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.

Multilevel and multicomponent intervention to promote colorectal cancer screening among underserved Vietnamese Americans: A cluster randomized trial.

Purpose: The fecal immunochemical test (FIT) is a non-invasive method for colorectal cancer (CRC) screening, particularly effective in underserved Vietnamese American communities with low screening rates. This study reports on a culturally tailored multilevel intervention, incorporating FIT, aimed at increasing CRC screening among these populations aged 50 or above in the Greater Philadelphia metropolitan area. Methods: From 2017 to 2020, we conducted a two-arm cluster randomized controlled trial to test the efficacy of a culturally tailored, multicomponent multilevel intervention aimed at increasing CRC screening uptake via enhanced self-awareness and self-efficacy, improved access to care, and changes in social norms and removal of stigma. The intervention group received multicomponent, multilevel CRC intervention including provision of a FIT self-sampling kit, with intervention approaches informed by the Centers for Disease Control's Clinical Preventive Services (CPS) Guidelines for adults 50+. The control group received only the CPS education. Results: The study sample consisted of 746 eligible Vietnamese American participants recruited from 20 community-based organizations, with 95% having limited English proficiency. At 12-month follow-up, the intervention group showed substantially higher rates of FIT completion (89.56% vs. 7.59%, p < .001) and any CRC testing (91.48% vs. 42.41%, p < .001) compared to the control group. Conclusion: The results suggest that the community-based, culturally-tailored multilevel intervention, which incorporates with FIT self-testing, effectively enhances CRC screening among low-income Vietnamese Americans. Additionally, these results underscore the significance of community-oriented strategies, like collaborating with relevant community-based organizations, in achieving CRC screening targets.

Effective strategies for Fecal Immunochemical Tests (FIT) programs to improve colorectal cancer screening uptake among populations with limited access to the healthcare system: a rapid review.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer death globally. CRC screening can reduce the incidence and mortality of CRC. However, socially disadvantaged groups may disproportionately benefit less from screening programs due to their limited access to healthcare. This poor access to healthcare services is further aggravated by intersecting, cumulative social factors associated with their sociocultural background and living conditions. This rapid review systematically reviewed and synthesized evidence on the effectiveness of Fecal Immunochemical Test (FIT) programs in increasing CRC screening in populations who do not have a regular healthcare provider or who have limited healthcare system access. METHODS: We used three databases: Ovid MEDLINE, Embase, and EBSCOhost CINAHL. We searched for systematic reviews, meta-analysis, and quantitative and mixed-methods studies focusing on effectiveness of FIT programs (request or receipt of FIT kit, completion rates of FIT screening, and participation rates in follow-up colonoscopy after FIT positive results). For evidence synthesis, deductive and inductive thematic analysis was conducted. The findings were also classified using the Cochrane Methods Equity PROGRESS-PLUS framework. The quality of the included studies was assessed. RESULTS: Findings from the 25 included primary studies were organized into three intervention design-focused themes. Delivery of culturally-tailored programs (e.g., use of language and interpretive services) were effective in increasing CRC screening. Regarding the method of delivery for FIT, specific strategies combined with mail-out programs (e.g., motivational screening letter) or in-person delivery (e.g., demonstration of FIT specimen collection procedure) enhanced the success of FIT programs. The follow-up reminder theme (e.g., spaced out and live reminders) were generally effective. Additionally, we found evidence of the social determinants of health affecting FIT uptake (e.g., place of residence, race/ethnicity/culture/language, gender and/or sex). CONCLUSIONS: Findings from this rapid review suggest multicomponent interventions combined with tailored strategies addressing the diverse, unique needs and priorities of the population with no regular healthcare provider or limited access to the healthcare system may be more effective in increasing FIT screening. Decision-makers and practitioners should consider equity and social factors when developing resources and coordinating efforts in the delivery and implementation of FIT screening strategies.

Profiling small RNAs in fecal immunochemical tests: is it possible?

Fecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers. Colorectal cancer (CRC) screening based on the fecal immunochemical test (FIT) is an effective tool for prevention of cancer development. However, due to the poor sensitivity of FIT especially for premalignant lesions, there is a need for implementation of complementary tests. Improving the identification of individuals who would benefit from further investigation with colonoscopy using molecular analysis, such as miRNA profiling of FIT samples, would be ideal due to their widespread use. In the present study, we assessed the feasibility of applying small RNA sequencing to measure human miRNAs in FIT leftover buffer in samples from two European screening populations. We showed robust detection of miRNAs with profiles similar to those obtained from specimens sampled using the established protocol of RNA stabilizing buffers, or in long-term archived samples. Detected miRNAs exhibited differential abundances for CRC, advanced adenoma, and control samples that were consistent for FIT and RNA-stabilizing buffers. Interestingly, the sequencing data also allowed for concomitant evaluation of small RNA-based microbial profiles. We demonstrated that it is possible to explore the human miRNome in FIT leftover samples across populations and envision that the analysis of small RNA biomarkers can complement the FIT in large scale screening settings.

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.

Increasing the accuracy of colorectal cancer screening.

INTRODUCTION: Colorectal cancer (CRC) is a major health issue, being responsible for nearly 10% of all cancer-related deaths. Since CRC is often an asymptomatic or paucisymptomatic disease until it reaches advanced stages, screening is crucial for the diagnosis of preneoplastic lesions or early CRC. AREAS COVERED: The aim of this review is to summarize the literature evidence on currently available CRC screening tools, with their pros and cons, focusing on the level of accuracy reached by each test over time. We also provide an overview of novel technologies and scientific advances that are currently being investigated and that in the future may represent real game-changers in the field of CRC screening. EXPERT OPINION: We suggest that best screening modalities are annual or biennial FIT and colonoscopy every 10 years. We believe that the introduction of artificial intelligence (AI)-tools in the CRC screening field could lead to a significant improvement of the screening efficacy in reducing CRC incidence and mortality in the future. More resources should be put into implementing CRC programs and support research project to further increase the accuracy of CRC screening tests and strategies.

Yield of Post-Acute Diverticulitis Colonoscopy for Ruling Out Colorectal Cancer.

Background and Aims: Colonoscopy is recommended post-acute diverticulitis (AD) to exclude underlying adenocarcinoma (CRC). However, post-AD colonoscopy utility remains controversial. We aimed to examine yield of post-AD colonoscopy in our majority-Hispanic patient population. Methods: Patients undergoing post-AD colonoscopy between 11/1/2015-7/31/2021 were identified from a prospectively maintained endoscopic database. AD cases without computed tomography confirmation were excluded. Pertinent data, including complicated vs uncomplicated AD, fecal immunochemical test (FIT) result post-AD/pre-colonoscopy, and number/type/location of non-advanced adenomas, advanced adenomas, and CRC, were abstracted. Analyses were conducted using two-sample Wilcoxon rank-sum and Fisher's exact tests. Results: 208 patients were included, of whom 62.0% had uncomplicated AD. Median age was 53, 54.3% were female, and 77.4% were Hispanic. Ninety non-advanced adenomas were detected in 45 patients (21.6%), in addition to advanced adenoma in eight patients (3.8%). Two patients (1.0%) had CRC, both of whom had complicated AD in the same location seen on imaging, and one of whom was FIT+ (the other had not undergone FIT). Patients with uncomplicated versus complicated AD had similarly low rates of advanced adenomas (4.7% vs. 2.5%, p=0.713). FIT data were available in 51 patients and positive in three (5.9%); non-advanced adenomas were found in all three FIT+ patients. No FIT- patient had an advanced adenoma or CRC. Conclusion: Colonoscopy post-AD is generally low yield, with CRC being rare and found only in those with complicated AD. Colonoscopy post-complicated AD appears advisable, whereas less invasive testing (e.g. FIT) may be considered post-uncomplicated AD to inform the need for colonoscopy.

Mailed fecal testing and patient navigation versus usual care to improve rates of colorectal cancer screening and follow-up colonoscopy in rural Medicaid enrollees: a cluster-randomized controlled trial.

BACKGROUND: Screening reduces incidence and mortality from colorectal cancer (CRC), yet US screening rates are low, particularly among Medicaid enrollees in rural communities. We describe a two-phase project, SMARTER CRC, designed to achieve the National Cancer Institute Cancer MoonshotSM objectives by reducing the burden of CRC on the US population. Specifically, SMARTER CRC aims to test the implementation, effectiveness, and maintenance of a mailed fecal test and patient navigation program to improve rates of CRC screening, follow-up colonoscopy, and referral to care in clinics serving rural Medicaid enrollees. METHODS: Phase I activities in SMARTER CRC include a two-arm cluster-randomized controlled trial of a mailed fecal test and patient navigation program involving three Medicaid health plans and 30 rural primary care practices in Oregon and Idaho; the implementation of the program is supported by training and practice facilitation. Participating clinic units were randomized 1:1 into the intervention or usual care. The intervention combines (1) mailed fecal testing outreach supported by clinics, health plans, and vendors and (2) patient navigation for colonoscopy following an abnormal fecal test result. We will evaluate the effectiveness, implementation, and maintenance of the intervention and track adaptations to the intervention and to implementation strategies, using quantitative and qualitative methods. Our primary effectiveness outcome is receipt of any CRC screening within 6 months of enrollee identification. Our primary implementation outcome is health plan- and clinic-level rates of program delivery, by component (mailed FIT and patient navigation). Trial results will inform phase II activities to scale up the program through partnerships with health plans, primary care clinics, and regional and national organizations that serve rural primary care clinics; scale-up will include webinars, train-the-trainer workshops, and collaborative learning activities. DISCUSSION: This study will test the implementation, effectiveness, and scale-up of a multi-component mailed fecal testing and patient navigation program to improve CRC screening rates in rural Medicaid enrollees. Our findings may inform approaches for adapting and scaling evidence-based approaches to promote CRC screening participation in underserved populations and settings. TRIAL REGISTRATION: Registered at clinicaltrial.gov ( NCT04890054 ) and at the NCI's Clinical Trials Reporting Program (CTRP #: NCI-2021-01032) on May 11, 2021.

Factors Associated With Advanced Colorectal Neoplasia in Patients With CKD.

RATIONALE & OBJECTIVE: The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients with CKD stages 3-5, including those treated with maintenance dialysis or transplantation across 11 sites in Australia, New Zealand, Canada, and Spain, were screened for colorectal neoplasia using a fecal immunochemical test (FIT) as part of the Detecting Bowel Cancer in CKD (DETECT) Study. EXPOSURE: Baseline characteristics for patients at the time of study enrollment were ascertained, including duration of CKD, comorbidities, and medications. OUTCOME: Advanced colorectal neoplasia was identified through a 2-step verification process with colonoscopy following positive FIT and 2-year clinical follow-up for all patients. ANALYTICAL APPROACH: Potential factors associated with advanced colorectal neoplasia were explored using multivariable logistic regression. Sensitivity analyses were performed using grouped LASSO (least absolute shrinkage and selection operator) logistic regression. RESULTS: Among 1,706 patients who received FIT-based screening-791 with CKD stages 3-5 not receiving kidney replacement therapy (KRT), 418 receiving dialysis, and 497 patients with a functioning kidney transplant-117 patients (6.9%) were detected to have advanced colorectal neoplasia (54 with CKD stages 3-5 without KRT, 34 receiving dialysis, and 29 transplant recipients), including 9 colorectal cancers. The factors found to be associated with advanced colorectal neoplasia included older age (OR per year older, 1.05 [95% CI, 1.03-1.07], P<0.001), male sex (OR, 2.27 [95% CI, 1.45-3.54], P<0.001), azathioprine use (OR, 2.99 [95% CI, 1.40-6.37], P=0.005), and erythropoiesis-stimulating agent use (OR, 1.92 [95% CI, 1.22-3.03], P=0.005). Grouped LASSO logistic regression revealed similar associations between these factors and advanced colorectal neoplasia. LIMITATIONS: Unmeasured confounding factors. CONCLUSIONS: Older age, male sex, erythropoiesis-stimulating agents, and azathioprine were found to be significantly associated with advanced colorectal neoplasia in patients with CKD.

Age, male sex, smoking and metabolic syndrome as risk factors of advanced colorectal neoplasia for fecal immunochemical test negative patients.

BACKGROUND: Fecal immunochemical test (FIT) is worldwide strategy for colorectal cancer screening. The subjects with negative FIT still have the risk of an advanced colorectal neoplasia (AN), including adenoma with villous histology, high grade dysplasia or larger than 1 cm in size, or adenocarcinoma. The study determined the risk factors associated with AN in FIT-negative subjects. METHODS: The study included asymptomatic subjects who received health checkup colonoscopy and have provided FIT study within 6 months prior to colonoscopy. The risk factors to have AN in cases with negative FIT were analyzed. The numbers of colonoscopies needed to detect one AN were calculated for the subjects with different risk factors. RESULTS: There were 1411 cases, 85 with positive FIT and 1326 with negative FIT within 6 months before colonoscopy. In FIT positive and FIT negative cases, 45.9% and 34.6% were found to have colorectal adenoma, while 20.2% and 4.6% had AN, respectively. The univariate and multivariate logistic regression analyses showed that age more than 50 years old, male sex, smoking history and metabolic syndrome were the significant risk factors to have AN in the FIT negative cases. For cases with negative FIT to have these risk factors, the number of colonoscopies needed to detect one AN was 3.7, lower than 4.5 of the cases with positive FIT. CONCLUSION: For the cases with negative FIT, colonoscopy screening should be considered for those male patients over 50 years old, with a history of smoking and metabolic syndrome to detect AN.

Colorectal Cancer screening in ambulatory healthcare service clinics in Abu Dhabi, United Arab Emirates in 2015-2016.

BACKGROUND: Colorectal cancer (CRC) is a major public health issue due to high morbidity and mortality. Different screening programs were implemented to reduce its burden. OBJECTIVES: To estimate the prevalence of CRC screening uptake using fecal immunochemical test (FIT) or guaiac fecal occult blood testing (gFOBT) in Emirati nationals. Other objectives were to measure the incidence of CRC in the screened population, to measure the outcomes of follow-up screening colonoscopy after positive FIT/gFOBT and to identify the causes of not performing follow-up screening colonoscopy after positive FIT/gFOBT. METHODOLOGY: Adult Emirati nationals aged 40-75 years who visited Ambulatory healthcare services clinics, Abu Dhabi in 2015-2016 were included in the study. The electronic medical records of the eligible individuals were reviewed retrospectively. The prevalence of CRC screening was measured among the eligible population using the FIT/gFOBT. The IBM SPSS Statistics program, version 21.0.0, was used for analysis. RESULT: 45,147 unique individuals were eligible for screening, and only 23.5% were screened using FIT/gFOBT. Of the screened individuals, 13.5% had positive FIT/ gFOBT, and 30.5% of those underwent follow-up screening colonoscopy. CRC was diagnosed in 11 individuals. Colonic polyp were found in 30.5% of individuals who had undergone a follow-up colonoscopy. Collectively 933 individuals did not undergo follow-up screening colonoscopy after having a positive FIT/gFOBT, and about 36.3% had collected the result and referred to a gastroenterologist but did not attend the appointment. CONCLUSION: CRC screening uptake using FIT/gFOBT is low among the adult Emirati nationals.

The Roadmap of Colorectal Cancer Screening.

Colorectal cancer (CRC) is the third most common form of cancer in terms of incidence and the second in terms of mortality worldwide. CRC develops over several years, thus highlighting the importance of early diagnosis. National screening programs based on fecal occult blood tests and subsequent colonoscopy have reduced the incidence and mortality, however improvements are needed since the participation rate remains low and the tests present a high number of false positive results. This review provides an overview of the CRC screening globally and the state of the art in approaches aimed at improving accuracy and participation in CRC screening, also considering the need for gender and age differentiation. New fecal tests and biomarkers such as DNA methylation, mutation or integrity, proteins and microRNAs are explored, including recent investigations into fecal microbiota. Liquid biopsy approaches, involving novel biomarkers and panels, such as circulating mRNA, micro- and long-non-coding RNA, DNA, proteins and extracellular vesicles are discussed. The approaches reported are based on quantitative PCR methods that could be easily applied to routine screening, or arrays and sequencing assays that should be better exploited to describe and identify candidate biomarkers in blood samples.

To do or not to do - a survey study on factors associated with participating in the Danish screening program for colorectal cancer.

BACKGROUND: Screening programs for colorectal cancer (CRC) exist in many countries, and with varying participation rates. The present study aimed at identifying socio-demographic factors for accepting a cost-free screening offer for CRC in Denmark, and to study if more people would accept the screening offer if the present fecal test was replaced by a blood test. METHODS: We used a cross-sectional survey design based on a representative group of 6807 Danish citizens aged 50-80 years returning a fully answered web-based questionnaire with socio-demographic data added from national registries. Data were analyzed in STATA and based on bivariate analyses followed by regression models. RESULTS: Danes in general have a high level of lifetime participation (+ 80%) in the national CRC screening program. The results of the stepwise logistic regression model to predict CRC screening participation demonstrated that female gender, higher age, higher income, and moderate alcohol intake were positively associated with screening participation, whereas a negative association was observed for higher educational attainment, obesity, being a smoker, and higher willingness to take health risks. Of the 1026 respondents not accepting the screening offer, 61% were willing to reconsider their initial negative response if the fecal sampling procedure were replaced by blood sampling. CONCLUSION: The CRC screening program intends to include the entire population within a certain at-risk age group. However, individual factors (e.g. sex, age obesity, smoking, risk aversity) appear to significantly affect willingness to participate in the screening program. From a preventive perspective, our findings indicate the need for a more targeted approach trying to reach these groups.

A New Biomarker of Fecal Bacteria for Non-Invasive Diagnosis of Colorectal Cancer.

Background: The intestinal flora is correlated with the occurrence of colorectal cancer. We evaluate a new predictive model for the non-invasive diagnosis of colorectal cancer based on intestinal flora to verify the clinical application prospects of the intestinal flora as a new biomarker in non-invasive screening of colorectal cancer. Methods: Subjects from two independent Asian cohorts (cohort I, consisting of 206 colorectal cancer and 112 healthy subjects; cohort II, consisting of 67 colorectal cancer and 54 healthy subjects) were included. A probe-based duplex quantitative PCR (qPCR) determination was established for the quantitative determination of candidate bacterial markers. Results: We screened through the gutMEGA database to identify potential non-invasive biomarkers for colorectal cancer, including Prevotella copri (Pc), Gemella morbillorum (Gm), Parvimonas micra (Pm), Cetobacterium somerae (Cs), and Pasteurella stomatis (Ps). A predictive model with good sensitivity and specificity was established as a new diagnostic tool for colorectal cancer. Under the best cutoff value that maximizes the sum of sensitivity and specificity, Gm and Pm had better specificity and sensitivity than other target bacteria. The combined detection model of five kinds of bacteria showed better diagnostic ability than Gm or Pm alone (AUC = 0.861, P < 0.001). These findings were further confirmed in the independent cohort II. Particularly, the combination of bacterial markers and fecal immunochemical test (FIT) improved the diagnostic ability of the five bacteria (sensitivity 67.96%, specificity 89.29%) for patients with colorectal cancer. Conclusion: Fecal-based colorectal cancer-related bacteria can be used as new non-invasive diagnostic biomarkers of colorectal cancer. Simultaneously, the molecular biomarkers in fecal samples are similar to FIT, have the applicability in combination with other detection methods, which is expected to improve the sensitivity of diagnosis for colorectal cancer, and have a promising prospect of clinical application.

Fecal microbial DNA markers serve for screening colorectal neoplasm in asymptomatic subjects.

BACKGROUND AND AIM: We have previously shown that fecal microbial markers might be useful for non-invasive diagnosis of colorectal cancer (CRC) and adenoma. Here, we assessed the application of microbial DNA markers, as compared with and in combination with fecal immunochemical test (FIT), in detecting CRC and adenoma in symptomatic patients and asymptomatic subjects. METHODS: We recruited 676 subjects [210 CRC, 115 advanced adenoma (AA), 86 non-advanced adenoma, and 265 non-neoplastic controls], including 241 symptomatic and 435 asymptomatic subjects. Fecal abundances of Fusobacterium nucleatum, a Lachnoclostridium sp. m3, Bacteroides clarus, and Clostridium hathewayi were quantified by quantitative PCR. Combining score of the four microbial markers (4Bac) and diagnostic prediction were determined using our previously established scoring model and cutoff values and FIT with a cutoff of 100 ng Hb/mL. RESULTS: 4Bac detected similar percentages of CRC [85.3% (95%CI: 79.2-90.2%) vs 84.9% (68.1-94.9%)] and AA [35.7% (12.8-64.9%) vs 38.6% (29.1-48.8%)], while FIT detected more CRC [72.1% (63.7-79.4%) vs 66.7% (48.2-82.0%)] and AA [28.6% (8.4-58.1%) vs 16.8% (10.1-25.6%)], in symptomatic vs asymptomatic subjects, respectively. Focusing on the asymptomatic cohort, 4Bac was more sensitive for diagnosing CRC and AA than FIT (P < 0.001), with lower specificity [83.3% (77.6-88.0%) vs 98.6% (96.0-99.7%)]. FIT failed to detect any non-advanced adenoma [0% (0.0-4.2%)] compared with 4Bac [41.9% (31.3-53.0%), P < 0.0001]. Combining 4Bac with FIT improved sensitivities for CRC [90.9% (75.7-98.1%)] and AA [48.5% (38.4-58.7%)] detection. CONCLUSION: Quantitation of fecal microbial DNA markers may serve as a new test, stand alone, or in combination with FIT for screening colorectal neoplasm in asymptomatic subjects.

Health plan adaptations to a mailed outreach program for colorectal cancer screening among Medicaid and Medicare enrollees: the BeneFIT study.

BACKGROUND: Promoting uptake of evidence-based innovations in healthcare systems requires attention to how innovations are adapted to enhance their fit with a given setting. Little is known about real-world variation in how programs are delivered over time and across multiple populations and contexts, and what motivates adaptations. METHODS: As part of the BeneFIT study of mailed fecal immunochemical tests (FIT) to increase colorectal cancer screening, we interviewed 9 leaders from two participating Medicaid/Medicare health insurance plans to examine adaptations to their health plan-initiated mailed FIT outreach programs in the second year of implementation. We applied an adaptation and modification model developed by Stirman and colleagues to document content and context modifications made to the two programs. RESULTS: Both health plans made substantial changes to their programs in the second year; adaptations differed substantially across health plans. In Health Plan Oregon, adaptations generally targeted health centers and member populations, most content adaptations involved tailoring program components, and the program was expanded to four additional health centers. In contrast, Health Plan Washington's second-year content adaptations were primarily at the level of members, and generally involved adding program components. Moreover, Health Plan Washington undertook large-scale context adaptations to the setting where the program was led (local vs. national), the personnel who administered the program (vendor and staffing), and the population selected for outreach (limiting outreach to dual-eligible members). CONCLUSIONS: Both programs implemented a variety of adaptations that reflected the values and incentives of the broader health plan contexts. Financial incentives for screening allowed Health Plan Oregon to expand but led Health Plan Washington to offer more targeted outreach to a subset of eligible enrollees. The breadth of changes made by each health system reflects the necessity of evaluating programs in context and adjusting to specific challenges as they are identified. Further research is needed to understand the effects of these types of adaptations on program efficiency and enrollee and health system outcomes.

Mailed fecal immunochemical test outreach for colorectal cancer screening: Summary of a Centers for Disease Control and Prevention-sponsored Summit.

Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented.

Effect of Various Invitation Schemes on the Use of Fecal Immunochemical Tests for Colorectal Cancer Screening: Protocol for a Randomized Controlled Trial.

BACKGROUND: Fecal occult blood testing has been offered for many years in the German health care system, but participation rates have been notoriously low. OBJECTIVE: The aim of this study is to evaluate the effect of various personal invitation schemes on the use of fecal immunochemical tests (FITs) in persons aged 50-54 years. METHODS: This study consists of a three-armed randomized controlled trial: (1) arm A: an invitation letter from a health insurance plan including a FIT test kit, (2) arm B: an invitation letter from a health insurance plan including an offer to receive a free FIT test kit by mail upon easy-to-handle request (ie, by internet, fax, or reply mail), and (3) arm C: an information letter on an existing colonoscopy offer (ie, control). Within arms A and B, a random selection of 50% of the study population will receive reminder letters, the effects of which are to be evaluated in a substudy. RESULTS: A total of 17,532 persons aged 50-54 years in a statutory health insurance plan in the southwest of Germany-AOK Baden-Wuerttemberg-were sent an initial invitation, and 5825 reminder letters were sent out. The primary end point is FIT usage within 1 year from receipt of invitation or information letter. The main secondary end points include gender-specific FIT usage within 1 year, rates of positive test results, rates of colonoscopies following a positive test result, and detection rates of advanced neoplasms. The study was launched in September 2017. Data collection and workup were completed in fall 2019. CONCLUSIONS: This randomized controlled trial will provide important empirical evidence for enhancing colorectal cancer screening offers in the German health care system. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00011858; https://bit.ly/2UBTIdt. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16413.

Older age, symptoms, or anemia: Which factors increase colorectal cancer risk with a positive fecal immunochemical test?

BACKGROUND AND AIM: Fecal immunochemical tests (FIT) are used to screen asymptomatic individuals aged 50-74 years for colorectal cancer (CRC) within the Australian screening program. Gastrointestinal symptoms or iron deficiency anemia (IDA) may also drive primary care physicians to request a FIT. This study aimed to examine factors that may increase neoplasia risk associated with a positive FIT, specifically age, gastrointestinal symptoms, or IDA. METHODS: A retrospective audit was performed on colonoscopies performed in a single hospital in South Australia for a positive FIT (from all referral sources) between 2014 and 2017. Patients aged < 50 years, or who had a colonoscopy in the preceding 5 years, were excluded. A subgroup (n = 198) was evaluated to assess whether age ≥ 75 years, symptoms, or IDA, as well as other demographics, comorbidities, and medications, were associated with risk of neoplasia. Features found to be associated with risk for CRC or high-risk adenoma were examined in the entire cohort using multivariate analysis. RESULTS: Colonoscopies (750/4221, 17.8%) were completed in patients ≥ 50 years for a positive FIT. Of these, 7.6% (n = 57) also had gastrointestinal symptoms, 5.5% (n = 41) IDA, and 13.1% (n = 98) were ≥ 75 years. At colonoscopy, 2.8% (n = 21) were diagnosed with CRC and 23.2% (n = 174) with high-risk adenoma. CRC was more prevalent in ≥ 75 years compared with 50-74 years (7.1% vs 2.1%, P = 0.005), and associated with symptoms (15.8% vs 1.7%, P < 0.001), and IDA (14.6% vs 2.1%, P < 0.001). Multivariate analysis showed that IDA (odds ratio 7.68, P < 0.001) and symptoms (odds ratio 10.37, P < 0.001), but not age, were independent risk factors for CRC. CONCLUSION: The presence of gastrointestinal symptoms or IDA, independent of age, is associated with an increased risk for CRC following a positive FIT.

Physician-office vs home uptake of colorectal cancer screening using FOBT/FIT among screening-eligible US adults.

BACKGROUND: Guidelines of the American Cancer Society and US Preventive Services Task Force specify that colorectal cancer (CRC) screening using guaiac-based fecal occult blood test (FOBT)/fecal immunochemical test (FIT) should be done at home. We therefore examined the prevalence and correlates of CRC screening using FOBT/FIT in physicians' office vs at home. METHODS: Analysis of 9493 respondents 50-75 years old from the Cancer Control Supplement of the 2015 National Health Interview Survey was conducted. Weighted multivariable logistic regression was used to identify the determinants of in-office vs home use of FOBT/FIT for CRC screening. RESULTS: Of the overall sample of screening-eligible adults (n = 9403), only 937 (10.4%) respondents underwent CRC screening using FOBT/FIT within the past year; among this screening population, 279 (28.3%) respondents were screened in-office. We found that sociodemographic factors alone, not CRC risk factors, determined whether FOBT/FIT would be used in-office or at home. Hispanics had greater odds of being screened in-office using FOBT/FIT (aOR: 2.04; 95% CI: 1.05-3.99). Compared with those 50-59 years old, respondents 70-75 years old were less likely to be screened in-office using FOBT/FIT (aOR: 0.44, 95% CI: 0.25-0.79). Similarly, individuals residing in the Western region of the country had lower odds of in-office FOBT/FIT (aOR: 0.26; 95% CI: 0.11-0.58). CONCLUSION: Amid low overall uptake rates of FOBT/FIT in the United States, in-physician office testing is high, indicative of a missed opportunity for effective screening and poor adherence of physicians to national guidelines. Sociodemographic factors are determinants of uptake of FOBT/FIT at home or in-office and should be considered in designing interventions aimed at providers and the general population.