Divergent detection rates of fecal immunochemical test and questionnaire-based risk assessment for detecting proximal and distal advanced colorectal adenomas

Quantitation of Hemoglobin Improves Fecal Immunochemical Tests for Noninvasive Screening

Endoscopist Characteristics and Polyp Detection in Colonoscopy: Cross-Sectional Analyses of Screening of Swedish Colons

Is this the end of colonoscopy screening for colorectal cancer? An Asia-Pacific perspective.

Colorectal cancer (CRC) screening has come of age in Canada, with every province now having a screening program either implemented or well underway. These programs are based on the detection of fecal occult blood, with positive results triggering colonoscopy for definitive diagnosis. This approach is supported by high-level evidence demonstrating a mortality benefit for individuals screened in this manner. Fecal occult blood testing (FOBT) uses indirect methods to test for
\nthe presence of hemoglobin, which can be affected by chemicals, such as vitamin C, or heme from other sources such as red meat. In contrast, fecal immunochemical tests (FIT) use an antibody to detect human globin directly. These assays may offer advantages of greater specificity
\nand sensitivity, and improved adherence. Most FITs produce a visual colour change on a strip to indicate a positive result, but some are analyzed using automated systems in a laboratory to provide a quantitative result.

The comparative effectiveness of sigmoidoscopy and fecal immunochemical testing (FIT) for colorectal cancer (CRC) screening is unknown. Individuals aged 50-74 years living in Southeast Norway were randomly invited between 2012 and 2019 to either once-only flexible sigmoidoscopy or FIT screening every second year. Colonoscopy was recommended after sigmoidoscopy if any polyp of ≥10 mm, ≥3 adenomas, any advanced adenomas, or CRC was found or, subsequent to, FIT >15 μg hemoglobin/g feces. Data for this report were obtained after complete recruitment in both groups and included 2 full FIT rounds and part of the third round. Outcome measures were participation, neoplasia detection, and adverse events. Age-standardized detection rates and age-adjusted odds ratios (ORs) were calculated. We included 139,291 individuals: 69,195 randomized to sigmoidoscopy and 70,096 to FIT. The participation rate was 52% for sigmoidoscopy, 58% in the first FIT round, and 68% for 3 cumulative FIT rounds. Compared to sigmoidoscopy, the detection rate for CRC was similar in the first FIT round (0.25% vs 0.27%; OR, 0.92; 95% confidence interval [CI], 0.75-1.13) but higher after 3 FIT rounds (0.49% vs 0.27%; OR, 1.87; 95% CI, 1.54-2.27). Advanced adenoma detection rate was lower in the first FIT round compared to sigmoidoscopy at 1.4% vs 2.4% (OR, 0.57; 95% CI, 0.53-0.62) but higher after 3 cumulative FIT rounds at 2.7% vs 2.4% (OR, 1.14; 95% CI, 1.05-1.23). There were 33 (0.05%) serious adverse events in the sigmoidoscopy group compared to 47 (0.07%) in the FIT group (P = .13). Participation was higher and more CRC and advanced adenomas were detected with repeated FIT compared to sigmoidoscopy. The risk of perforation and bleeding was comparable. Clinicaltrials.gov, Number: NCT01538550.

Screening and Surveillance Colonoscopy and COVID-19: Avoiding More Casualties

The objectives of this session are to: 1) review the new guidelines for average-risk colorectal cancer (CRC) screening; 2) review recent selected studies of CRC screening for currently recommended tests, and; 3) review recent decision analyses and a cost-effectiveness analysis on screening. Guidelines: Less than 2 years ago, colorectal cancer (CRC) screening guidelines were highly concordant and flexible. New guidelines issued by the American Cancer Society/American College of Radiology/Multisociety Task Force in March 2008 (1), the U.S. Preventive Services Task Force in November 2008 (2) and the American College of Gastroenterology in March 2009 (3) are now disparate, with two of three organizations implicitly or explicitly preferring colonoscopy despite the absence of published evidence supporting this preference. Two decision analyses, commissioned by the USPSTF, show four screening strategies with equivalence in CRC mortality reduction and life-years gained: colonoscopy every 10 years; a sensitive guaiac-based fecal occult blood test (FOBT) annually; fecal immunochemical testing (FIT) annually, and; the combination of flexible sigmoidoscopy every 5 years with a mid-interval sensitive FOBT or FIT. (4) Screening tests: For fecal DNA, a large screening study comparing a multi-component panel to Hemoccult II with colonoscopy as the reference standard showed that fecal DNA detected 52% of CRCs compared to 13% for Hemoccult II; the two tests had comparable specificity. Recent case-control studies of fecal DNA using somewhat different markers show a single application cancer sensitivity of 83–88% and specificity of 82%.(5) Yet another version of fecal DNA showed cancer sensitivity and specificity of 58% and 84%, respectively; sensitivity for adenomas 1 cm or larger was 46%.(6) The main issues limiting wider use of fecal DNA are its uncertain test interval and greater cost compared to other non-invasive tests. Computer tomographic colonography (CTC or “virtual colonoscopy”) continues to demonstrate good-to-excellent test characteristics for CRC and large (1 cm or larger) adenomas. The ACRIN trial reaffirmed CTC's test characteristics, and may have enhanced prospects for generalizability of test performance. (7) Ongoing issues for CTC include deciding on which CTC colonic findings should be reported and which should lead to colonoscopy (polyp size, number); radiation dose; the clinical and economic impact of extracolonic findings; cost-effectiveness of CTC; and whether it would increase population adherence to CRC screening. Immunochemical FOBTs (or FITs) were developed to enhance the test characteristics of guaiac-based tests. FITs use monoclonal or polyclonal antibodies to detect the intact portion of human hemoglobin and are specific for occult bleeding from a lower GI source. Several FITs are currently available for CRC screening as qualitative tests. Few studies of FITs use colonoscopy as a reference standard; the few that do show widely varying test characteristics for cancer and advanced adenomas, although these are generally better than those of guaiac-based FOBTs. (8) Studies comparing guaiac-based FOBTs with FITs show higher acceptance rates as well as higher detection rates for cancer and advanced adenomas. (9) The real potential of FITs may be in their use as quantitative tests, as data from Levi and colleagues (10) suggest, although more investigation is required to determine the optimal number of single-application tests and the threshold for a positive test. A recent cost-effectiveness analysis by Parekh and colleagues (11) suggests that, as CRC treatment costs increase, screening with FIT may be cost-saving. This analysis also showed that annually FIT screening dominated colonoscopy screening every ten years, meaning that it was both less costly and more effective, suggesting that annual FIT may be “better than” colonoscopy when FIT adherence is high. Until just a few months ago, the effectiveness of sigmoidoscopy was supported only by high-quality case-control studies. Seven-year interim findings from NORCCAP, one of 4 ongoing trials of sigmoidoscopy, were published earlier this year. (12) Study findings included no difference in cancer incidence (not unexpected given the relatively short follow-up); no difference in CRC mortality by intention-to-treat; and a 60% per protocol reduction in overall CRC mortality, including a 75% mortality reduction from recto-sigmoid cancer. Colonoscopy is currently the most “popular” CRC screening test, despite an absence of data demonstrating its superiority over other tests. Within gastroenterology, much attention is focused on monitoring the performance of colonoscopy through parameters such as the extent of examination (to the cecum and by which landmarks?); withdrawal time spent examining the mucosa; and adenoma detection rate. Evidence for the effectiveness of colonoscopy in reducing CRC incidence and mortality is indirect. Follow-up of the National Polyp Study cohort suggests a 76–90% reduction in CRC incidence when compared to 3 reference populations. (13) Kahi and colleagues compared the observed CRC rate in a cohort of screened persons with a median of 7 years follow-up and found a significant reduction in CRC incidence of 67% (95% CI, 38–90%) when compared with SEER data; CRC mortality was reduced by 65%, though this finding was not statistically significant. (14) The degree and duration of protection of colonoscopy from CRC has been questioned in two recent studies. In a population-based case-control study, Baxter and colleagues found that colonoscopy reduced CRC mortality by 37% overall. Colonoscopy reduced left-sided CRC mortality by 67%, but reduced right-sided mortality by just 1%, a non-significant result. (15) In a population-based retrospective cohort study, Lakoff and colleagues looked at risk of CRC after a “negative” colonoscopy, finding that colonoscopy was protective later and less consistently for the proximal colon than for the distal colon. (16) Both technical and biological factors may explain the apparent and relative ineffectiveness of colonoscopy in the right colon in the Baxter and Lakoff studies, respectively. What's coming? Future studies are expected on how colonoscopy can improve detection of adenomas; on FIT test performance, both qualitative and quantitative; on CT colonography performance and acceptance, the latter of which would be enhanced by use of a “virtual prep”; on test performance and logistics of fecal DNA; and on blood-based biomarkers for CRC/advanced adenomas. Finally, we might also expect tailoring of both screening and surveillance based on improved risk stratification. Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN14-06.

Adenoma detection rate (ADR) is widely used as an index of colonoscopy quality management. Although advanced adenomas can be found less frequently than non-advanced adenomas, advanced adenomas have a higher clinical significance during screening for colorectal cancer. The aim of this study was to investigate the correlation between advanced and non-advanced ADR among colonoscopists. This study is an observational study of a cohort of patients undergoing screening colonoscopy between 2009 and 2010. We collected the data on patients' characteristics and colonoscopic findings. The detection rates of adenoma and advanced adenoma were calculated. Logistic regression was used to determine the effects of variables on advanced adenoma detection, and spearman's rank-order correlation was used to evaluate the relationship between advanced ADR and ADR. A total of 561 patients underwent screening colonoscopy by 18 experienced colonoscopists. Most colonoscopists had adequate (>20%) ADRs. Logistic regression showed that increased patient age (OR 1.07 per 1 year increase, 95% CI 1.009-1.133, p=0.023) and male gender (OR 1.860, 95% CI 0.764-4.529, p=0.171) were associated with advanced ADR. When colonoscopists were divided into two groups on the basis of advanced ADR of 5%, ADR was also significantly higher in the group having higher level of advanced ADR. However, there was no correlation between advanced ADR and ADR among colonoscopists as an individual. Colonoscopists' advanced ADRs were independent of their ADRs, indicating that advanced ADR could be quite low even among colonoscopists with acceptable ADRs. Thus, there seems to be a limitation in using ADR as an adequate index of colonoscopy quality management.

The incidence of colorectal cancer (CRC) in individuals under 50 is increasing worldwide. We conducted an analysis of colonoscopy findings in high-risk individuals under 50 in the CRC screening program in Tianjin, China, to determine the detection rate and risk factors of advanced adenomas (AA), advanced colorectal neoplasia (ACN), colorectal neoplasia (CN). Our study investigated individuals aged 40-49 who underwent CRC screening and completed colonoscopy, 2012-2020, while the 50-54 age group served as a control. We compared the detection rates of AA, ACN, and CN among three age groups using univariate and multivariable logistic regression analyses, and investigated the risk factors associated with AA, ACN, and CN among individuals aged 40-49. We found a gradual increase in the detection rate of AA, ACN, and CN among individuals aged 40-54. The detection rates for AA (OR 0.58; 95% CI 0.41-0.81), ACN (OR 0.58; 95% CI 0.43-0.77), and CN (OR 0.64; 95% CI 0.56-0.74) were lower in individuals aged 40-44 compared to 45-49. The detection rates of AA (OR 1.08; 95% CI 0.87-1.34) and ACN (OR 1.12; 95% CI 0.93-1.35) in individuals aged 45-49 were comparable with 50-54. Besides, lifestyle factors, BMI, and FIT are not associated with the detection rates of AA, ACN, and CN among individuals aged 40-49. Our study reveals screening data in individuals under 50, indicating comparable detection rates of AA and ACN in individuals aged 45-49 and 50-54. These findings provide valuable data support for optimizing the optimal age to initiate screening.

Uptake of Colorectal Cancer Screening in 45 to 49 Year Olds: An Early-Inning View from the Endoscopy Suite

COVID-19: An Opportunity to Reimagine Colorectal Cancer Diagnostic Testing—A New Paradigm Shift

Background:Colorectal cancer (CRC) screening is effective in reducing CRC incidence and mortality. The aim of this study was to retrospectively determine and compare the detection rate of adenomas, advanced adenomas (AAs) and CRCs, and the number needed to screen (NNS) of individuals in an average-risk Chinese population of different ages and genders.Methods:This was a retrospective study performed at the Institute of Health Management, Chinese People's Liberation Army General Hospital. Colonoscopy results were analyzed for 53,152 individuals finally enrolled from January 2013 to December 2019. The detection rate of adenomas, AAs, or CRCs was computed and the characteristics between men and women were compared using chi-squared test.Results:The average age was 48.8 years (standard deviation [SD], 8.5 years) for men and 50.0 years (SD, 9.0 years) for women, and the gender rate was 66.27% (35,226) vs. 33.73% (17,926). The detection rates of adenomas, AAs, serrated adenomas, and CRCs were 14.58% (7750), 3.09% (1641), 1.23% (653), and 0.59% (313), respectively. Men were statistically significantly associated with higher detection rates than women in adenomas (17.20% [6058/35,226], 95% confidence interval [CI] 16.74–17.53% vs. 9.44% [1692/17,926], 95% CI 8.94–9.79%, P < 0.001), AAs (3.72% [1309], 95% CI 3.47–3.87% vs. 1.85% [332], 95% CI 1.61–2.00%, P < 0.001), and serrated adenomas (1.56% [548], 95% CI 1.43–1.69% vs. 0.59% [105], 95% CI 0.47–0.70%, P < 0.001). The detection rate of AAs in individuals aged 45 to 49 years was 3.17% (270/8510, 95% CI 2.80–3.55%) in men and 1.69% (69/4091, 95% CI 1.12–1.86%) in women, and their NNS was 31.55 (95% CI 28.17–35.71) in men and 67.11 (95% CI 53.76–89.29) in women. The NNS for AAs in men aged 45 to 49 years was close to that in women aged 65 to 69 years (29.07 [95% CI 21.05–46.73]).Conclusions:The detection rates of adenomas, AAs, and serrated adenomas are high in the asymptomatic population undergoing a physical examination and are associated with gender and age. Our findings will provide important references for effective population-based CRC screening strategies in the future.

ObjectivesQuantitative faecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening in the Western countries, whereas qualitative FITs are preferred in China. The present study aimed to compare...

Fecal immunochemical tests (FITs) and flexible sigmoidoscopies are commonly used modalities for colorectal cancer (CRC) screening. We performed a systematic review and meta-analysis to compare the effectiveness of FIT and sigmoidoscopy in CRC screening. PRISMA statement and Cochrane guidelines were followed for this review. Digital dissertation databases were searched from inception till December 1st 2020 and randomized clinical trials comparing the detection rates of CRC for FIT and sigmoidoscopy were included. Outcomes for analysis included participation rates and detection rates of CRC, advanced adenomas and advanced colorectal neoplasia for both screening modalities. Five randomized clinical trials with a total of 261,755 patients were included for the analysis. The participation rate for FIT was significantly higher compared to flexible sigmoidoscopy (OR 2.11, 95% CI 1.29-3.44, p=0.003). In intention-to-screen analysis, the detection rate for advanced colorectal neoplasia was significantly lower with FIT (OR 0.62, 95% CI 0.45-0.84, p=0.002) as compared to flexible sigmoidoscopy but not statistically different for CRC (OR 1.15, 95% CI 0.65-2.02, p=0.63). Despite lower participation amongst patients, CRC screening with flexible sigmoidoscopy leads to higher detection of advanced colorectal neoplasia, when compared to a single round of fecal immunochemical testing.

Colorectal cancer (CRC) screening reduces disease burden, but the comparative performance of various screening strategies remains unclear. We evaluated the performance of four screening strategies based on questionnaire-based risk assessment (QRA) and fecal immunochemical test (FIT), followed by colonoscopy. In this population-based study, 14,327 residents aged 40-74 years from 13 regions in Shandong Province, China, were invited to undergo QRA, FIT, and colonoscopy between January 2024 and December 2025. Based on test results, we constructed four strategies: QRA-only, FIT-only, parallel (QRA or FIT positive), and tandem (QRA and FIT positive) combinations. The detection rate of CRC and advanced adenoma (AA), number needed to scope (NNS), and cost per case detected were compared. In total, 4982, 1806, 5970, and 764 individuals were identified as high-risk for each strategy. The tandem strategy detected 33 CRCs (4.32%) and 199 AAs (26.03%), compared with 35 (0.71%) and 553 (11.22%) in the QRA-only strategy, 68 (3.77%) and 340 (18.86%) in the FIT-only strategy, and 70 (1.17%) and 694 (11.62%) in the parallel strategy. Across subgroups defined by older age, male, and early-stage disease, the tandem strategy consistently yielded higher detection rates. The NNS to detect one CRC was 141, 27, 86, and 24, and the corresponding costs per CRC detected were $9874.31, $2097.88, $7084.68, and $1700.71 for each strategy. The tandem strategy combining QRA and FIT demonstrated superior performance in CRC screening. In resource-constrained settings, tandem strategies that jointly integrate risk assessment and FIT may improve the allocation and utilization of screening resources.