Colorectal Cancer Screening by Fecal Immunochemical Tests (FIT): Considerations on Sampling and Markers (Hb and Hb/Hp Complex) of Fecal Occult Blood (FOB).

BACKGROUND/AIM: Formal demonstration of the efficacy of colorectal cancer (CRC) screening by fecal immunochemical tests (FITs) in reducing CRC incidence and mortality is still missing. The aim of this study was to analyze the impact of sampling and FIT marker in the recently implemented CRC screening program in Finland. PATIENTS AND METHODS: Because only the index test [FIT hemoglobin (Hb)]-positive subjects are verified by the reference test (colonoscopy), the new screening program is subject to verification bias that precludes estimating the diagnostic accuracy (DA) indicators. A previously published study (5) with 100% biopsy verification of colonoscopy referral subjects (called validation cohort, n=300) was used to derive these missing DA estimates. Two points of concern were addressed: i) only one-day sample tested, and ii) only the Hb component (but not Hb/Hp complex) was analyzed by FIT. RESULTS: The estimated DA of one-sample testing for Hb in the screening setting had a very low sensitivity (SE) (12.5%; 95%CI=12.3-12.7) for adenomas, with AUC=0.560 (for CRC, AUC=0.950). Testing three samples for Hb improved SE to 19.4% (95%CI=19.1-19.7%) but had little effect on overall DA (AUC=0.590). For adenomas, one-sample testing for Hb and Hb/Hp complex provided higher SE than three-sample testing for Hb (SE 20.6%; 95%CI=20.3-21.0), and the best SE was reached when two samples were tested for Hb and Hb/Hp complex (SE 47.5%; 95%CI=46.9-48.1%) (AUC=0.730). CONCLUSION: The strategy of the current CRC screening could be significantly improved by testing two consecutive samples by Hb and Hb/Hp complex, instead of stand-alone Hb testing of one sample.

The association between organised colorectal cancer screening strategies and reduction of its related mortality: a systematic review and meta-analysis.

BACKGROUND: To assess the long-term association between organised colorectal cancer (CRC) screening strategies and CRC-relate mortality. METHODS: We systematically reviewed studies on organised CRC screening through PubMed, Ovid Medline, Embase and Cochrane from the inception. We retrieved characteristics of organised CRC screening from included literature and matched mortality (over 50 years) of those areas from the International Agency for Research on Cancer in May 2023. The variations of mortality were reported via the age-standardised mortality ratio. A random-effects model was used to synthesis results. RESULTS: We summarised 58 organised CRC screening programmes and recorded > 2.7 million CRC-related deaths from 22 countries where rollout screening programmes were performed. The CRC screening strategy with faecal tests (guaiac faecal occult blood test (gFOBT) or faecal immunochemical tests (FIT)) or colonoscopy as the primary screening offer was associated with a 41.8% reduction in mortality, which was higher than those offered gFOBT (4.4%), FIT (16.7%), gFOBT or FIT (16.2%), and faecal tests (gFOBT or FIT) or flexible sigmoidoscopy (16.7%) as primary screening test. The longer duration of screening was associated with a higher reduction in the pooled age-standardised mortality ratio. In particular, the pooled age-standardised mortality ratio became non-significant when the screening of FIT was implemented for less than 5 years. CONCLUSIONS: A CRC screening programme running for > 5 years was associated with a reduction of CRC-related mortality. Countries with a heavy burden of CRC should implement sustainable, organised screening providing a choice between faecal tests and colonoscopy as a preferred primary test.

Post-colonoscopy colorectal cancer: A population-based cohort study of fecal occult blood test-positive colonoscopies.

BACKGROUND: Data on post-colonoscopy colorectal cancers (PCCRCs) after fecal occult blood test (FOBT)-positive colonoscopies is scarce (guaiac-based (gFOBT) or fecal immunochemical test (FIT)). AIMS: Evaluate the prevalence and characteristics of PCCRCs in the French gFOBT CRC screening program. METHODS: Retrospective population-based cohort study of all gFOBT-positive colonoscopies performed among individuals aged 50-74 between 2003 and 2014 within the CRC screening program organized in the Haut-Rhin (Alsace, France). The main outcome was PCCRC-3y rate. Adenoma detection rates (ADRs) calculated on gFOBT-positive colonoscopies were compared to those calculated on FIT-positive colonoscopies performed by the same gastroenterologists. RESULTS: Overall, 9106 gFOBT-positive colonoscopies performed by 36 gastroenterologists were included. Sixteen PCCRC-3y and 31 PCCRC-5y were diagnosed (68.8 % and 58.1 % were true interval PCCRCs respectively). The unadjusted PCCRC-3y rate was 2.4 % [95 % confidence interval (CI) 1.4 %-3.9 %]. The risk for PCCRC-5y was significantly higher when the gastroenterologist's ADR was <35 % compared to ≥35 % (HR 2.17 [95 %CI 1.19-3.93]). The mean absolute difference for ADR between gFOBT- and FIT-positive colonoscopies was 16.3 % in favor of FIT-positive colonoscopies. CONCLUSION: PCCRC-3y prevalence was low, estimated at 2.4 %. We suggest that the minimum standard for ADR in gFOBT- and FIT-positive colonoscopies should be set at 35 % and 50 % to 55 % respectively, in the French screening program.

Interval cancers in a national colorectal screening programme based on faecal immunochemical testing: Implications for faecal haemoglobin concentration threshold and sex inequality.

OBJECTIVE: To compare interval cancer proportions (ICP) in the faecal immunochemical test (FIT)-based Scottish Bowel Screening Programme (SBoSP) with the former guaiac faecal occult blood test (gFOBT)-based SBoSP and investigate associations between interval cancer (IC) and faecal haemoglobin concentration (f-Hb) threshold, sex, age, deprivation, site, and stage. METHODS: The ICP data from first year of the FIT-based SBoSP and the penultimate year of the gFOBT-based SBoSP were compared in a prospective cohort design. RESULTS: With FIT, 801 colorectal cancers (CRCs) were screen detected (SDC), 802 were in non-participants, 548 were ICs, 39 were colonoscopy missed and 72 were diagnosed after incomplete screening; with gFOBT: 540, 904, 556, 45, and 13, respectively. FIT had a significantly higher proportion of SDC compared to IC than gFOBT. For FIT and gFOBT, ICP was significantly higher in women than men. As f-Hb threshold increased, ICP increased and, for any f-Hb threshold for men, a lower threshold was required for comparable ICP in women. In Scotland, the current threshold of ≥80 µg Hb/g faeces would have to be lowered to ≥40 µg Hb/g faeces for women to achieve sex equality for ICP. In the FIT-based SBoSP, there were four times as many stage I SDC than IC. This was reversed in advanced stages, with twice as many stage IV CRC diagnosed as IC versus SDC. CONCLUSIONS: Reducing the numbers of IC requires lowering the f-Hb threshold. Using different f-Hb thresholds for women and men could eliminate the sex disparity, but with additional colonoscopy.

The Non-Invasive Prediction of Colorectal Neoplasia (NIPCON) Study 1995-2022: A Comparison of Guaiac-Based Fecal Occult Blood Test (FOBT) and an Anti-Adenoma Antibody, Adnab-9.

Given the need to improve the sensitivity of non-invasive methods to detect colorectal neoplasia, particularly adenomas, we compared a fecal test using a monoclonal antibody (Mab) raised against constituents of colonic adenomas designated Adnab-9 (Adenoma Antibody 9), recognizing an N-linked 87 kDa glycoprotein, to gFOBT, which is shown to reduce CRC mortality. p87 immunohistochemistry testing is significantly more sensitive (OR 3.64[CI 2.37-5.58]) than gFOBT (guaiac-based fecal occult blood test) for adenomas (<3 in number), advanced adenomas (OR 4.21[CI 2.47-7.15]), or a combination of the two (OR 3.35[CI 2.47-4.53]). p87 immunohistochemistry shows regional Paneth cell (PC) expression mainly in the right-sided colon and is significantly reduced in the ceca of African Americans (p < 0.0001). In a subset of patients, we obtained other body fluids such as urine, colonic effluent, and saliva. Urine tests (organ-specific neoantigen) showed a significant difference for advanced adenomas (p < 0.047). We conclude that fecal p87 testing is more sensitive than gFOBT and Adnab-9 and could be used to better direct the colonoscopy screening effort.

Stool DNA testing for early detection of colorectal cancer: systematic review using the HTA Core Model® for Rapid Relative Effectiveness Assessment.

Background: Stool DNA testing for early detection of colorectal cancer (CRC) is a non-invasive technology with the potential to supplement established CRC screening tests. The aim of this health technology assessment was to evaluate effectiveness and safety of currently CE-marked stool DNA tests, compared to other CRC tests in CRC screening strategies in an asymptomatic screening population. Methods: The assessment was carried out following the guidelines of the European Network for Health Technology Assessment (EUnetHTA). This included a systematic literature search in MED-LINE, Cochrane and EMBASE in 2018. Manufacturers were asked to provide additional data. Five patient interviews helped assessing potential ethical or social aspects and patients' experiences and preferences. We assessed the risk of bias using QUADAS-2, and the quality of the body of evidence using GRADE. Results: We identified three test accuracy studies, two of which investigated a multitarget stool DNA test (Cologuard®, compared fecal immunochemical test (FIT)) and one a combined DNA stool assay (ColoAlert®, compared to guaiac-based fecal occult blood test (gFOBT), Pyruvate Kinase Isoenzyme Type M2 (M2-PK) and combined gFOBT/M2-PK). We found five published surveys on patient satisfaction. No primary study investigating screening effects on CRC incidence or on overall mortality was found. Both stool DNA tests showed in direct comparison higher sensitivity for the detection of CRC and (advanced) adenoma compared to FIT, or gFOBT, respectively, but had lower specificity. However, these comparative results may depend on the exact type of FIT used. The reported test failure rates were higher for stool DNA testing than for FIT. The certainty of evidence was moderate to high for Cologuard® studies, and low to very low for the ColoAlert® study which refers to a former version of the product and yielded no direct evidence on the test accuracy for ad-vanced versus non-advanced adenoma. Conclusions: ColoAlert® is the only stool DNA test currently sold in Europe and is available at a lower price than Cologuard®, but reliable evidence is lacking. A screening study including the current product version of ColoAlert® and suitable comparators would, therefore, help evaluate the effectiveness of this screening option in a European context.

Healthcare costs, resource utilization, and productivity loss associated with colorectal cancer screening.

OBJECTIVES: To evaluate healthcare costs, resource utilization, associated costs, and lost productivity for colorectal cancer (CRC) screening in an average-risk population. METHODS: This retrospective cohort study identified average-risk individuals (50-75 years) with claims in the Optum Research Database for CRC screening test between 1 January 2014 to 31 December 2018. Index date was defined as the first date of a claim for colonoscopy, fecal immunochemical test (FIT), guaiac-based fecal occult blood test (FOBT) or multi-target stool DNA test (mt-sDNA). Screening costs were evaluated with descriptive statistics and multivariable analyses, adjusting for patient characteristics and index screening costs. RESULTS: In total, 903,831 individuals were identified by test groups: mt-sDNA (n = 29,614), FIT (n = 254,002), guaiac-based FOBT (n = 112,757) and colonoscopy (n = 507,458). Adjusted costs for index screening were, colonoscopy ($3,029), mt-sDNA ($752), FIT ($45), and (FOBT ($153). Adjusted costs across the six months following the index screening were $146 for colonoscopy, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. CONCLUSIONS: Screening colonoscopy had the highest productivity loss and healthcare costs up-front, suggesting potential cost benefits for noninvasive screening modalities. The more frequent screening interval required for FIT and FOBT resulted in a higher yearly cost than colonoscopy or mt-sDNA.

Colorectal cancer (CRC) is a prominent healthcare concern the United States, which accounted for 149,500 new cases and 52,980 deaths in 2021. Screening is effective for diagnosing the condition at earlier more treatable stages, and reducing deaths. However, screening is largely underutilized in part due to perceived cost barriers. This observational study used insurance claims data to calculate healthcare costs, resource use, and lost productivity for CRC screening in an average-risk population aged 50­75 years. A total of 903,831 individuals were identified by test groups: multi-target stool DNA test (mt-sDNA test; 29,614 individuals), fecal immunochemical test (FIT; 254,002 individuals), guaiac-based fecal occult blood test (FOBT; 112,757 individuals) and colonoscopy (507,458 individuals). Adjusted costs for initial screening were $3,029 for colonoscopy, $752 for mt-sDNA, $45 for FIT, and $153 for FOBT. Adjusted colonoscopy-related costs combined across the six months following the initial screening were $146 for the colonoscopy cohort, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. Overall, screening colonoscopy was accompanied by the highest productivity loss and up-front costs, suggesting potential cost benefits for noninvasive screening modalities ­ mt-sDNA, FIT, and FOBT; however, the more frequent screening interval required by FIT and FOBT resulted in a higher estimated average yearly screening cost.

Supply and quality of colonoscopy according to the characteristics of gastroenterologists in the French population-based colorectal-cancer screening program.

BACKGROUND: Since its complete roll-out in 2009, the French colorectal cancer screening program (CRCSP) experienced 3 major constraints [use of a less efficient Guaiac-test (gFOBT), stopping the supply of Fecal-Immunochemical-Test kits (FIT), and suspension of the program due to the coronavirus disease 2019 (COVID-19)] affecting its effectiveness. AIM: To describe the impact of the constraints in terms of changes in the quality of screening-colonoscopy (Quali-Colo). METHODS: This retrospective cohort study included screening-colonoscopies performed by gastroenterologists between Jan-2010 and Dec-2020 in people aged 50-74 living in Ile-de-France (France). The changes in Quali-colo (Proportion of colonoscopies performed beyond 7 mo (Colo_7 mo), Frequency of serious adverse events (SAE) and Colonoscopy detection rate) were described in a cohort of Gastroenterologists who performed at least one colonoscopy over each of the four periods defined according to the chronology of the constraints [gFOBT: Normal progress of the CRCSP using gFOBT (2010-2014); FIT: Normal progress of the CRCSP using FIT (2015-2018); STOP-FIT: Year (2019) during which the CRCSP experienced the cessation of the supply of test kits; COVID: Program suspension due to the COVID-19 health crisis (2020)]. The link between each dependent variable (Colo_7 mo; SAE occurrence, neoplasm detection rate) and the predictive factors was analyzed in a two-level multivariate hierarchical model. RESULTS: The 533 gastroenterologists (cohort) achieved 21509 screening colonoscopies over gFOBT period, 38352 over FIT, 7342 over STOP-FIT and 7995 over COVID period. The frequency of SAE did not change between periods (gFOBT: 0.3%; FIT: 0.3%; STOP-FIT: 0.3%; and COVID: 0.2%; P = 0.10). The risk of Colo_7 mo doubled between FIT [adjusted odds ratio (aOR): 1.2 (1.1; 1.2)] and STOP-FIT [aOR: 2.4 (2.1; 2.6)]; then, decreased by 40% between STOP-FIT and COVID [aOR: 2.0 (1.8; 2.2)]. Regardless of the period, this Colo_7 mo's risk was twice as high for screening colonoscopy performed in a public hospital [aOR: 2.1 (1.3; 3.6)] compared to screening-colonoscopy performed in a private clinic. The neoplasm detection, which increased by 60% between gFOBT and FIT [aOR: 1.6 (1.5; 1.7)], decreased by 40% between FIT and COVID [aOR: 1.1 (1.0; 1.3)]. CONCLUSION: The constraints likely affected the time-to-colonoscopy as well as the colonoscopy detection rate without impacting the SAE's occurrence, highlighting the need for a respectable reference time-to-colonoscopy in CRCSP.

“[... ] ad agritudinem podagram [... ]”: sobre el empleo del guayaco en los comienzos del siglo XVI / “[... ] ad agritudinem podagram [... ]”: on the use of guaiac at the beginning of the 16th century

En los últimos años se ha abordado el estudio de distintas prescripciones y consejos dietéticos en lenguas vernáculas de personajes vinculados a las élites castellanas, catalanas y navarras, datados entre la segunda mitad del siglo XV y finales del XVI. Uno de los personajes estudiados es el clérigo Juan Rena, veneciano de origen, que desde principios del siglo XVI ocupó puestos de responsabilidad en la administración castellana. Nombrado capellán de la reina Juana I de Castilla en 1508, fue Rena la ‘mano derecha’ de Fernando II de Aragón en la restructuración administrativa del reino de Navarra tras su conquista en 1512. Entre la nume-rosa documentación relacionada con su persona se han localizado dos textos para tratar la gota, basado en un ingrediente procedente del Nuevo Mundo, el palosanto o guayaco, en un periodo relativamente temprano. (AU)

Incident colorectal cancer screening and associated healthcare resource utilization and Medicare cost among Medicare beneficiaries aged 66-75 years in 2016-2018.

BACKGROUND: While prevalence of up-to-date screening status is the usual reported statistic, annual screening incidence may better reflect current clinical practices and is more actionable. Our main purpose was to examine incident colorectal cancer (CRC) screening rates in Medicare beneficiaries and to explore characteristics associated with CRC screening. METHODS: Using 20% Medicare random sample data, the study population included 2016-2018 Medicare fee-for-service beneficiaries covered by Parts A and B aged 66-75 years at average CRC risk. For each study year, we excluded individuals who had a Medicare claim for a colonoscopy within 9 years, flexible sigmoidoscopy within 4 years, and multitarget stool DNA test (mt-sDNA) within 2 years prior; therefore, any observed screening during study year was considered an "incident screening". Incident screening rates were calculated as number of incident screenings per 1000 Medicare beneficiaries. Overall rates were normalized to 2018 Medicare population distributions of age, sex, and race. RESULTS: Each year, > 1.4 million individuals met the inclusion/exclusion criteria from > 6.5 million Medicare beneficiaries. The overall adjusted incident CRC screening rate per 1000 Medicare beneficiaries increased from 85.2 in 2016 to 94.3 in 2018. Incident screening rates decreased 11.4% (22.9 to 20.3) for colonoscopy and 2.4% (58.3 to 56.9) for fecal immunochemical test/guaiac-based fecal occult blood test; they increased 201.5% (6.5 to 19.6) for mt-sDNA. The 2018 unadjusted rate was 76.0 for men and 110.4 for women. By race/ethnicity, the highest 2018 rate was for Asian individuals and the lowest rate was for Black individuals (113.4 and 72.8, respectively). CONCLUSIONS: The 2016-2018 observed incident CRC screening rate in average-risk Medicare beneficiaries, while increasing, was still low. Our findings suggest more work is needed to improve CRC screening overall and, especially, among male and Black Medicare beneficiaries.

Do faecal test-based colorectal cancer screening pilots provide data that are reflected in subsequent programmes? Evidence from interval cancer proportions.

OBJECTIVE: Guidelines on colorectal cancer (CRC) screening with guaiac faecal occult blood tests (gFOBTs) and faecal immunochemical tests (FITs) include the need for a pilot before a programme is introduced. Interval cancers (ICs), cancers arising after a negative screening test result but before the next scheduled invite, are important indicators of programme quality. Our aim was to compare IC in the gFOBT-based Scottish Bowel Screening Programme (SBoSP), a FIT-based pilot, and the FIT-based SBoSP, to assess if the pilot provided data that was reflected in the subsequent programme. DESIGN: The IC proportions (ICPs) data ([IC/(IC + screen detected CRC)] x 100) from the penultimate year of the gFOBT-based SBoSP, the 6-month pilot and the first year of the FIT-based SBoSP were compared. To ensure appropriate comparison, these data were only from the two pilot NHS Boards. RESULTS: For all participants, and females and males, the ICPs were very similar in the gFOBT-based SBoSP and the pilot. The faecal haemoglobin concentration (f-Hb) threshold for the pilot was set at ≥80 µg Hb/g faeces. However, in marked contrast, in the FIT-based SBoSP, at the same threshold, the ICPs were lower. In all three groups, the ICPs were higher in females than in males. CONCLUSIONS: Data on variables in pilots, including ICP, can be informative, but only if variables such as FIT system are held consistent between pilot and programme. Lowering the f-Hb threshold for females to give the same ICP as males might be a strategy to minimise sex inequality.

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.

Optimizing the Design of a Repeated Fecal Immunochemical Test Bowel Cancer Screening Programme With a Limited Endoscopy Capacity From a Health Economic Perspective.

OBJECTIVES: In 2016, it was announced that the fecal immunochemical test (FIT) would replace the guaiac fecal occult blood test in the UK Bowel Cancer Screening Programme. England has limited endoscopy capacity. This study informed decision making by determining the most cost-effective FIT screening strategy (age range, frequency, and FIT threshold) under a constrained endoscopy capacity. METHODS: An economic model with a colorectal cancer natural history component was used to model 60 221 screening strategies with first screening at age 50 to 60 years, screening interval of 1 to 6 years, 3+ screening episodes, and FIT integer threshold of 20 to 180 µg hemoglobin/g feces. Screening strategies requiring the same endoscopy capacity were compared to determine the characteristics of the most cost-effective strategies. RESULTS: With 50 000 annual screening referral colonoscopies, the 20 most cost-effective strategies had a starting age of 50 to 53 years, 2-yearly screening, 7 or 8 rounds of screening, and FIT threshold of 127 to 166. Compared with a 2-yearly screening interval, screening less frequently (3-, 4-, 5-, or 6-yearly) with a more sensitive FIT was less cost-effective. CONCLUSIONS: The UK Bowel Cancer Screening Programme should use a 2-yearly FIT screening interval. When endoscopy capacity increases, the screening starting age should be reduced first followed by reducing the FIT threshold. These findings are relevant for other colorectal cancer screening programs with constrained endoscopy capacity.

Benefit of Biennial Fecal Occult Blood Screening on Colorectal Cancer in England: A Population-Based Case-Control Study.

BACKGROUND: The English national bowel cancer screening program offering a guaiac fecal occult blood test began in July 2006. In randomized controlled trials of guaiac fecal occult blood test screening, reductions in mortality were accompanied by reductions in advanced stage colorectal cancer (CRC). We aimed to evaluate the effect of participation in the national bowel cancer screening program on stage-specific CRC incidence as a likely precursor of a mortality effect. METHODS: In this population-based case-control study, cases were individuals diagnosed with CRC aged 60-79 years between January 1, 2012, and December 31, 2013. Two controls per case were matched on geographic region, gender, date of birth, and year of first screening invitation. Screening histories were extracted from the screening database. Conditional logistic regression with correction for self-selection bias was used to estimate odds ratios (odds ratios corrected for self-selection bias [cOR]) and 95% confidence intervals (CIs) by Duke stage, sex, and age. RESULTS: 14 636 individuals with CRC and 29 036 without were eligible for analysis. The odds of CRC (any stage) were increased within 30 days of a screening test and decreased thereafter. No reduction in CRC (any stage) among screened individuals compared with those not screened was observed (cOR = 1.00, 95% CI = 0.89 to 1.15). However, screened individuals had lower odds of Duke stage D CRC (cOR = 0.68, 95% CI = 0.50 to 0.93). We estimate 435 fewer Duke D CRC by age 80 years in 100 000 people screened biennially between ages 60 and 74 years compared with an unscreened cohort. CONCLUSION: The impact of colorectal screening on advanced CRC incidence suggests that the program will meet its aim of reducing mortality.

The ColonView (CV) Quick Test for Fecal Occult Blood Shows Significantly Higher Diagnostic Accuracy in Detecting Distal than Proximal Colorectal Cancer.

AIM: The present study compared the accuracy of ColonView (CV) quick test in detecting proximal versus distal colorectal cancer (CRC). A traditional guaiac-based fecal occult blood test (gFOBT) (Hemoccult SENSA) was used as a reference. PATIENTS AND METHODS: A cohort of 368 colonoscopy-referral patients were asked to collect 3 consecutive fecal samples, to be analyzed by both assays (CV, SENSA). Receiver operating characteristic (ROC) analysis was used to find the optimal cut-off values for both Hb and Hb/Hp of the CV test. Summary hierarchical ROC (HSROC) curves were used to visualize the pooled overall accuracy of visually analysed (VA) and automatically analyzed (AA) reading modes in proximal and distal CRC detection. RESULTS: The overall specificity (Sp) of the AA reading mode for the proximal CRC and distal CRC endpoint was 73% and 76%, respectively. For proximal CRC, the two most sensitive AA tests showed 90% sensitivity (Se), while for distal CRC, the two most sensitive AA tests showed 100% Se. In the HSROC analysis, the AUC values were as follows: i) VA in proximal CRC: 0.765, ii) AA in proximal CRC: 0.878, iii) VA in distal CRC: 0.955 and iv) AA in distal CRC: 0.961. In roccomp analysis, AUC values were significantly different in: VA vs. AA in proximal CRC p=0.009; VA in proximal vs. VA in distal CRC p<0.0001; VA in proximal vs. AA in distal CRC p<0.0001; AA in proximal vs. VA in distal CRC p=0.021; AA in proximal CRC vs. AA in distal CRC p=0.006. CONCLUSION: The applicability of the CV test (a new-generation FIT) in CRC screening was confirmed. The AA reading was superior to VA (or SENSA) in its diagnostic accuracy in detecting proximal CRC patients. Distal CRCs were more accurately detected than proximal CRCs by both reading modes.

Colonoscopy-Related Adverse Events in Patients With Abnormal Stool-Based Tests: A Systematic Review of Literature and Meta-analysis of Outcomes.

INTRODUCTION: Colorectal cancer (CRC) screening programs based on the fecal immunochemical test (FIT) and guaiac-based fecal occult blood (gFOBT) are associated with a substantial reduction in CRC incidence and mortality. We conducted a systematic review and comprehensive meta-analysis to evaluate colonoscopy-related adverse events in individuals with a positive FIT or gFOBT. METHODS: A systematic and detailed search was run in January 2021, with the assistance of a medical librarian for studies reporting on colonoscopy-related adverse events as part of organized CRC screening programs. Meta-analysis was performed using the random-effects model, and the results were expressed for pooled proportions along with relevant 95% confidence intervals (CIs). RESULTS: A total of 771,730 colonoscopies were performed in patients undergoing CRC screening using either gFOBT or FIT across 31 studies. The overall pooled incidence of severe adverse events in the entire patient cohort was 0.42% (CI 0.20-0.64); I2 = 38.76%. In patients with abnormal gFOBT, the incidence was 0.2% (CI 0.1-0.3); I2 = 24.6%, and in patients with a positive FIT, it was 0.4% (CI 0.2-0.7); I2 = 48.89%. The overall pooled incidence of perforation, bleeding, and death was 0.13% (CI 0.09-0.21); I2 = 22.84%, 0.3% (CI 0.2-0.4); I2 = 35.58%, and 0.01% (CI 0.00-0.01); I2 = 33.21%, respectively. DISCUSSION: Our analysis shows that in colonoscopies performed after abnormal stool-based testing, the overall risk of severe adverse events, perforation, bleeding, and death is minimal.

[Fecal occult blood test for colorectal cancer screening]. / Test de sangre oculta en deposiciones para programas de cribado de cáncer colorrectal: actualización.

Screening programs for colorectal cancer (CRC) are standard in most developed countries because they reduce mortality and are cost-effective. Within them, colonoscopy allows to directly visualize the colon and remove neoplastic lesions. However, it is an expensive exam with low adherence in asymptomatic individuals. The fecal occult blood test (FOBT) is a low-cost and risk-free method for the user, which results in a high rate of adherence, explaining its use in most screening programs. This article analyzes the effectiveness of different fecal occult blood tests in screening programs. The main conclusions are that the sensitivity of the guaiac-based chemical test for the detection of colorectal cancer is lower than that observed with qualitative and quantitative immunological tests. Automated quantitative methods allow objective readings independent of the operator and the reaction reading time, necessary for the analysis of large numbers of samples. The participation rate with immunological FOBTs is higher than with chemical ones, which is why they are preferred by the different countries that have screening programs. The use of quantitative tests allows stratification of symptomatic and asymptomatic patients at higher risk, in the screening programs.

Significant decrease in interval colorectal cancer incidence after implementing immunochemical testing in a multiple-round guaiac-based screening programme.

BACKGROUND AND AIMS: We aimed to evaluate the effects of switching to faecal immunochemical testing (FIT) on the cumulative 2-year incidence rate of interval cancers, interval cancer rate and test sensitivity within a mature population-based colorectal cancer screening programme consisting of six rounds of biennial guaiac faecal occult blood testing (gFOBT). METHODS: The FIT results were compared with those of gFOBT used in each of the previous two rounds. For the three rounds analysed, 279,041 tests were performed by 156,186 individuals. Logistic regression analysis was used to determine interval cancer risk factors (Poisson regression) and to compare the sensitivity of FIT to gFOBT. RESULTS: There were 612 cases of screen-detected cancers and 209 cases of interval cancers. The sex- and age-adjusted cumulative 2-year incidence rates of interval cancers were 55.7 (95% CI, 45.3-68.5), 42.4 (95% CI, 32.6-55.2) and 15.8 (95% CI, 10.9-22.8) per 100,000 person-years after the last two rounds of gFOBT and FIT, respectively. The FIT/gFOBT incidence rate ratio was 0.38 [95% CI, 0.27-0.54] (P < 0.001). Sex- and age-adjusted sensitivity was significantly higher with FIT than with gFOBT (OR = 6.70 [95% CI, 4.48-10.01], P < 0.0001). CONCLUSIONS: This population-based study revealed a dramatic decrease in the cumulative incidence rates of interval cancers after switching from gFOBT to FIT. These data provide an additional incentive for countries still using gFOBT to switch to FIT.