Improving colorectal cancer screening programs.

In this editorial we comment on the article by Agatsuma et al published in the World Journal of Gastroenterology. They suggest policies for more effective colorectal screening. Screening is the main policy that has led to lower mortality rates in later years among the population that was eligible for screening. Colonoscopy is the gold standard tool for screening and has preventive effects by removing precancerous or early malignant polyps. However, colonoscopy is an invasive process, and fecal tests such as the current hemoglobin immunodetection were developed, followed by endoscopy, as the general tool for population screening, avoiding logistical and economic problems. Even so, participation and adherence rates are low. Different screening options are being developed with the idea that if people could choose between the ones that best suit them, participation in population-based screening programs would increase. Blood tests, such as a recent one that detects cell-free DNA shed by tumors called circulating tumor DNA, showed a similar accuracy rate to stool tests for cancer, but were less sensitive for advanced precancerous lesions. At the time when the crosstalk between the immune system and cancer was being established as a new hallmark of cancer, novel immune system-related biomarkers and information on patients' immune parameters, such as cell counts of different immune populations, were studied for the early detection of colorectal cancer, since they could be effective in asymptomatic people, appearing earlier in the adenoma-carcinoma development compared to the presence of fecal blood. sCD26, for example, detected 80.37% of advanced adenomas. To reach as many eligible people as possible, starting at an earlier age than current programs, the direction could be to apply tests based on blood, urine or salivary fluid to samples taken during routine visits to the primary health system.

[Colorectal cancer in 45-49-year-olds: systematic or targeted screening?] / Cancer du côlon chez les 45-49 ans : dépistage systématique ou ciblé ?

Principles to guide and inform population-based screening decisions cover a wide range of aspects beyond the screening test. Colorectal cancer (CRC) meets these requirements for individuals at moderate risk aged 50 to 69. In Switzerland, screening using a biennial faecal occult blood test or colonoscopy every 10 years is reimbursed free of deductible in 12 programs covering 15 cantons. This article assesses the appropriateness of systematic screening from age 45 in the Swiss context. Prioritizing measures to raise awareness among healthcare professionals and high-risk subjects rather than lowering the age of eligibility would not only be more sensible but would also benefit to the population over 50 years old.

Les critères pour proposer un dépistage organisé couvrent de nombreuses dimensions, au-delà des caractéristiques du test de dépistage. Le cancer colorectal (CCR) répond à ces exigences pour les personnes à risque modéré de 50 à 69 ans. En Suisse, un dépistage par un test biennal de détection de sang occulte dans les selles ou par coloscopie tous les 10 ans est remboursé hors franchise dans 12 programmes couvrant 15 cantons. Cet article fait le point de la situation concernant l'adéquation d'un dépistage organisé du CCR dès 45 ans dans le contexte suisse. Prioriser des mesures de sensibilisation auprès des professionnel-le-s de santé et des sujets à haut risque de CCR serait non seulement plus judicieux que d'abaisser l'âge d'éligibilité au dépistage organisé mais bénéficierait aussi à la population de plus de 50 ans.

Colorectal cancer screening: Modalities and adherence.

In the last decade, several studies have explored various modalities and strategies for colorectal cancer (CRC) screening, taking into account epidemiological data, individual characteristics, and socioeconomic factors. In this editorial, we comment further on a retrospective study by Agatsuma et al published in the recent issue of the World Journal of Gastroenterology. Our focus is on screening trends, particularly in relation to efforts to improve the currently suboptimal uptake among the general population worldwide, aiming to enhance early diagnosis rates of CRC. There is a need to raise awareness through health edu-cation programs and to consider the use of readily available, non-invasive screening methods. These strategies are crucial for attracting screen-eligible populations to participate in first-line screening, especially those in high- or average-risk groups and in regions with limited resources. Liquid biopsies and biomarkers represent rapidly evolving trends in screening and diagnosis; however, their clinical relevance has yet to be standardized.

Advancing Colorectal Cancer Detection With Blood-Based Tests: Qualitative Study and Discrete Choice Experiment to Elicit Population Preferences.

BACKGROUND: Colorectal cancer (CRC) is the second most deadly form of cancer, inducing an estimated 1.9 million incidence cases and 0.9 million deaths worldwide in 2020. Despite the availability of screening tests, their uptake remains suboptimal. However, blood-based tests that look for signs of cancer-specific markers in the body are increasingly available as an alternative for more invasive tests for cancer. Compared with existing tests, the benefits of blood-based tests for CRC include not needing pretest preparation, stool handling, and dietary or medication restrictions. OBJECTIVE: This study aims to explore the population's preferences for CRC screening tests, with a focus on blood-based tests, and investigate the factors influencing test uptake. METHODS: We used a mixed methods approach, combining semistructured interviews and a discrete choice experiment (DCE) survey. Interviews were analyzed using thematic analysis to identify salient attributes for CRC screening tests. These attributes informed the design of the DCE survey. The DCE data were analyzed using mixed logit and mixed-mixed multinomial logit models. RESULTS: Qualitative findings from 30 participants revealed that participants preferred blood-based tests due to their perceived low risk, minimal pain, and ease of sample collection. However, concerns about the test's lower accuracy were also expressed. The DCE survey was completed by 1189 participants. In the mixed logit model, participants demonstrated a stronger preference for blood-based tests over a 2-day stool-based test. The mixed-mixed multinomial logit model identified 2 classes, strong supporters and weak supporters, for CRC screening. Weak supporters, but not strong supporters, had a higher preference for blood-based tests. Women, ethnic Chinese, and people aged 40 to 60 years were more likely to be weak supporters. Both models highlighted the high influence of cost and test sensitivity on participants' preferences. Transitioning from a 2-day stool-based test to a blood-based test, assuming a national screening program at a base price of Singapore $5 (US $3.75), was estimated to have the potential to increase the relative uptake by 5.9% (95% CI 3.6%-8.2%). CONCLUSIONS: These findings contribute to our understanding of CRC screening preferences and provide insights into the factors driving test uptake. This study highlights the perceived advantages of blood-based tests and identifies areas of concern regarding their accuracy. Further research is needed to determine the actual increase in uptake rate when blood-based tests are made available.

Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death.

Importance: The fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening, but evidence of its effectiveness is limited. Objective: To evaluate whether FIT screening is associated with a lower risk of dying from CRC overall, according to cancer location, and within demographic groups. Design, Setting, and Participants: This nested case-control study in a cohort of screening-eligible people was conducted in 2 large, integrated health systems of racially, ethnically, and socioeconomically diverse members with long-term programs of mailed FIT screening outreach. Eligible participants included people aged 52 to 85 years who died from colorectal adenocarcinoma between 2011 and 2017 (cases); cases were matched in a 1:8 ratio based on age, sex, health-plan membership duration, and geographic area to randomly selected persons who were alive and CRC-free on case's diagnosis date (controls). Data analysis was conducted from January 2002 to December 2017. Exposures: Completing 1 or more FIT screenings in the 5-year period prior to the CRC diagnosis date among cases or the corresponding date among controls; in secondary analyses, 2- to 10-year intervals were evaluated. Main Outcomes and Measures: The primary study outcome was CRC death overall and by tumor location. Secondary analyses were performed to assess CRC death by race and ethnicity. Results: From a cohort of 2 127 128 people, a total of 10 711 participants (3529 aged 60-69 years [32.9%]; 5587 male [52.1%] and 5124 female [47.8%]; 1254 non-Hispanic Asian [11.7%]; 973 non-Hispanic Black [9.1%]; 1929 Hispanic or Latino [18.0%]; 6345 non-Hispanic White [59.2%]) was identified, including 1103 cases and 9608 controls. Among controls during the 10-year period prior to the reference date, 6101 (63.5%) completed 1 or more FITs with a cumulative 12.6% positivity rate (768 controls), of whom 610 (79.4%) had a colonoscopy within 1 year. During the 5-year period, 494 cases (44.8%) and 5345 controls (55.6%) completed 1 or more FITs. In regression analysis, completing 1 or more FIT screening was associated with a 33% lower risk of death from CRC (adjusted odds ratio [aOR], 0.67; 95% CI, 0.59-0.76) and 42% lower risk in the left colon and rectum (aOR, 0.58; 95% CI, 0.48-0.71). There was no association with right colon cancers (aOR, 0.83; 95% CI, 0.69-1.01) but the difference in the estimates between the right colon and left colon or rectum was statistically significant (P = .01). FIT screening was associated with lower CRC mortality risk among non-Hispanic Asian (aOR, 0.37; 95% CI, 0.23-0.59), non-Hispanic Black (aOR, 0.58; 95% CI, 0.39-0.85) and non-Hispanic White individuals (aOR, 0.70; 95% CI, 0.57-0.86) (P for homogeneity = .04 for homogeneity). Conclusions and Relevance: In this nested case-control study, completing FIT was associated with a lower risk of overall death from CRC, particularly in the left colon, and the associations were observed across racial and ethnic groups. These findings support the use of FIT in population-based screening strategies.

Modelling the impact of bias in fecal immunochemical testing on long-term outcomes of colorectal cancer screening.

BACKGROUND: As the impact of unmanaged bias (i.e. systematic source of inaccuracy) in fecal immunochemical test (FIT) analytical performance on long-term colorectal cancer (CRC) outcomes is unknown, we assessed the impact bias in FIT performance in an ongoing FIT-based CRC screening program. METHODS: This study consisted of two parts: cross-sectional observational data analysis to estimate change in short-term outcomes and microsimulation modelling to estimate change in long-term outcomes assuming different levels of bias by assuming 15 % lower up to 15 % higher Hemoglobin detected in the stool compared to observed. Two scenarios were considered: bias occurring 1) one-time only, due to the occasional bias associated with the FIT kits used in 2020 and 2) consistently due to a constant bias associated with the FIT kits used from 2020 onwards. RESULTS: With a hypothetical bias of -15 % to +15 %, we observed a positivity rate ranging from 6.7 % to 7.8 %, and a detection rate for CRC between 0.65 % and 0.68 %. Single biases in FIT performance resulted in less than 0.1 % change in long-term CRC screening outcomes, while consistent biases resulted in a much larger change (up to 1.4 % in CRC cases and CRC-related deaths and up to 2.07 % in total costs). Detecting lower Hemoglobin concentrations resulted in a relatively larger change on long-term CRC outcomes in comparison to positive bias. CONCLUSIONS: Because of the substantial impact of consistent FIT bias, it is important to set evidence-based acceptance criteria of bias on long-term CRC screening outcomes and in particular, the introduction of an asymmetrical or upward shifted tolerance interval for FIT bias.

Colonoscopy findings after increasing two-stool faecal immunochemical test (FIT) cut-off: Cross-sectional analysis of the SCREESCO randomized trial.

BACKGROUND: We determined the impact of an increased two-stool faecal immunochemical test (FIT) cut-off on colonoscopy positivity and relative sensitivity and specificity in the randomized controlled screening trial screening of Swedish colons conducted in Sweden. METHODS: We performed a cross-sectional analysis of participants in the FIT arm that performed FIT between March 2014 and 2020 within the study registered with ClinicalTrials.gov, NCT02078804, who had a faecal haemoglobin concentration of at least 10 µg/g in at least one of two stool samples and who underwent a colonoscopy (n = 3841). For each increase in cut-off, we computed the positive predictive value (PPV), numbers needed to scope (NNS), sensitivity and specificity for finding colorectal cancer (CRC) and advanced neoplasia (AN; advanced adenoma or CRC) relative to cut-off 10 µg/g. RESULTS: The PPV for AN increased from 23.0% (95% confidence intervals [CI]: 22.3%-23.6%) at cut-off 10 µg/g to 28.8% (95% CI: 27.8%-29.7%) and 33.1% (95% CI: 31.9%-34.4%) at cut-offs 20 and 40 µg/g, respectively, whereas the NNS to find a CRC correspondingly decreased from 41 to 27 and 19. The PPV for AN was higher in men than women at each cut-off, for example 31.5% (95% CI: 30.1%-32.8%) in men and 25.6% (95% CI: 24.3%-27.0%) in women at 20 µg/g. The relative sensitivity and relative specificity were similar in men and women at each cut-off. CONCLUSION: A low cut-off of around 20-40 µg/g allows detection and removal of many AN compared to 10 µg/g while reducing the number of colonoscopies in both men and women.

Faecal Immunochemical Test (FIT) Sensitivity; A Five Year Audit.

Introduction: Colorectal cancer has a high prevalence and mortality rate in the United Kingdom. Cancerous colorectal lesions often bleed into the gastrointestinal lumen. The faecal immunochemical test (FIT) detects haemoglobin (Hb) in the faeces of patients and is used as a first line test in the diagnosis of colorectal cancer. Materials and Methods: A retrospective audit of all FIT performed and all colorectal cancers diagnosed in the Hull and East Riding of Yorkshire counties of the United Kingdom (population approximately 609,300) between 2018 and 2022 was conducted. FIT were performed using a HM-JACKarc analyser from Kyowa medical. The predominant symptom suggestive of colorectal cancer which prompted the FIT was recorded. Colorectal cancer was diagnosed using the gold standard of histological biopsy following colonoscopy. Results: Between 2018 and 2022, 56,202 FIT were performed on symptomatic patients. Follow on testing identified 1,511 with colorectal cancer. Of these people, only 450 people with a confirmed colorectal cancer had a FIT within the 12 months preceding their diagnosis. Of these 450 FIT results, 36 had a concentration of <10 µg/g and may be considered to be a false negative. The sensitivity of FIT in the patients identified was 92.00%. The most common reason stated by the clinician for a FIT being performed in patients with colorectal cancer was a change in bowel habits, followed by iron deficient anaemia. The number of patients diagnosed with colorectal cancer decreased in 2020, but increased significantly in 2021. Discussion: This study shows that 8.00% of people diagnosed with colorectal cancer in the Hull and East Riding of Yorkshire regions had a negative FIT. This study also shows that the SARS-CoV-2 pandemic affected the number of people diagnosed with colorectal cancer, and therefore skews the prevalence and pre-test probability of a positive test. There are many reasons why a FIT could produce a false negative result, the most likely being biological factors affecting the stability of haemoglobin within the gastrointestinal tract, or pre-analytical factors influencing faecal sampling preventing the detection of haemoglobin. Some colorectal lesions do not protrude into the gastrointestinal lumen and are less likely to bleed. Conclusion: This is the first study showing data from outside of a structured clinical trial and provides the largest study to date showing the sensitivity of FIT in a routine clinical setting. This study also provides evidence for the impact COVID-19 had on the rate of colorectal cancer diagnosis.

Predictive values of an immunological fecal occult blood test for the diagnosis of colorectal cancer compared using colonoscopy in symptomatic patients in Yaounde (Cameroon).

INTRODUCTION: The predictive value of immunological fecal occult blood (iFOB) testing for the screening of colorectal cancer has been well described in the Western world. However, its relevance in Sub-Saharan Africa (SSA) is not well evaluated. It could be altered by the other causes of lower gastrointestinal bleeding such as parasitic infections. The aim of this study was to highlight the performance of an iFOB test for the prediction of colorectal cancer (CRC) during colonoscopy in SSA. METHODOLOGY: We conducted an analytical cross-sectional study in two digestive endoscopic centers of Yaoundé (Cameroon) from the 1st July to the 31 November 2022. Patients presenting with an indication for colonoscopy without any overt gastrointestinal bleeding were included. Sociodemographic and clinical data were collected. All consenting patients underwent a qualitative immunologic occult test through the iFOB test before colonoscopy. Data were analyzed using SPSS version 23.0 software. The performance of the iFOB test for the diagnosis of CRC during colonoscopy was evaluated in terms of sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). RESULTS: We included 103 patients during the study period with a male predominance and a sex ratio of 1.7. The median age [IQR] was 52 [38-65] years (range 1 - 84 years). The most common colonoscopic lesions were polyps in 23 patients (22.3%), CRC in 17 patients (16.5%) and hemorrhoids in 15 patients (14.6%). Patients testing positive for iFOB test accounted for 43.7% (45 patients). Among these patients, 31.1% (14 patients) had a CRC. The Se of the occult blood test for CRC detection was calculated to be 82.3% (95%CI: 56.7-96.2); the Sp was 63.9% (95% CI: 53-74); the PPV was 31.1% (95% CI: 24-39) and the NPV was 94.8% (95% CI: 86.6-98.1). CONCLUSION: The iFOB test has a good NPV, but a poor PPV for the diagnosis of CRC in our study.

Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: inequities in diagnostic yield.

BACKGROUND: Socioeconomic inequalities in the uptake of colorectal cancer screening are well documented, but the implications on inequities in health gain remain unclear. METHODS: Sixty-year-olds were randomly recruited from the Swedish population between March 2014 and March 2020 and invited to undergo either 2 rounds of fecal immunochemical testing (FIT) 2 years apart (n = 60 137) or primary colonoscopy just once (n = 30 400). By linkage to Statistics Sweden's registries, we obtained socioeconomic data. In each defined socioeconomic group, we estimated the cumulative yield of advanced neoplasia in each screening arm (intention-to-screen analysis). In the biennial FIT arm, we predicted the probability of exceeding the yield in the primary colonoscopy arm by linear extrapolation of the cumulative yield to (hypothetical) additional rounds of FIT. RESULTS: In the lowest income group, the yield of advanced neoplasia was 1.63% (95% confidence interval [CI] = 1.35% to 1.93%) after 2 rounds of FIT vs 1.93% (95% CI = 1.49% to 2.40%) in the primary colonoscopy arm. Extrapolation to a third round of FIT implied a 86% probability of exceeding the yield in the primary colonoscopy arm. In the highest income group, we found a more pronounced yield gap between the 2 screening strategies-2.32% (95% CI = 2.15% to 2.49%) vs 3.71% (95% CI = 3.41% to 4.02%)- implying a low (2%) predicted probability of exceeding yield after a third round of FIT. CONCLUSIONS: Yield of advanced neoplasia from 2 rounds of FIT 2 years apart was poorer as compared with primary colonoscopy, but the difference was less in lower socioeconomic groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02078804.

Comparing the effectiveness and cost-effectiveness of text-message reminders and telephone patient navigation to improve the uptake of faecal immunochemical test screening among non-responders in London: a randomised controlled trial protocol.

INTRODUCTION: Participation in bowel cancer screening is lower in regions where there is high ethnic diversity and/or socioeconomic deprivation. Interventions, such as text message reminders and patient navigation (PN), have the potential to increase participation in these areas. As such, there is interest in the comparative effectiveness of these interventions to increase bowel cancer screening participation, as well as their relative cost-effectiveness. METHODS AND ANALYSIS: This study will use a three-arm randomised controlled trial design to compare the effectiveness and cost-effectiveness of text message reminders and PN to increase the uptake of bowel cancer screening in London. Participants will be individuals who have not returned a completed faecal immunochemical test kit within 13 weeks of receiving a routine invitation from the London bowel cancer screening hub. Participants will be randomised (in a 1:1:1 ratio) to receive either (1) usual care (ie, 'no intervention'), (2) a text message reminder at 13 weeks, followed by repeated text message reminders at 15, 17 and 19 weeks (in the event of non-response) or (3) a text message reminder at 13 weeks, followed by PN telephone calls at 15, 17 and 19 weeks in the event of non-response. The primary endpoint will be participation in bowel cancer screening, defined as 'the return of a completed kit by week 24'. Statistical analysis will use multivariate logistic regression and will incorporate pairwise comparisons of all three groups, adjusted for multiple testing. ETHICS AND DISSEMINATION: Approvals to conduct the research have been obtained from University College London's Joint Research Office (Ref: 150666), the Screening Research, Innovation and Development Advisory Committee ('RIDAC', Ref: 2223 014 BCSP Kerrison), the Health Research Authority (Ref: 22/WM/0212) and the Confidentiality Advisory Group (Ref: 22/CAG/0140). Results will be conveyed to stakeholders, notably those managing the screening programme and published in peer-reviewed journals/presented at academic conferences. TRIAL REGISTRATION NUMBER: ISRCTN17245519.

Colorectal Cancer Screening in Free Clinics: A Systematic Review.

OBJECTIVE: There are significant inequities in colorectal cancer (CRC) screening and outcomes. Via literature review, we assessed CRC screening rates for the vulnerable populations served by free clinics. METHODS: A systematic review was conducted for publications on CRC screening in free clinics. Outcomes included CRC screening characteristics, population demographics, and limitations. A methodological quality assessment was completed. RESULTS: Out of 63 references, six studies were included, representing 8,844 participants. Black or Hispanic participants were the plurality in all but one study. All participants were uninsured. Median CRC screening rate was 48.4% (range 6.6-78.9%). Screening methods included colonoscopy, fecal occult blood test, flexible sigmoidoscopy, and fecal immunochemical test. Clinics offering only one screening method had a mean screening rate of 7.2% while those with multiple methods had a screening rate of 65.4%. CONCLUSION: Access to multiple CRC screening modalities correlates with higher screening rates in free clinics. More work is needed to increase CRC screening in free clinics.

Lowering Fecal Immunochemical Test Positivity Threshold vs Multitarget Stool RNA Testing for Colorectal Cancer Screening.

This analysis uses data from 2 studies to explore whether lowering the threshold for fecal immunochemical test positivity can achieve comparable levels of sensitivity and specificity as multitarget stool RNA testing for colorectal cancer screening.