Canada has one of the highest rates of colorectal cancer (CRC) in the world, with an estimated 25,100 cases in 2015 [
In light of emerging evidence, the provincial CRC screening program is seeking guidance for CRC screening of average risk individuals in Ontario. Cancer Care Ontario’s Prevention and Cancer Control portfolio and the Program in Evidence-Based Care (PEBC) developed this evidentiary base to help inform the CRC screening program in Ontario, ColonCancerCheck.
The evidence supporting primary screening tests for CRC, ages of initiation and cessation for CRC screening, and screening intervals for selected CRC screening tests in people at average risk for CRC was systematically reviewed to develop this evidentiary base. Below, the methods and key findings of the systematic review are summarized. The full evidentiary base is available online [
The purpose of this systematic review is to evaluate the existing evidence concerning screening of adults at average risk for CRC in the context of an organized, population-based screening program. The main objectives are to identify the following: The benefits and harms of screening in this population. The optimal primary CRC screening test(s) for this population. The appropriate ages of initiation and cessation for screening in this population. The intervals at which people at average risk should be recalled for CRC screening.
The target population includes primary care providers, endoscopists, policy-makers, and program planners in Ontario.
Primary Research Question is as follows: How do different screening tests, individually or in combination, perform in average risk people in preventing CRC-related mortality or all-cause mortality or in decreasing the incidence of CRC? Secondary outcomes include the detection of cancer or its precursors, screening participation rate, adverse effects of tests, and test characteristics, such as sensitivity, specificity, positive predictive value, negative predictive value, and proportion of false-positives or of false-negatives.
Secondary Research Questions are as follows: What are the appropriate ages of initiation and cessation for screening in people at average risk for CRC? Is there a relationship between age and the effectiveness of CRC screening? What are the appropriate intervals between CRC screening tests (by test)? Is there a relationship between screening intervals and the effectiveness and risks of screening?
The authors of this evidentiary base (working group) consisted of one primary care physician, one colorectal surgeon, one expert in public health screening, one policy analyst from the Ontario CRC screening program, two methodologists, and three gastroenterologists. The PEBC, a provincial program of Cancer Care Ontario, is supported by the Ontario Ministry of Health and Long-Term Care. All work produced by the PEBC and any associated programs is editorially independent from the ministry.
A two-stage method was used. It is summarized here and described in more detail as follows: Search and evaluation of existing systematic reviews: if existing systematic reviews were identified that addressed the research questions and were of reasonable quality, then they were included as a part of the evidentiary base. Original systematic review of the primary literature: this review focused on areas not covered by existing and accepted reviews.
A systematic search was conducted in OVID MEDLINE (2006 to September 3, 2014), EMBASE (2006 to September 3, 2014), the Cochrane Library (Issue: 2–4, October 2013), and the American Society of Clinical Oncology (ASCO) conference proceedings (2009 to 2013). Details of the literature search strategy can be found online [
Systematic reviews were included if they addressed at least one of the research questions, they evaluated randomized or nonrandomized control trials of asymptomatic average risk subjects undergoing CRC screening, the literature search strategy for the existing systematic review was reproducible (i.e., reported) and appropriate, the existing systematic review reported the sources searched, as well as the dates that were searched.
Identified systematic reviews were assessed using the Assessing of Methodological Quality of Systematic Reviews (AMSTAR) tool [
If no existing systematic review was identified for a given test or question, or if identified reviews were incomplete, a systematic review of the primary literature was performed. Articles in reference lists from included studies were also searched. The scope of the primary literature review was tailored to address the gaps in the incorporated existing systematic reviews (e.g., subject areas covered and time frames covered). The criteria for the primary literature are described as follows.
Randomized controlled trials (RCTs) (primary research question and secondary research questions 1 and 2) that could be identified directly from the search or from reference sections of systematic reviews. Cohort/case-control studies, minimum study size Evidence from nonrandomized prospective comparative studies with historical or contemporaneous controls, with the consensus of the working group, when there were gaps in available evidence from RCTs. Studies preferred with asymptomatic average risk subjects and population-based studies that did not oversample adults with symptoms of CRC or a family history of CRC which were also considered acceptable. For conference abstracts: RCTs (all questions). The following screening tests considered for inclusion:
fecal-based tests including gFOBT, fecal immunochemical test (FIT), stool DNA panel (stool DNA), and fecal M2-PK, blood tests (Cologic®, ColonSentry®, mSEPT9, metabolomics, and hydroxylated polyunsaturated long chain fatty acids), endoscopic tests including flexible sigmoidoscopy (FS), colonoscopy, and capsule colonoscopy, radiological tests including double-contrast barium enema (DCBE) and computed tomography colonography (CT colonography).
Letters, comments, or editorials. Studies that included a population enriched with subjects with symptoms of CRC or a family history of CRC. Nonsystematic reviews. Non-English-language publications.
One of the two reviewers (NI and EV) independently reviewed the titles and abstracts resulting from the search. For items that warranted full-text review, NI or EV reviewed each item independently. However, in uncertain cases, a second reviewer (JT) was asked to review them.
Data from the included studies were independently extracted by NI and EV. If there was more than one publication for the same study, only the most updated or recent versions of the data were reported in the result. All extracted data and information were audited by an independent auditor.
Important quality features, such as randomization details, sample size and power, intention-to-screen (ITS) analysis, length of follow-up, and funding, for each RCT, were extracted. The quality of observational studies was assessed using a modified Newcastle-Ottawa Scale [
When clinically homogenous results from two or more trials were available, a meta-analysis was conducted using review manager software (RevMan 5.3) provided by the Cochrane Collaboration [
In order to have comparable control rates across all gFOBT and FS trials, the control rates for the no screening groups in the gFOBT and FS trials were combined and calculated from the total number of cases across all gFOBT and FS trials over the total number of person-years across all gFOBT and FS trials.
Statistical heterogeneity was calculated using
The working group members met in person on four occasions to develop evidence-based conclusions through consensus. For each comparison (e.g., gFOBT versus no screening) the working group assessed the quality of the body of evidence for each outcome using the GRADE process [
Description of the quality of evidence grades according to Grading of Recommendations, Assessment, Development and Evaluations (GRADE) [
Grade | Definition |
---|---|
High | We are very confident that the true effect lies close to that of the estimate of the effect |
Moderate | We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different |
Low | Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect |
Very low | We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect |
A total of 7538 studies were identified and 378 were selected for full-text review. Of those, 48 met the predefined eligibility criteria for this systematic review. An additional 27 articles were found from the reference lists. After our literature search, we became aware of and included an updated publication for one of the FS screening RCTs that had already been identified [
Summary of included studies by research question.
Research question and references |
Systematic reviews | Outcomes | RCTs | Prospective studies | Retrospective studies | Case-control studies |
---|---|---|---|---|---|---|
| ||||||
gFOBT versus no screening |
1 | CRC mortality | 4 | |||
Complications from tests | 3 | |||||
All-cause mortality | 4 | |||||
CRC incidence | 5 | |||||
|
||||||
FS versus no screening |
1 | CRC mortality | 4 | |||
Complications from tests | 5 | |||||
All-cause mortality | 4 | |||||
CRC incidence | 4 | |||||
|
||||||
Colonoscopy versus no screening |
2 | CRC mortality | 2 | 1 | ||
Complications from tests | 11 | 4 | ||||
CRC incidence | 2 | 3 | ||||
|
||||||
mSEPT9 alone |
Diagnostic test accuracy outcomes | 1 | ||||
|
||||||
Fecal M2-PK alone |
Diagnostic test accuracy outcomes | 1 | 1 | |||
|
||||||
Stool DNA versus gFOBT or FIT |
Diagnostic test accuracy outcomes | 3 | 1 | |||
|
||||||
FIT versus gFOBT |
1 | Complications from tests | 1 | |||
CRC/advanced adenoma detection rate (ITS) | 5 | |||||
CRC/advanced adenoma detection rate (PP) | 5 | |||||
Participation rate | 6 | |||||
Diagnostic test accuracy outcomes, false-positives/total screened | 5 | |||||
|
||||||
CT colonography versus colonoscopy |
Complications from tests | 1 | ||||
CRC/advanced adenoma detection rate (ITS) | 1 | |||||
CRC/advanced adenoma detection rate (PP) | 1 | |||||
Participation rate | 1 | |||||
|
||||||
Capsule colonoscopy versus colonoscopy |
Complications from tests | 1 | ||||
Adenoma detection rate (PP) | 1 | |||||
|
||||||
Fecal-based tests versus endoscopy |
||||||
FIT versus colonoscopy | 3 | Complications from tests | 2 | |||
CRC/advanced adenoma detection rate (ITS) | 3 | |||||
Participation rate | 3 | |||||
FIT versus FS | Complications from tests | 1 | ||||
CRC/advanced adenoma detection rate (ITS) | 3 | |||||
Participation rate | 3 | |||||
gFOBT versus colonoscopy | Complications from tests | 1 | ||||
Participation rate | 2 | |||||
gFOBT versus FS | Complications from tests | 1 | ||||
CRC/advanced adenoma detection rate (ITS) | 2 | |||||
Participation rate | 4 | |||||
gFOBT versus gFOBT + FS | Complications from tests | 1 | ||||
CRC/advanced adenoma detection rate (ITS) | 2 | |||||
Participation rate | 3 | |||||
|
||||||
|
||||||
gFOBT versus no screening |
CRC mortality by age group | 2 | ||||
|
||||||
FS versus no screening |
CRC mortality by age group | 2 | ||||
CRC incidence by age group | 4 | |||||
|
||||||
Colonoscopy versus no screening |
CRC risk by age group | 1 | ||||
|
||||||
|
||||||
gFOBT |
CRC mortality by interval (annual versus biennial) | 1 | ||||
All-cause mortality by interval (annual versus biennial) | 1 | |||||
CRC incidence by interval (annual versus biennial) | 1 | |||||
|
||||||
FIT |
CRC/advanced adenoma detection rate by interval (1 versus 2 versus 3 years) | 1 | ||||
Participation rate by interval (1 versus 2 versus 3 years) | 1 |
CRC: colorectal cancer; CT: computed tomographic; DNA: deoxyribonucleic acid; FIT: fecal immunochemical test; FS: flexible sigmoidoscopy; gFOBT: guaiac fecal occult blood test; ITS: intention to screen; PP: per protocol; RCT: randomized controlled trial.
The following are the conclusions developed by the working group based on the review of the evidence and meta-analyses. When discussing the effects of various screening tests, the reported outcomes vary by test. There was strong agreement among the members of the working group that CRC-related mortality and complications from screening tests were critical outcomes for recommendation development. All-cause mortality, CRC incidence, participation rate, and diagnostic outcomes were considered important outcomes of interest.
There was strong evidence to support the use of fecal tests for occult blood to screen people at average risk for CRC.
The overall certainty of the evidence was high, suggesting a definite reduction in CRC-related mortality (Table
GRADE evidence profile—gFOBT versus no screening.
Quality assessment | Number of patients | Effect | Quality1 | Importance | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Number of studies | Design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | gFOBT (cases/person-years) | No screening (cases/person-years) | Relative |
Absolute | ||
CRC mortality (followup: range 17–30 years) | ||||||||||||
4 | Randomised trials | Not serious | Not serious | Not serious | Not serious | Not serious | 2027/2674854 (0.08%) | 2326/2669246 (0.09%) |
|
113 fewer per 1000000 (from 70 fewer to 157 fewer) |
|
Critical |
Control (gFOBT + FS) = 0.06% |
78 fewer per 1000000 (from 48 fewer to 108 fewer) | |||||||||||
|
||||||||||||
Complications from tests (from Holme et al. 2013 [ |
||||||||||||
3 | Randomized trials | Not serious | Not serious | Not serious | Not serious | Not serious | N/A3 |
|
Critical | |||
|
||||||||||||
All-cause mortality (follow-up: range 17–30 years) | ||||||||||||
4 | Randomized trials | Not serious | Not serious | Not serious | Not serious | Not serious | 74,481/2,674,854 (2.8%) | 74,174/2,669,246 (2.8%) |
|
0 fewer per 1,000,000 (from 278 fewer to 278 more) |
|
Important |
Control (gFOBT + FS) = 1.85% |
0 fewer per 1000000 (from 185 fewer to 185 more) | |||||||||||
|
||||||||||||
CRC incidence (follow-up: range 17–30 years) | ||||||||||||
5 | Randomized trials | Not serious | Not serious | Serious4 | Not serious | Not serious | 4324/2,434,487 (0.2%) | 4489/2,431,961 (0.2%) |
|
74 fewer per 1,000,000 (from 37 more to 185 fewer) |
|
Important |
Control (gFOBT + FS) = 0.16% |
64 fewer per 1,000,000 (from 32 more to 160 fewer) |
CI: confidence interval; CRC: colorectal cancer; FS: flexible sigmoidoscopy; gFOBT: guaiac fecal occult blood test; GRADE: Grading of Recommendations, Assessment, Development and Evaluations; ITS: intention to screen; N/A: not applicable; RR: relative risk.
1GRADE working group grades of evidence:
(i) High quality: we are very confident that the true effect lies close to that of the estimate of effect.
(ii) Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
(iii) Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
(iv) Very low quality: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
2Major complication defined as bleeding, perforation, or death within 30 days of screening, follow-up colonoscopy, or surgery.
3Holme et al. 2013 [
4Goteborg trial used sigmoidoscopy and double-contrast barium enema as reference standard; other trials used colonoscopy.
The overall certainty of the evidence was moderate (Table While there were well-designed randomized controlled trials (RCTs) comparing FIT with gFOBT, the outcomes of these trials (participation and detection rates) were considered to be less important than CRC-related mortality. However, it was anticipated that the reduction in CRC-related mortality and the complications resulting from screening with FIT would be at least equivalent to those observed from screening with gFOBT. FIT’s greater sensitivity for detection of CRC and advanced adenomas compared with gFOBT suggests that the reduction in CRC incidence with FIT could be greater than with gFOBT; however, the magnitude and significance of any additional benefit of FIT over gFOBT are unknown. It is important to highlight that the FIT positivity threshold selected would be an important determinant of the magnitude of the benefits and harms of FIT relative to gFOBT.
GRADE evidence profile—gFOBT versus FIT.
Quality assessment | Number of patients | Effect | Quality | Importance | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Number of studies | Design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | FIT | gFOBT | Relative (95% CI) | Absolute | ||
Complications from tests | ||||||||||||
1 | Randomized trial | Not serious | Not serious | Not serious | Serious1 | Not serious | Not pooled |
|
Critical | |||
|
||||||||||||
CRC/advanced adenoma detection rate (ITS) | ||||||||||||
5 | Randomized trials | Not serious | Not serious | Serious2 | Not serious | Not serious | 278/24,288 (1.1%) | 129/27,346 (0.5%) |
|
5 more per 1000 (from 3 more to 9 more) |
|
Important |
|
||||||||||||
CRC/advanced adenoma detection rate (PP) | ||||||||||||
5 | Randomized trials | Not serious | Not serious | Serious2 | Not serious | Not serious | 278/12,146 (2.3%) | 129/10,976 (1.2%) |
|
10 more per 1000 (from 4 more to 18 more) |
|
Important |
|
||||||||||||
False-positive screening test results | ||||||||||||
5 | Randomized trials | Not serious | Serious3 | Not serious | Not serious | Not serious | 385/24,288 (1.6%) | 188/27,346 (0.7%) |
|
8 more per 1000 (from 0 fewer to 23 more) |
|
Important |
|
||||||||||||
Participation rate | ||||||||||||
6 | Randomized trials | Not serious | Serious4 | Not serious | Not serious | Not serious | 12,271/24,490 (50.1%) | 11075/27,548 (40.2%) |
|
64 more per 1000 (from 20 more to 113 more) |
|
Important |
CI: confidence interval; CRC: colorectal cancer; FIT: fecal immunochemical test; gFOBT: guaiac fecal occult blood test; GRADE: Grading of Recommendations, Assessment, Development and Evaluations; ITS: intention to screen; PP: per protocol; RR: relative risk.
1Only one study.
2Surrogate outcome for CRC mortality.
3Heterogeneity: Tau2 = 0.61; Chi2 = 56.96, df = 3 (
4Heterogeneity: Tau2 = 0.01; Chi2 = 107.18, df = 5 (
There was strong evidence to support the use of flexible sigmoidoscopy (FS) to screen people at average risk for CRC. There was no direct evidence to support the use of colonoscopy to screen people at average risk for CRC, but evidence from FS informed the assessment of the benefits and harms of colonoscopy in screening people at average risk for CRC.
The overall certainty of the evidence was high, suggesting that FS has a definite effect on CRC-related mortality and incidence when compared with no screening (Table
GRADE evidence profile—FS versus no screening.
Quality assessment | Number of patients | Effect | Quality | Importance | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Number of studies | Design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | FS (cases/person-years) | No screening (cases/person-years) | Relative |
Absolute | ||
CRC mortality (follow-up: 6–12 years) | ||||||||||||
4 | Randomized trials | Not serious | Not serious | Not serious | Not serious | Not serious | 576/1,902,184 (0.03%) | 1321/3,114,546 (0.04%) |
|
119 fewer per 1,000,000 (from 85 fewer to 148 fewer) |
|
Critical |
Control (gFOBT + FS) = 0.06% |
168 fewer per 1,000,000 (from 120 fewer to 210 fewer) | |||||||||||
|
||||||||||||
Complications from tests (from Holme et al. 2013 [ |
||||||||||||
5 | Randomized trials | Not serious | Not serious | Not serious | Not serious | Not serious | N/A2 |
|
Critical | |||
|
||||||||||||
All-cause mortality (follow-up: 6–12 years) | ||||||||||||
4 | Randomized trials | Not serious | Not serious | Not serious | Not serious | Not serious | 19,525/1,902,184 (1.0%) | 32,903/3,114,546 (1.1%) |
|
317 fewer per 1,000,000 (from 106 fewer to 423 fewer) |
|
Important |
Control (gFOBT + FS) = 1.85% |
555 fewer per 1,000,000 (from 185 fewer to 740 fewer) | |||||||||||
|
||||||||||||
CRC incidence (follow-up: 6–12 years) | ||||||||||||
4 | Randomized trials | Not serious | Not serious | Not serious | Not serious | Not serious | 2218/1,860,990 (0.1%) | 4579/3,067,081 (0.1%) |
|
328 fewer per 1,000,000 (from 254 fewer to 388 fewer) |
|
Important |
Control (gFOBT + FS) = 0.16% |
352 fewer per 1,000,000 (from 272 fewer to 416 fewer) |
CI: confidence interval; CRC: colorectal cancer; FS: flexible sigmoidoscopy; gFOBT: guaiac fecal occult blood test; GRADE: Grading of Recommendations, Assessment, Development and Evaluations; RR: relative risk; N/A: not applicable.
1Major complication rate included bleeding, perforation, or death within 30 days of screening, follow-up colonoscopy, or surgery.
2Holme et al. 2013 [
The overall certainty of direct evidence supporting the use of colonoscopy to screen people at average risk for CRC was very low when compared with no screening (Table It is anticipated that the benefit of screening with colonoscopy would be at least equivalent to that observed for screening with FS; however, the magnitude of additional benefit over FS, if any, is unknown. The magnitude of additional undesirable effects of colonoscopy relative to FS is also unknown.
GRADE evidence profile—colonoscopy and CRC-related mortality and incidence.
Quality assessment | Effect | Quality | Importance | ||||||
---|---|---|---|---|---|---|---|---|---|
Number of studies | Design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | Relative (95% CI) | ||
CRC mortality (from Brenner et al. 2014) [ | |||||||||
3 | Observational studies | Serious1 | Not serious | Not serious | Not serious | Not serious | RR 0.32 (0.23–0.43) |
|
Critical |
|
|||||||||
Complications from tests (perforations, bleeding, and deaths) | |||||||||
15 | Observational studies | Not serious | Not serious | Not serious | Not serious | Not serious | N/A2 |
|
Critical |
|
|||||||||
CRC incidence (from Brenner et al. 2014) [ | |||||||||
5 | Observational studies | Serious1 | Serious3 | Not serious | Not serious | Not serious | RR 0.31 (0.12 to 0.77) |
|
Important |
CI: confidence interval; CRC: colorectal cancer; GRADE: Grading of Recommendations, Assessment, Development and Evaluations; N/A: not applicable.
1Mixed study designs included case-control and retrospective.
2The risks of perforation or bleeding were less than 1% ranging from 0% to 0.22% for perforations and 0% to 0.19% for bleeding.
3Heterogeneity: Tau2 = 1.0; (
There was insufficient evidence to determine how fecal tests for occult blood perform compared with lower bowel endoscopy to screen people at average risk for CRC (Supplementary Tables 1 to 5 and Supplementary Figures 11 to 19). The studies that compared one-time fecal tests for occult blood to lower bowel endoscopy were heterogeneous, with few comparisons where data could be pooled. However, in general, the evidence suggested that participation was higher and detection rate was lower with fecal-based tests compared with endoscopic tests. The overall certainty of the evidence was low. CRC-related mortality was not evaluated and the design of the studies favoured endoscopic tests because the comparison was to one-time fecal-based testing (rather than repeated testing over time, which is how these tests are used in usual practice). There was significant heterogeneity in participation. The undesirable anticipated effects of endoscopy (including follow-up endoscopy for people with positive fecal tests) are probably small. It is uncertain whether the desirable effects are large relative to the undesirable effects.
There was insufficient evidence to determine how computed tomography colonography performs compared with colonoscopy to screen people at average risk for CRC (results not shown; see [ The overall certainty of the evidence was low. The desirable and undesirable anticipated effects were uncertain.
There was insufficient evidence to determine how capsule colonoscopy performs compared with colonoscopy to screen people at average risk for CRC (results not shown; see [ The overall certainty of the evidence was very low. The desirable and undesirable anticipated effects were uncertain.
There was no evidence to support the use of DCBE to screen people at average risk for CRC. Since 2006, there has been no new published evidence on this topic. Most recent CRC guidelines except for a 2008 guideline by the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology [
There was insufficient evidence to determine how stool DNA performs compared with gFOBT or FIT to screen people at average risk for CRC (results not shown; see [ The overall certainty of the evidence was very low. The desirable and undesirable anticipated effects were uncertain.
There was insufficient evidence to support the use of mSEPT9 to screen people at average risk for CRC (results not shown; see [ The overall certainty of the evidence was very low. The desirable and undesirable anticipated effects were uncertain.
There was insufficient evidence to support the use of fecal M2-PK to screen people at average risk for CRC (results not shown; see [ The overall certainty of the evidence was very low. The desirable and undesirable anticipated effects were uncertain.
There was no evidence to support the use of other metabolomic tests (e.g., low levels of hydroxylated polyunsaturated long chain fatty acids [Cologic]) to screen people at average risk for CRC.
Currently, the Ontario CRC screening program recommends that average risk individuals initiate screening with gFOBT beginning at 50 years of age and ending at age 74. There was insufficient evidence to support changing the ages of initiation and cessation for CRC screening with gFOBT in Ontario (results not shown; see [ The overall certainty of the evidence was very low. There was insufficient evidence to demonstrate differences in reduction of CRC mortality using gFOBT across age groups. The desirable and undesirable anticipated effects across age groups were uncertain.
There was insufficient evidence to recommend ages of initiation or cessation when screening with FS in people at average risk for CRC (results not shown; see [ The overall certainty of the evidence was very low. There was insufficient evidence to demonstrate differences in reduction of CRC mortality or incidence using FS across age groups. The desirable and undesirable anticipated effects across age groups were uncertain. Of the four large FS RCTs, three examined “once in a lifetime” FS between the ages of 55 and 64, while the fourth RCT examined baseline FS between the ages of 55 and 74 with a second FS after three or five years.
There was insufficient evidence to recommend an age of initiation or cessation to screen with colonoscopy in people at average risk for CRC (results not shown; see [ The overall certainty of the evidence was very low. There was insufficient evidence to demonstrate differences in CRC detection using colonoscopy across age groups. The desirable and undesirable anticipated effects across age groups were uncertain. Currently, the Ontario CRC screening program does not recommend colonoscopy to screen persons at average risk for CRC. The program does recommend colonoscopy in people at increased risk (one or more first-degree relatives with CRC) starting at 50 years of age or 10 years younger than the age at which the relative was diagnosed, whichever occurred first.
There were no studies that met our inclusion criteria for age of initiation/cessation for FIT.
There was evidence to suggest that either annual or biennial screening using gFOBT in people at average risk for CRC reduces CRC-related mortality (results not shown; see [ The overall certainty of the evidence was moderate. The desirable anticipated effects on CRC mortality were small and similar for annual or biennial screening. The undesirable anticipated effects were not reported for each interval group. Anticipated harms associated with gFOBT (including follow-up colonoscopy for people with positive tests) were small for biennial screening and were likely to be greater for annual screening. In addition, annual screening is anticipated to increase burden to the participant.
There was insufficient evidence to recommend an interval to screen people at average risk for CRC using FIT (results not shown; see [ The overall certainty of the evidence was very low. The desirable and undesirable anticipated effects were uncertain.
There were no studies that met our inclusion criteria for screening intervals for FS or colonoscopy.
This evidentiary base summarizes the known clinical effectiveness and safety of CRC screening tests. Concurrently, the Canadian Task Force on Preventive Health Care (CTFPH) [
The evidence from the current review is central to the ongoing development of Ontario’s CRC screening program. However, this evidentiary base is necessary but not sufficient to guide program development as other context-specific criteria such as cost-effectiveness, existing program design, and public acceptability and feasibility (from an organizational and economic perspective) must be considered. In addition, the program must also consider the balance between choice and informed decision making and issues not well addressed by the evidence such as how to best implement CRC screening when there is more than one CRC screening test supported by high-quality evidence. An expert panel comprising members from national and international screening programs, primary care physicians, general surgeons, gastroenterologists, pathologists and laboratory medicine professionals, nurse endoscopists, and members of the public was convened to provide guidance on how to incorporate this evidence in light of the other issues listed above. Their level of agreement with the conclusions is reflected in Table
Responses of the expert panel to the working group’s conclusions.
Reviewer ratings ( | |||||
---|---|---|---|---|---|
Conclusions | Strongly disagree (%) | Disagree (%) | Neither agree nor disagree (%) | Agree (%) | Strongly agree |
( |
0 | 0 | 1 (4) | 10 (37) | 16 (59) |
( |
0 | 0 | 0 | 7 (26) | 20 (74) |
( |
0 | 2 (8) | 2 (8) | 14 (54) | 8 (31) |
( |
0 | 2 (8) | 4 (15) | 13 (50) | 7 (27) |
( |
0 | 0 | 1 (4) | 8 (33) | 15 (63) |
( |
0 | 0 | 0 | 1 (4) | 23 (96) |
( |
0 | 0 | 2 (8) | 0 | 23 (92) |
( |
0 | 0 | 0 | 8 (33) | 16 (67) |
( |
0 | 0 | 0 | 2 (8) | 23 (92) |
( |
0 | 0 | 0 | 3 (12) | 23 (89) |
( |
0 | 0 | 1 (4) | 2 (9) | 20 (87) |
( |
0 | 1 (4) | 1 (4) | 9 (36) | 14 (56) |
( |
0 | 0 | 3 (12) | 9 (36) | 13 (52) |
( |
0 | 0 | 4 (16) | 10 (40) | 11 (44) |
( |
0 | 0 | 1 (4) | 11 (42) | 14 (54) |
( |
0 | 1 (4) | 4 (15) | 13 (50) | 8 (31) |
Jill Tinmouth was a lead scientist at Cancer Care Ontario for ColonCancerCheck and paid as a consultant for this work. Catherine Dubé published an editorial in Can J. Gastro 2012 26 417-18 [
The authors would like to thank the following individuals for their assistance in developing this report: (i) Melissa Brouwers, Meghan Hatcher, Sheila McNair, and Hans Messersmith for providing feedback on draft versions, (ii) Waseem Hijazi for conducting a data audit, and (iii) Sara Miller and Jenny Lass for copyediting.