Guaiac-based faecal occult blood tests versus faecal immunochemical tests for colorectal cancer screening in average-risk individuals.

BACKGROUND: Worldwide, many countries have adopted colorectal cancer (CRC) screening programmes, often based on faecal occult blood tests (FOBTs). CRC screening aims to detect advanced neoplasia (AN), which is defined as CRC or advanced adenomas. FOBTs fall into two categories based on detection technique and the detected blood component: qualitative guaiac-based FOBTs (gFOBTs) and faecal immunochemical tests (FITs), which can be qualitative and quantitative. Screening with gFOBTs reduces CRC-related mortality. OBJECTIVES: To compare the diagnostic test accuracy of gFOBT and FIT screening for detecting advanced colorectal neoplasia in average-risk individuals. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, BIOSIS Citation Index, Science Citation Index Expanded, and Google Scholar. We searched the reference lists and PubMed-related articles of included studies to identify additional studies. SELECTION CRITERIA: We included prospective and retrospective studies that provided the number of true positives, false positives, false negatives, and true negatives for gFOBTs, FITs, or both, with colonoscopy as reference standard. We excluded case-control studies. We included studies in which all participants underwent both index test and reference standard ("reference standard: all"), and studies in which only participants with a positive index test underwent the reference standard while participants with a negative test were followed for at least one year for development of interval carcinomas ("reference standard: positive"). The target population consisted of asymptomatic, average-risk individuals undergoing CRC screening. The target conditions were CRC and advanced neoplasia (advanced adenomas and CRC combined). DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies for inclusion. In case of disagreement, a third review author made the final decision. We used the Rutter and Gatsonis hierarchical summary receiver operating characteristic model to explore differences between tests and identify potential sources of heterogeneity, and the bivariate hierarchical model to estimate sensitivity and specificity at common thresholds: 10 µg haemoglobin (Hb)/g faeces and 20 µg Hb/g faeces. We performed indirect comparisons of the accuracy of the two tests and direct comparisons when both index tests were evaluated in the same population. MAIN RESULTS: We ran the initial search on 25 June 2019, which yielded 63 studies for inclusion. We ran a top-up search on 14 September 2021, which yielded one potentially eligible study, currently awaiting classification. We included a total of 33 "reference standard: all" published articles involving 104,640 participants. Six studies evaluated only gFOBTs, 23 studies evaluated only FITs, and four studies included both gFOBTs and FITs. The cut-off for positivity of FITs varied between 2.4 µg and 50 µg Hb/g faeces. For each Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 domain, we assessed risk of bias as high in less than 20% of studies. The summary curve showed that FITs had a higher discriminative ability than gFOBTs for AN (P < 0.001) and CRC (P = 0.004). For the detection of AN, the summary sensitivity of gFOBTs was 15% (95% confidence interval (CI) 12% to 20%), which was significantly lower than FITs at both 10 µg and 20 µg Hb/g cut-offs with summary sensitivities of 33% (95% CI 27% to 40%; P < 0.001) and 26% (95% CI 21% to 31%, P = 0.002), respectively. Results were simulated in a hypothetical cohort of 10,000 screening participants with 1% CRC prevalence and 10% AN prevalence. Out of 1000 participants with AN, gFOBTs missed 850, while FITs missed 670 (10 µg Hb/g cut-off) and 740 (20 µg Hb/g cut-off). No significant differences in summary specificity for AN detection were found between gFOBTs (94%; 95% CI 92% to 96%), and FITs at 10 µg Hb/g cut-off (93%; 95% CI 90% to 95%) and at 20 µg Hb/g cut-off (97%; 95% CI 95% to 98%). So, among 9000 participants without AN, 540 were offered (unnecessary) colonoscopy with gFOBTs compared to 630 (10 µg Hb/g) and 270 (20 µg Hb/g) with FITs. Similarly, for the detection of CRC, the summary sensitivity of gFOBTs, 39% (95% CI 25% to 55%), was significantly lower than FITs at 10 µg and 20 µg Hb/g cut-offs: 76% (95% CI 57% to 88%: P = 0.001) and 65% (95% CI 46% to 80%; P = 0.035), respectively. So, out of 100 participants with CRC, gFOBTs missed 61, and FITs missed 24 (10 µg Hb/g) and 35 (20 µg Hb/g). No significant differences in summary specificity for CRC were found between gFOBTs (94%; 95% CI 91% to 96%), and FITs at the 10 µg Hb/g cut-off (94%; 95% CI 87% to 97%) and 20 µg Hb/g cut-off (96%; 95% CI 91% to 98%). So, out of 9900 participants without CRC, 594 were offered (unnecessary) colonoscopy with gFOBTs versus 594 (10 µg Hb/g) and 396 (20 µg Hb/g) with FITs. In five studies that compared FITs and gFOBTs in the same population, FITs showed a higher discriminative ability for AN than gFOBTs (P = 0.003). We included a total of 30 "reference standard: positive" studies involving 3,664,934 participants. Of these, eight were gFOBT-only studies, 18 were FIT-only studies, and four studies combined both gFOBTs and FITs. The cut-off for positivity of FITs varied between 5 µg to 250 µg Hb/g faeces. For each QUADAS-2 domain, we assessed risk of bias as high in less than 20% of studies. The summary curve showed that FITs had a higher discriminative ability for detecting CRC than gFOBTs (P < 0.001). The summary sensitivity for CRC of gFOBTs, 59% (95% CI 55% to 64%), was significantly lower than FITs at the 10 µg Hb/g cut-off, 89% (95% CI 80% to 95%; P < 0.001) and the 20 µg Hb/g cut-off, 89% (95% CI 85% to 92%; P < 0.001). So, in the hypothetical cohort with 100 participants with CRC, gFOBTs missed 41, while FITs missed 11 (10 µg Hb/g) and 11 (20 µg Hb/g). The summary specificity of gFOBTs was 98% (95% CI 98% to 99%), which was higher than FITs at both 10 µg and 20 µg Hb/g cut-offs: 94% (95% CI 92% to 95%; P < 0.001) and 95% (95% CI 94% to 96%; P < 0.001), respectively. So, out of 9900 participants without CRC, 198 were offered (unnecessary) colonoscopy with gFOBTs compared to 594 (10 µg Hb/g) and 495 (20 µg Hb/g) with FITs. At a specificity of 90% and 95%, FITs had a higher sensitivity than gFOBTs. AUTHORS' CONCLUSIONS: FITs are superior to gFOBTs in detecting AN and CRC in average-risk individuals. Specificity of both tests was similar in "reference standard: all" studies, whereas specificity was significantly higher for gFOBTs than FITs in "reference standard: positive" studies. However, at pre-specified specificities, the sensitivity of FITs was significantly higher than gFOBTs.

Ethical issues in colorectal cancer screening.

In many countries, colorectal cancer screening is currently an established population screening program due to the evidence on its reduction of colorectal cancer mortality. There is general consensus that colorectal cancer screening meets the screening criteria as proposed by Wilson and Jungner. However, as for all population screening programs, colorectal cancer screening also has disadvantages and thereby entails ethical issues. There are the general issues concerning the introduction of screening programs (e.g. medicalization, overdiagnosis and overtreatment, information provision to screenees), evaluation of cancer screening programs (e.g. lead time and length bias), chosen screening method (e.g. false-positive and false-negative test results, reduction of all-cause mortality, choice between different screening methods). The different colorectal cancer screening methods and the ethical issues concerning colorectal cancer screening will be discussed in this review.

The price of autonomy: should we offer individuals a choice of colorectal cancer screening strategies?

A difference between colorectal cancer screening and screening for most other types of cancer is that various screening methods are available. A choice between screening methods is common in the USA. Most European programmes currently offer a single screening method, since it is recommended that only screening strategies with sufficient evidence for a reduction in colorectal cancer mortality are introduced. Faecal occult blood testing is widely accepted in Europe, and evidence on the effectiveness of flexible sigmoidoscopy is increasing. The availability of multiple effective screening options warrants deliberation on whether individuals should be given a choice between strategies. In this Personal View, we present arguments in favour and against offering a choice of screening strategies, together with the evidence substantiating these views. We also focus on screening invitees' autonomy, which is a crucial parameter in the debate.

Performance improvements of stool-based screening tests.

Stool testing is a widely accepted, non-invasive, technique for colorectal cancer (CRC) screening. Guaiac-based faecal occult blood test (gFOBT) screening has been proven to decrease CRC-related mortality; however gFOBT is hampered by a low sensitivity. Faecal immunochemical tests (FITs) have several advantages over gFOBT. First of all, FIT has a better sensitivity and higher uptake. Furthermore, the quantitative variant of the FIT allows choices on cut-off level for test-positivity according to colonoscopy resources available, personal risk profile, and/or intended detection rate in the screened population. Stool-based DNA (sDNA) tests aiming at the detection of specific DNA alterations may improve detection of CRC and adenomas compared to gFOBT screening, but large-scale population based studies are lacking. This review focuses on factors influencing test performance of those three stool based screening tests.

Labeled versus unlabeled discrete choice experiments in health economics: an application to colorectal cancer screening.

OBJECTIVES: Discrete choice experiments (DCEs) in health economics commonly present choice sets in an unlabeled form. Labeled choice sets are less abstract and may increase the validity of the results. We empirically compared the feasibility, respondents' trading behavior, and convergent validity between a labeled and an unlabeled DCE for colorectal cancer (CRC) screening programs in The Netherlands. METHODS: A labeled DCE version presented CRC screening test alternatives as "fecal occult blood test,""sigmoidoscopy," and "colonoscopy," whereas the unlabeled DCE version presented them as "screening test A" and "screening test B." Questionnaires were sent to participants and nonparticipants in CRC screening. RESULTS: Total response rate was 276 (39%) out of 712 and 1033 (46%) out of 2267 for unlabeled and labeled DCEs, respectively (P<0.001). The labels played a significant role in individual choices; approximately 22% of subjects had dominant preferences for screening test labels. The convergent validity was modest to low (participants in CRC screening: r=0.54; P=0.01; nonparticipants: r=0.17; P=0.45) largely because of different preferences for screening frequency. CONCLUSION: This study provides important insights in the feasibility and difference in results from labeled and unlabeled DCEs. The inclusion of labels appeared to play a significant role in individual choices but reduced the attention respondents give to the attributes. As a result, unlabeled DCEs may be more suitable to investigate trade-offs between attributes and for respondents who do not have familiarity with the alternative labels, whereas labeled DCEs may be more suitable to explain real-life choices such as uptake of cancer screening.