New stool tests for colorectal cancer screening: a systematic review focusing on performance characteristics and practicalness

New stool tests may be promising tools for future colorectal cancer (CRC) screening. The aim of this review was to summarize current evidence of performance characteristics and practicalness in a population-based screening setting of recently developed stool tests. The MEDLINE database was searched for relevant articles published until July 2004. Studies were included if they comprised more than 10 cases and more than 10 controls. Details on study population, performance characteristics and stool collection procedure were taken into account. Overall, 29 studies, mostly retrospective, were included, investigating 17 different stool markers or marker combinations. Underlying study populations were very heterogeneous and mostly very small. Half of the studies reported sensitivity for adenomas in addition to sensitivity for CRC, and fewer than half reported sensitivity by tumor stage or location. Performance characteristics of stool tests varied to a large extent. For most DNA-based markers, specificity was about 95% or higher, but sensitivity was mostly low even for invasive CRC. More studies with larger sample sizes were done for protein-based markers, which typically had lower specificity. In most studies, stool samples were frozen within a rather short time period after defecation. While promising performance characteristics have been reported for some tests, more pervasive evidence from larger, prospectively designed studies, which also consider aspects of practicalness, e.g., the possibility of mailing the samples, is needed.     

Blood autoantibodies against tumor-associated antigens as biomarkers in early detection of colorectal cancer

Multiple studies have shown that cancer patients produce detectable autoantibodies against certain tumor-associated antigens, which might be promising blood biomarkers for early detection of colorectal cancer (CRC). We aimed to provide an overview of published studies on blood autoantibody markers for early detection of CRC and to summarize their diagnostic performance. A systematic literature search was performed in PubMed, ISI Web of Knowledge and EMBASE to find relevant studies published until 23 July 2013. Relevant information, such as study population characteristics, autoantibodies studied, analytical methods and diagnostic performance characteristics was independently extracted by two reviewers. Overall, 67 studies evaluating 109 autoantibody markers were included. Most individual markers showed low sensitivity (below 25%) for detecting CRC, along with high specificity close to 100%. Occasionally reported higher sensitivities for specific antibodies are yet to be replicated in independent studies. Generally, more promising results were seen for combinations of multiple autoantibody markers. But again, these promising results are yet to be replicated in other samples. In conclusion, autoantibody signatures may become a promising approach to noninvasive CRC screening. Optimized marker panels are yet to be developed, and promising results require validation in large screening populations.     

Primary care provider perceptions of barriers to and facilitators of colorectal cancer screening in a managed care setting

BACKGROUND: Colorectal cancer (CRC) screening tests (e.g., fecal occult blood testing [FOBT], flexible sigmoidoscopy [FS], etc.) are underused. Primary care providers (PCPs) play a critical role in screening, but barriers to and facilitators of screening as perceived by PCPs in managed care settings are poorly understood. The objectives of the current study were to describe current CRC screening practices and to explore determinants of test use by PCPs in a managed care setting. METHODS: In 2000, a self-administered survey was mailed to a stratified, random sample of 1340 PCPs in a large, network model health maintenance organization in California. RESULTS: The survey response rate was 67%. PCPs indicated that 79% of their standard-risk patients were screened for CRC. PCP-reported median rates of recommendation for the use of specific screening tests were 90% for FOBT and 70% for FS. In logistic regression models, perceived barriers to the use of FOBT and FS included patient characteristics (e.g., education) and PCP-related barriers (e.g., failure to recall that patients were due for testing). Perceived facilitators of the use of FOBT and FS included interventions targeting certain aspects of the health care system (e.g., reimbursement) and interventions targeting certain aspects of the tests themselves (e.g., provision of evidence of a test's effectiveness). Assignment of high priority to screening, integrated medical group (as opposed to independent practice association) affiliation, and the proportion of patients receiving routine health maintenance examinations were positively associated with reported test use. CONCLUSIONS: CRC screening tests appear to be underused in the managed care setting examined in the current study. The perceived barriers and facilitators that were identified can be used to guide interventions aimed at increasing recommendations for, as well as actual performance of, CRC screening.     

Stool- and Blood-Based Molecular Tests in Screening for Colorectal Cancer: Ready for Prime Time?

Purpose of Review

This article serves as a critical review and summary of the role of stool- and blood-based molecular tests for colorectal cancer (CRC) screening indexed in PubMed between 2011 and early 2017. In particular, we focus on assays approved for clinical use and recent findings on novel biomarkers. The biological rationale, clinical performance characteristics, and limitations of these tools are discussed.

Recent Findings

Novel miRNA markers and bacterial DNA markers have been reported and evaluated in case-controlled studies. The plasma-based SEPT9 test and the multi-target stool DNA test (mt-sDNA) have received approval for CRC screening and are available to patients. Mt-sDNA has demonstrated a high accuracy rate in detecting colorectal neoplasia.

Summary

Despite the proven benefits of CRC screening, a large percentage of the eligible population remains unscreened due to suboptimal screening compliance and the limitations of current modalities. The opportunity to improve CRC screening rates has driven research to develop novel screening approaches. Stool- and blood-based molecular tests have demonstrated significant potential for improving access to CRC screening.

     

Colorectal cancer screening awareness and intentions among low income, sociodemographically diverse adults under age 50

Colorectal cancer (CRC) screening rates in the US are suboptimal, particularly among lower income and racial/ethnically diverse groups. If specific populations have limited awareness of screening when they reach age 50, there may be delays in screening adoption. This study investigated sociodemographic and social contextual factors associated with awareness of CRC and intentions to be screened at age 50 among 692 low income, racial, and ethnic minority adults living in low income housing. The majority of respondents (62%) were between ages 30 and 49, and 94% had some form of health insurance (e.g., Medicaid). About 70% reported having heard about CRC screening; 66% reported intentions to be screened at age 50. In multivariable analyses, screening awareness was associated with age and education. Immigrants who had English as a second language had lower awareness. Females tended to have higher awareness if they had private insurance; there were no differences among males. Multivariable analyses found that screening intentions were higher among men, those with more role responsibilities, more role conflicts, and higher levels of social cohesion. It is important to identify opportunities for maximizing screening uptake among those who become age-eligible for screening if we are to make a significant impact on CRC disparities.     

Colorectal Cancer Screening among Asian Americans

Objectives: Colorectal cancer (CRC) is the most commonly diagnosed cancer for all US populations includingAsian Americans. CRC screening has considerable benefits to prevent CRC and reduce mortality. The purposeof this article was to review the published literature on rates of colorectal cancer screening and factors associatedwith colorectal cancer screening practice among Asian Americans. Methods: Through searching electronicreference databases from 2000 to 2013, 30 articles were found on Chinese, Filipino, Japanese, Korean, andVietnamese Americans. Findings: Asian Americans had significantly low ratesfor CRC screening; KoreanAmericans reported the lowest rates, while higher screening rates were found among Japanese Americans.Older age, longer length of stay in the US, and having a physician’s recommendation were the most commonfacilitators to receiving screening. The common inhibiting factors were financial issues, employment status,and worries/fears about the procedure. Conclusions: Despite a number of Asian Americans being vulnerableto CRC, individual Asian subgroups were underserved with CRC screening and intervention. Further studiesshould focus on each individual Asian subgroup and culturally proficient CRC screening intervention programsshould be developed for each.     

A simulation model for colorectal cancer screening: potential of stool tests with various performance characteristics compared with screening colonoscopy.

OBJECTIVE: Many new stool tests intended to detect neoplastic cells or cell products are developed at present for colorectal cancer (CRC) screening. The aim of this study was to simulate a population-based screening setting to assess and compare the potential for early detection and prevention of CRC of screening based on stool tests with different sensitivity and specificity and of screening with colonoscopy as a primary screening tool. METHOD: A Markov model was developed aimed to estimate the proportion of CRC cases which are early detected or prevented due to screening as well as the number of equired stool tests and colonoscopies per early detected or prevented CRC case. Model outcomes were calculated for the offer of annual stool testing from age 55 to 74 in combination with colonoscopic follow-up of positive test results and for the offer of screening colonoscopy as a primary screening tool at ages 55 and 65. The long-lasting risk reduction of colonoscopy allowing the removal of precancerous lesions was taken into account quantitatively. RESULTS: For a variety of stool tests with different performance characteristics, the proportion of CRC cases early detected or prevented was estimated to be higher for stool testing in combination with colonoscopic follow-up of positive test results compared with screening colonoscopy assuming levels of compliance to be expected for the respective screening scheme. Optimizing performance characteristics of stool tests in terms of detecting precancerous lesions, in addition to those in terms of detecting CRC, seemed to be crucial for maximizing effectiveness of CRC screening with stool tests. CONCLUSION: Screening based on new stool tests with colonoscopic follow-up of positive test results might offer a high potential for early detection or prevention of CRC.     

Evaluation of serum CEA,CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples

Background:

Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim of this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 for the early detection of CRC in an asymptomatic cohort.

Methods:

This nested case–control study within UKCTOCS used 381 serial serum samples from 40 women subsequently diagnosed with CRC, 20 women subsequently diagnosed with benign disease and 40 matched non-cancer controls with three to four samples per subject taken annually up to 4 years before diagnosis. CEA, CYFRA21-1 and CA125 were measured using validated assays and performance of markers evaluated for different pre-diagnosis time groups.

Results:

CEA levels increased towards diagnosis in a third of all cases (half of late-stage cases), whereas longitudinal profiles were static in both benign and non-cancer controls. At a threshold of >5 ng ml⁻¹ the sensitivities for detecting CRC up to 1 and 4 years before clinical presentation were 25% and 13%, respectively, at 95% specificity. At a threshold of >2.5 ng ml⁻¹, sensitivities were 57.5% and 38.4%, respectively, with specificities of 81% and 83.5%. CYFRA21-1 and CA125 had no utility as screening markers and did not enhance CEA performance when used in combination. CEA gave average lead times of 17–24 months for test-positive cases.

Conclusions:

CEA is elevated in a significant proportion of individuals with preclinical CRC, but would not be useful alone as a screening tool. This work sets a baseline from which to develop panels of biomarkers which combine CEA for improved early detection of CRC.     

Barriers and Facilitators to Colorectal Cancer Screening in South Asian Immigrants: A Systematic Review

Objective: The purpose of this systematic review is to broaden our knowledge of colorectal cancer (CRC) screening in South Asian immigrants living in Canada, Hong Kong, the United Kingdom, the United States, and Australia by determining the barriers and facilitators and examining interventions for CRC screening. Methods: A literature search of PubMed, Ovid Medline, and Google was conducted using South Asian, Asian Indians, cancer screening, colorectal neoplasm, early detection of cancer, and mass screening as search terms. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Only research articles written in English from 2000 to July 2022 were collected. Inclusion criteria included all English-language articles, the South Asian population, and either reporting barriers, facilitators, interventions, or recommendations for CRC screening. Exclusion criteria included all articles that did not meet inclusion criteria or were duplicates. A total of 32 articles were deemed eligible for inclusion and were retrieved for further analysis. The countries of origin in the articles reviewed included Canada, Hong Kong, the United Kingdom, the United States, and Australia. Results: In general, the studies indicated that South Asians have low CRC screening rates. The most common barriers reported were poor knowledge/awareness of CRC and CRC screening, lack of physician recommendation, psychological factors (e.g., fear, anxiety, and shame), cultural/religious factors, and sociodemographic factors (language barrier, lower income, and female gender). The most important facilitator reported was the physician’s recommendation. Six intervention studies of either education or organized screening programs were shown to have a positive influence by increasing knowledge and improving attitudes toward CRC screening. Conclusion: Of the limited number of studies identified, the population categorized as South Asians was largely heterogeneous, including a diversity of ethnicities. Although the rates of CRC among South Asians were relatively low, there remain many cultural barriers to the awareness of and screening for CRC in this population. Further research in this population is needed to better identify the factors related to CRC in individuals of South Asian ethnicity. Recommending CRC screening by physicians and mid-level providers and educating patients with culturally sensitive programs and materials are important to increase knowledge and awareness of CRC and CRC screening.     

Molecular tests for colorectal cancer screening

Detecting and removing high-risk adenomas and early colorectal cancer (CRC) can reduce mortality of this disease. The noninvasive fecal occult blood test (FOBT; guaiac-based or immunochemical) is widely used in screening programs and although effective, it leaves room for improvement in terms of test accuracy. Molecular tests are expected to be more sensitive, specific and informative than current detection tests, and are promising future tools for CRC screening. This review provides an overview of the performances of DNA, RNA, and protein markers for CRC detection in stool and blood. Most emphasis currently is on DNA and protein markers. Among DNA markers there is trend to move away from mutation markers in favor of methylation markers. The recent boost in proteomics research leads to many new candidate protein markers. Usually in small series, some markers show better performance than the present FOBT. Evaluation in large well-controlled randomized trials is the next step needed to take molecular markers for CRC screening to the next level and warrant implementation in a screening setting.     

Overuse ofcolorectal cancer screening services inthe United States andits implications

As a standard way for prevention and early detection of colorectal cancer (CRC), colonoscopy has been used for CRC screening in the United States for more than one decade. An article entitled “Assessing Colorectal Cancer Screening Adherence of Medicare Fee-For-Service Beneifciaries Age 76 to 95 Years” recently published at theJournal of Oncology Practice reports the trends in overuse of CRC screening services among average-risk elderly populations at the age of 76–95years. Several reasons for overusing colonoscopy have been postulated, and some strategies for reducing overuse of CRC screening services have also been proposed.     

Colorectal Cancer Screening: Patients' and Physicians' Perspectives on Decision-Making Factors

While patient barriers to colorectal cancer (CRC) screening have been identified, how well this knowledge is utilized during the patient–physician interaction is not fully understood. This study aims to assess among primary care physicians the degree of consensus between perceived and actual patients' CRC screening decision-making influential factors. During 2004–2006, 30 patients were interviewed to identify factors influencing screening decisions and 66 physicians were interviewed to understand what factors they thought were important to patients. The factors were categorized using the PRECEDE–PROCEED framework, and perspectives were compared. The researchers found little consensus on CRC screening decision-making influential factors between family practitioners, general internists, and patients. The recommendations to reach consensus are provided on the individual (e.g., updating the contents of a physician's screening recommendation to proactively address patients' decision-making needs) and population (e.g., providing cross-cultural training to medical students enabling them to better understand their patients) levels.     

Continuity of Care and Colorectal Cancer Screening by Vietnamese American Patients

Background: Colorectal cancer (CRC) screening rates among Asian Americans are 30-50% lower than among Whites. Using practice management and electronic medical records data from a community health center, we examined the association of CRC screening with continuity of care and comorbidity. These variables have not previously been studied in Asian American and limited-English proficient populations. Methods: After obtaining IRB approval, we extracted data in 2009 on age-eligible Vietnamese patients who had one or more clinic visits in the prior 24 months. Our analysis examined associations between CRC screening (per current US Preventive Services Task Force guidelines) and clinic site, demographics, insurance status, continuity of care, comorbidities, and provider characteristics. Results: We identified a total of 1,016 eligible patients (604 at Clinic 1 and 412 at Clinic 2). Adherence to CRC screening was lower for patients who were male; lacked insurance; had only one medical visit in the past 12 months; and had no assigned primary care provider. Our multivariable models showed higher screening rates among patients who were female; had public health insurance; and had more than one medical visit in the past 12 months, regardless of “high” or “low” continuity of care. Conclusions: We found no association between higher continuity of care and CRC screening. Additional primary care systems research is needed to guide cancer screening interventions for limited-English proficient patients.     

Stool test for colorectal cancer screening: what is going on?

Given the increasing incidence of colorectal cancer (CRC), performing new and cost-effective stool tests is of particular importance for early diagnosis and treatment. In the present review, we describe the main characteristics, and the performance of the most recently developed stool tests in the screening setting of colorectal tumoral diseases. Most of the studies reported high sensitivity both for adenomas and CRC diagnosis; less than half studies reported also high specificity with respect to stage and localization of the tumor. However, the performance of every single test was extremely variable, reaching >95% specificity for most of DNA-based markers, although lacking sensitivity even in case of invasive CRC. A new potential stool marker of colon cancer is clusterin, a protein of particular interest for its high sensitivity and positive predictive value in patients with highly aggressive CRC.     

Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications

Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers’ assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.     

Breath testing as potential colorectal cancer screening tool

Although colorectal cancer (CRC) screening is included in organized programs of many countries worldwide, there is still a place for better screening tools. In this study, 418 breath samples were collected from 65 patients with CRC, 22 with advanced or nonadvanced adenomas, and 122 control cases. All patients, including the controls, had undergone colonoscopy. The samples were analysed with two different techniques. The first technique relied on gas chromatography coupled with mass spectrometry (GC‐MS) for identification and quantification of volatile organic compounds (VOCs). The T‐test was used to identify significant VOCs (p values < 0.017). The second technique relied on sensor analysis with a pattern recognition method for building a breath pattern to identify different groups. Blind analysis or leave‐one‐out cross validation was conducted for validation. The GC‐MS analysis revealed four significant VOCs that identified the tested groups; these were acetone and ethyl acetate (higher in CRC), ethanol and 4‐methyl octane (lower in CRC). The sensor‐analysis distinguished CRC from the control group with 85% sensitivity, 94% specificity and 91% accuracy. The performance of the sensors in identifying the advanced adenoma group from the non‐advanced adenomas was 88% sensitivity, 100% specificity, and 94% accuracy. The performance of the sensors in identifying the advanced adenoma group was distinguished from the control group was 100% sensitivity, 88% specificity, and 94% accuracy. For summary, volatile marker testing by using sensor analysis is a promising noninvasive approach for CRC screening.     

Analyzing factors enabling colorectal cancer screening adherence in Korean Americans using the Andersen's Behavioral Model of Health Services Utilization

Abstract

Purpose/objectives: Korean Americans (KAs) report suboptimal colorectal cancer (CRC) screening adherence. This study investigated factors that enable KAs to adhere to CRC screening guidelines using the Andersen's Behavioral Model of Health Services Utilization.

Design: Cross-sectional survey using self-reported measures of CRC screening behaviors.

Sample and methods: Purposive sampling was used to recruit 433 KAs aged 50–75 from the Atlanta metropolitan area who completed questionnaires measuring predisposing (i.e., gender, age, marital status, and educational attainment), enabling (income, health insurance, regular annual health checkups, doctor's recommendation English proficiency, CRC knowledge, self-efficacy for CRC screening, and decisional balance in CRC screening), and need (family cancer history and self-reported health status) factors associated with CRC screening.

Findings: A multiple logistic regression model including all 14 predictor variables revealed that several enabling factors (i.e., income, regular annual health checkups, doctor’s recommendation, self-efficacy, and decisional balance) independently predicted increased CRC screening adherence in KAs. No predisposing or need factors independently predicted CRC screening.

Conclusions and implications for psychosocial providers or policy: To increase CRC screening adherence among KAs, psychosocial interventions should target on improving their self-efficacy and decisional balance regarding CRC screening, while policy interventions should focus on promoting health providers’ CRC screening recommendations during routine health checkups.     

Mobile Health Interventions for Improving Colorectal Cancer Screening Rates: A Systematic Review and Meta-Analysis

Objective: The aim of this systematic review and meta-analysis was to determine the efficacy of different mHealth interventions in increasing colorectal cancer (CRC) screening rates. Methods: A literature search for eligible studies was done in ClinicalTrials.gov, PubMed, and Scopus in October 2020. Included studies were randomized controlled trials done on adults due for CRC screening, who received either an mHealth intervention to promote screening or usual care. The primary outcome from these studies was completion of CRC screening. Two reviewers independently worked on selecting studies, collecting data, and determining risk of bias. Adjusted odds ratios (AOR) for CRC screening rates were summarized into a Forest plot. Results: A total of ten trials from three continents were included in the qualitative analysis. Risk of bias is low in terms of randomization, but high in terms of participant blinding, due to the nature of the interventions. Meta-analysis of four trials showed low clinical and statistical heterogeneity (I2=0%). Overall, the use of mHealth interventions is associated with higher CRC screening uptake when compared to usual care (AOR 1.33; 95% CI, 1.20-1.46). This effect was seen across different types of mHealth interventions, which included automated and non-automated telephone education and text-message reminders. Conclusion: This study showed that mHealth is associated with increased CRC screening participation regardless of the type of intervention used.     

MTHFR C677T and colorectal cancer risk: A meta-analysis of 25 populations

The common functional methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may influence the risk of colorectal cancer (CRC), but data from published studies with individually low statistical power are conflicting. To clarify the role of MTHFR C677T genotype in CRC, we considered all available studies in a meta-analysis. Studies reporting on MTHFR C677T genotype and CRC were searched in PubMed up to April 2006. The principle prior hypothesis was that homozygosity for MTHFR 677TT would be associated with reduced risk of CRC. Data were available for 29,931 subjects, including 12,243 with CRC, from 25 independent populations. Compared to the homozygous CC genotype, the MTHFR 677TT genotype was associated with a reduced risk of CRC (odds ratio (OR): 0.83; 95% confidence interval (CI): 0.75-0.93; p = 0.001). There was some heterogeneity among the results of individual studies, but this was not statistically significant (heterogeneity p = 0.12; I2 = 25.8%). Heterozygosity for MTHFR 677 did not influence CRC risk (OR: 0.99; 95% CI: 0.94-1.04). These findings indicate that individuals homozygous for the MTHFR 677TT genotype are at moderately reduced risk of CRC, and support the proposal that common genetic variation in the MTHFR gene contributes to CRC susceptibility, probably accounting for at least 9% of the total incidence.