The colorectal cancer (CRC) screening project was undertaken by the Medical Advisory Secretariat (MAS) in collaboration with the Cancer Care Ontario (CCO).
In November 2007, the Ontario Health Technology Advisory Committee (OHTAC) MAS to conduct an evidence-based analysis of the available data with respect to colorectal cancer diagnosis and prevention. The general purpose of the project was to investigate the effectiveness, cost effectiveness, and safety of the various methods and techniques used for colorectal cancer screening in average risk people, 50 years of age and older.
The options currently offered for colorectal cancer screening were reviewed and five technologies were selected for review:
Computed tomographic (CT) colonography
Magnetic resonance (MR) colonography
Wireless capsule endoscopy (PillCam Colon)
Fecal occult blood test (FOBT)
In this review, colonoscopy was considered as the “gold standard” technique by which the effectiveness of all other modalities could be evaluated. An economic analysis was also conducted to determine cost-effectiveness of different screening modalities.
Evidence-based analyses have been prepared for each of these technologies, as well as summary document that includes an economic analysis, all of which are presented at the MAS Web site: http://www.health.gov.on.ca/english/providers/program/mas/tech/techmn.html
The objective of this evidence review is to examine the effectiveness and cost-effectiveness of fecal occult blood testing (FOBT), including guaiac FOBT (gFOBT) and immunochemical FOBT (iFOBT), for use in colorectal cancer (CRC) screening in asymptomatic, average-risk adults.
Is the use of gFOBT or iFOBT associated with a reduction in CRC and overall mortality?
What are the sensitivity and specificity of gFOBT and iFOBT for the detection of 1) CRC and 2) large polyps (≥ 1 cm)?
CRC is the most common cause of non-tobacco related cancer death in Canada. It has been estimated that in 2007, 7,800 people were diagnosed with CRC in Ontario and 3,250 died from the disease, making the province’s incidence and mortality rate of CRC amongst the highest in the world.
Description of Technology/Therapy
There are two general types of FOBT that are categorized according to the analyte detected: guaiac FOBT (gFOBT) and immunochemical FOBT (iFOBT). Blood in the stool is a nonspecific finding but may originate from CRC or larger (>1 cm) polyps (small adenomatous polyps do not tend to bleed). Bleeding from cancers and larger polyps may be intermittent and not always detectable in a single sample. The FOBT thus requires regular testing that consists of collecting specimens from consecutive bowel movements. A positive gFOBT or iFOBT involves a diagnostic workup with colonoscopy to examine the entire colon in order to rule out the presence of cancer or advanced neoplasia.
Methods of Evidence-Based Analysis
A literature search was conducted from January 2003 to June 2008 that included OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), The Cochrane Library, and the International Agency for Health Technology Assessment/Centre for Review and Dissemination.
Patients at average risk for CRC
All patients must be at least 50 years of age
Biennial FOBT as a screening modality and use of colonoscopy as the reference standard
Systematic reviews and randomized controlled trials (RCTs)
Outcomes: CRC mortality, overall mortality, sensitivity, specificity, adverse effects
Studies involving fewer than 100 patients
Studies that do not report sufficient data for analysis
Comparisons of Interest
Evidence exists for these comparisons of interest:
gFOBT compared with the reference “gold standard” colonoscopy (or double-contrast barium enema where colonoscopy is incomplete or contraindicated)
iFOBT compared with the reference gold standard colonoscopy (or DCBE where colonoscopy is incomplete or contraindicated)
gFOBT compared with iFOBT
The quality of the diagnostic studies was examined according to the ‘GRADE Working Group criteria’ for grading quality of evidence and strength of recommendations for diagnostic tests and strategies.
Summary of Findings
There is limited direct/indirect evidence that iFOBT has sensitivity/specificity superior to that of unrehydrated gFOBT for CRC detection:
sensitivity for gFOBT:
pooled iFOBT sensitivity:
There is evidence that iFOBT and gFOBT have lower sensitivities for adenoma detection than for CRC detection:
sensitivity for rehydrated gFOBT
pooled iFOBT sensitivity
No trials have examined CRC mortality outcomes after repeated testing of iFOBT.
Two RCTs from the United Kingdom and Denmark showed significant reduction in CRC mortality using unrehydrated gFOBT biennially
Relative risk reductions of 13% (UK trial) and 16% (Danish trial); absolute difference of 0.1% (UK trial) and 0.2% (Danish trial).
No significant reduction in overall mortality
Interval cancers (CRC that develop in the intervals between routine screening)
United Kingdom trial: 236 CRCs detected by positive test, 236 interval CRCs after negative test
Danish trial: 120 CRCs detected by positive test, 146 interval CRCs after negative test
Unrehydrated gFOBT has low sensitivity for CRC detection (45% in the UK trial and 54% in the Danish trial).
true positive rate
false positive rate
true negative rate
false negative rate
Guaiac FOBT – GRADE Quality of Evidence for Interventions
CRC indicates colorectal cancer; FOBT, fecal occult blood test; GRADE, Grading of Recommendations Assessment, Development and Evaluation; RCT, randomized controlled trial.
Unlikely to be an important uncertainty.
GRADE Quality of Evidence for Diagnostic Tests: Implications of Testing Focusing on Accuracy
Benefit from diagnosis and treatment after confirmatory colonoscopy
Small risk of bowel perforation during colonoscopy
Benefit of reassurance
Anxiety/worry leading up to confirmatory colonoscopy
Small risk of bowel perforation during confirmatory colonoscopy
Detriment from delayed diagnosis
Some uncertainty (until after confirmatory colonoscopy)
FOBT indicates fecal occult blood test; GRADE, Grading of Recommendations Assessment, Development and Evaluation.
Immunochemical FOBT – GRADE Quality of Evidence for Diagnostic Studies
FN indicates false negative; FOBT, fecal occult blood test; FP, false positive; Development and Evaluation; TN, true negative; TP, true positive.
Uncertainty until after confirmatory colonoscopy
Stress/worry for patient until confirmatory colonoscopy
Detrimental effects due to delayed diagnosis.
For these 3 reasons, downgrade quality from High to Moderate.
For these 3 reasons, downgrade quality from Moderate to Low.
Considerations for the Ontario Health System
Executive Summary Table 4 shows the potential system pressures and benefit/risk analysis for the use of FOBT and colonoscopy to screen for CRC in average-risk adults, ages 50 and over in Ontario.
Summary of Potential System Pressures for FOBT Screening
Prevent and detect
Every 10 years
Must repeat at regular intervals
Every 2 years
Must repeat at regular intervals
Used as gold standard in studies
Intervention GRADE quality: High (gFOBT)
Diagnostic GRADE quality: Low (iFOBT)
No RCTs examining the effectiveness of repeated iFOBT on CRC mortality reduction were identified
Limited direct/indirect evidence that iFOBT has superior sensitivity/specificity to unrehydrated gFOBT for detection of CRC
0.1% risk of serious bleeding and perforation requiring surgery
0.3% risk of serious complications (stroke/bleeding requiring hospitalization/ myocardial infarction)
High interval cancer rate
The small benefit in CRC mortality reduction (absolute difference 0.1% to 0.2%) also coincides with a 0.3% risk of serious complications.
No food 1 day prior to exam
Complete bowel preparation
Eliminate citrus fruit and juices and vitamin C from diet for 3 days prior to/during stool collection.
Person applies 2 samples per bowel movement (each occurring on 3 different days) onto test areas of FOBT cards.
Increased demand for colonoscopies and colonoscopists or nurses who perform colonoscopies.
Patient receives kit from family physician, pharmacist
Patients mail completed FOBT kit to participating laboratory
Results sent back to patient
Increased demand for colonoscopies for positive patients
Removal of polyp during colonoscopy or surgery
Referral to colonoscopy
2nd of 5 choices in a patient survey study
5th of 5 choices in a patient survey study
FOBT indicates fecal occult blood test;; gFOBT, guaiac FOBT; GRADE, Grading of Recommendations Assessment, Development and Evaluation; iFOBT, immunochemical FOBT; RCT, randomized controlled trial.