carcinoma              0.79 (0.71-0.87)   <.001
  Tubular adenoma      0.45 (0.36-0.54)    .24
  Advanced adenoma     0.53 (0.44-0.62)    .52
  Carcinoma            0.78 (0.66-0.91)    .01
  Tubular adenoma      0.52 (0.42-0.62)    .68
  Advanced adenoma     0.63 (0.52-0.74)    .03
  Carcinoma            0.81 (0.70-0.91)   <.001
Age [greater than or
  equal to] 62 y
  Tubular adenoma      0.44 (0.35-0.53)    .20
  Advanced adenoma     0.51 (0.41-0.62)    .77
  Carcinoma            0.75 (0.64-0.86)   <.001
Age <62 y
  Tubular adenoma      0.51 (0.42-0.61)    .79
  Advanced adenoma     0.60 (0.51-0.70)    .03
  Carcinoma            0.85 (0.78-0.93)   <.001

Abbreviations: AUC, area under the curve; CI, confidence interval.

(a) Sensitivity and specificity refer to the commonly used cutoff of
75 ng/mL.

(b) Includes sessile serrated adenoma, villous adenoma,
tubulovillous adenoma, and any high-grade dysplasia.

Table 3. Cross-Tabulation of Results (a


FIT        Positive   Negative

Positive     183         63
Negative     122         89

Abbreviation: FIT, fecal immunochemical test.

(a) A positive biopsy includes carcinoma and any adenoma subtype.
FIT positivity is defined as a quantitative value >75 ng/mL.

Table 4. Clinical History of All Patients Included for
Analysis With Both Fecal Immunochemical Test (FIT)
Screening and Colonoscopy

Clinical History                No. of Patients (a)

Routine screening                       159
FIT positive                            104
No history                               76
Gastrointestinal symptoms (b)            51
Family history                           30
History of prior polyps                  24
History of prior cancer                  14
Iron deficiency anemia                    7

(a) The total is greater than 457 as some individuals fit into more
than one category.

(b) Gastrointestinal symptoms include change in bowel habits,
abdominal pain, and rectal bleeding.

Table 5. Histologic Diagnosis From 983 Biopsies Taken From 457
Patients Undergoing Colonoscopy (a)

Diagnosis                       No. Positive

Carcinoma                            39
Sessile serrated adenoma             45
Tubulovillous adenoma                80
Villous adenoma                      10
Tubular adenoma                     436
Hyperplasic polyp                   180
Inflammatory polyp or colitis        63
No pathologic diagnosis             130

(a) The total is greater than 457 as some individuals had multiple

Table 6. Comparative Positive Predictive Value
(PPV) for All Neoplasia (Carcinoma and Adenomas)
in Related Studies

Source, y         Population         PPV for          Brand
                    Tested             All           of FIT

This study   Community                 53        FOBT-CHEK
               population and                      (Polymedco,
               patients receiving                  Inc, Cortland
               FIT and                             Manor, New
               colonoscopy                         York)
Zubero et    Patients scheduled        62.4      OC-Sensor
  al, (19)     for colonoscopy                     (Eiken
  2014         after a positive                    Chemical Co,
               FIT test result                     Taito-Ku,
                                                   Tokyo, Japan)
Zubero et    Patients scheduled        58.9      FOB Gold
  al, (19)     for colonoscopy                     (Sentinel
  2014         after a positive                    Diagnostics,
               FIT test result                     Milan,
Randell et   Symptomatic               40        Hemo Tech NS-
  al, (20)     patients and                        Plus (Alfresa
  2013         high-risk patients                  Pharma,
               scheduled for                       Chuo-Ku,
               colonoscopy                         Osaka, Japan)
Oono et      Recruited CRC             33.7      Auto iFOBT
  al, (24)     symptomatic                         (Alfresa
  2010         patients with a                     Pharma,
               range of                            Chuo-Ku,
               colorectal                          Osaka, Japan)
Levi et      Asymptomatic,             43.9      OC-MICRO
  al, (21)     symptomatic,                        (Eiken
  2007         and high-risk                       Chemical Co,
               patients referred                   Taito-Ku,
               from a clinic or                    Tokyo, Japan)
               treating physician
               or for elective

Abbreviations: CRC, colorectal carcinoma; FIT, fecal immunochemical
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Author:Crouse, Amber L.; De Koning, Lawrence; Sadrzadeh, S.M. Hossein; Naugler, Christopher
Publication:Archives of Pathology & Laboratory Medicine
Date:Nov 1, 2015
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