The evidence on the cumulative participation and yield in multiple rounds of colorectal cancer (CRC) screening based on fecal immunochemical test is sparse. We aimed to assess the trends in participation and detection for advanced colorectal neoplasm under different screening intervals in multiround fecal immunochemical testing-based CRC screening by synthesizing the current available evidence.

PubMed, Embase, and Cochrane were retrieved from January 1, 2002, to April 16, 2024, for potential eligible studies, and then, we synthesized participation and advanced colorectal neoplasm detection rates for each screening round, along with their respective 95% confidence intervals (CIs).

Nineteen studies involving a total of 2,296,071 individuals were included. As screening rounds increased, participation exhibited a gradual consistent increase, reaching 78.45% and 74.97% for annual and biennial screening strategies. For annual screening, the cumulative detection rates for 3 rounds were 1.38% (95% CI: 1.18%-1.63%), 1.95% (95% CI: 1.72%-2.21%), and 2.50% (95% CI: 2.29%-2.72%), respectively. For biennial screening, the cumulative detection rates for 4 rounds were 2.22% (95% CI: 1.22%-3.22%), 3.44% (95% CI: 2.06%-4.82%), 4.26% (95% CI: 2.70%-5.83%), and 5.10% (95% CI: 3.28%-7.29%), respectively. Notably, the per-round detection rate of advanced colorectal neoplasms declined yet as the screening progressed.

In population-based CRC screening programs, the participation exhibited a slow upward trend for both screening strategies, but the incremental benefits in CRC detection gradually diminished. Tailored strategies, such as extending intervals for individuals with multiple negative fecal immunochemical testing results, might optimize effectiveness and cost-efficiency in population-based CRC screening.

Adenoma detection rate (ADR) is a quality indicator set at a minimum of 25% in unselected populations by the European Society of Gastrointestinal Endoscopy (ESGE). Nevertheless, a lack of pooled observational data resembling real-world practice limits support for this threshold. We aimed to perform a systematic review with meta-analysis to evaluate the pooled rates for conventional adenoma detection, polyp detection (PDR), cecal intubation, bowel preparation, and complications in population-based studies.

The PubMed, Scopus, and Web of Science databases were searched until May 2023 for populational-based studies reporting overall ADR in unselected individuals. A random-effects model was used for meta-analysis.

31 studies were included, comprising 3 644 561 subjects. A high quality of procedures was noticeable, with a high cecal intubation rate and low complication rate. The overall pooled ADR, PDR, and rate of cancer detection were 26.5% (95%CI 23.3% to 29.7%), 38.3% (95%CI 32.5% to 44.1%), and 2.7% (95%CI 1.5% to 3.9%), respectively. ADR varied according to indication: screening 33.3% (95%CI 24.5% to 42.2%), surveillance 42.9% (95%CI 36.9% to 49.0%), and diagnostic 24.7% (95%CI 19.5% to 29.9%), with subgroup analysis revealing rates of 34.4% (95%CI 22.0% to 40.5%) for post-fecal occult blood test and 26.6% (95%CI 22.6% to 30.5%) for primary colonoscopy screening. Diminutive conventional adenomas yielded a pooled rate of 59.9% (95%CI 43.4% to 76.3%). The pooled rate for overall serrated lesion detection was 12.4% (95%CI 8.8% to 16.0%). Male sex and higher age were significantly associated with an ADR above the benchmark.

This first meta-analysis relying on real-world observational studies supports the ESGE benchmark for ADR, while suggesting that different benchmarks might be used according to indication, sex, and age.

Fecal occult blood test (FOBT) and fecal immunohistochemical test (FIT) are used for colorectal cancer (CRC) screening. However, when no adenomas are found following a positive FOBT/FIT, the future risk of advanced adenomas or colorectal cancer (CRC) is unclear. We determined the incidence and determinants of advanced adenomas or CRC after a negative index colonoscopy following a positive FOBT/FIT.

We identified patients in the Harris Health System (Houston, Texas) who underwent a colonoscopy following a positive FOBT/FIT from 01/2010 to 01/2013. We compared the incidence rates of advanced adenomas (≥ 1 cm, villous histopathology, or high-grade dysplasia) or CRC through 12/2023 for patients without polyps on index colonoscopy (negative colonoscopy) to patients with polyps (positive colonoscopy). We examined risk factors for incident adenomas using Cox regression models.

Of 2096 patients, 1293 (61.7%) had negative index colonoscopy and 803 (38.3%) had positive index colonoscopy. Overall, 411 patients (19.6%) underwent subsequent colonoscopy with incident adenomas in 241 patients and no incident CRC over mean 12.5 years. The incidence rate of advanced adenomas was 2.08 per 100 person-years after positive index colonoscopy compared to 0.65 per 100 person-years after negative index colonoscopy (age-adjusted incidence rate ratio 3.08, 95% CI 1.27-7.48). Non-Hispanic white race was the strongest risk factor for incident adenomas among patients with negative index colonoscopy.

We found a low likelihood of advanced adenomas and no interval CRC following negative index colonoscopy after positive FOBT/FIT. Non-Hispanic white race was a risk factor for incident adenomas, and these patients may warrant closer surveillance.

Colorectal cancer (CRC) is a significant global health issue where early detection is crucial for improving treatment outcomes and survival rates. This comprehensive review assesses the utility of stool-based tests in CRC screening, including traditional fecal occult blood tests (FOBT), both chemical (gFOBT) and immunochemical techniques (FIT), as well as multitarget stool DNA (mt-sDNA) as a novel and promising biomarker. The advancements, limitations and the impact of false positives and negatives of these methods are examined. The review analyzed various studies on current screening methods, focusing on laboratory tests and biomarkers. Findings indicate that while FIT and mt-sDNA tests offer enhanced sensitivity and specificity over traditional guaiac-based FOBT, they also come with higher costs and potential for increased false positives. FIT shows better patient adherence due to its ease to use, but incorrect usage and interpretation of FOBT can lead to significant diagnostic errors. In conclusion, despite the improvements in FOBT methods like FIT in CRC detection, careful consideration of each method's benefits and drawbacks is essential. Effective CRC screening programs should combine various methods tailored to specific population needs, aiming for early detection and reduced mortality rates.

Observational studies are frequently used to estimate the comparative effectiveness of different colorectal cancer (CRC) screening methods due to the practical limitations and time needed to conduct large clinical trials. However, time-varying confounders, e.g. polyp detection in the last screening, can bias statistical results. Recently, generalized methods, or G-methods, have been used for the analysis of observational studies of CRC screening, given their ability to account for such time-varying confounders. Discretization, or the process of converting continuous functions into discrete counterparts, is required for G-methods when the treatment and outcomes are assessed at a continuous scale.

This paper evaluates the interplay between time-varying confounding and discretization, which can induce bias in assessing screening effectiveness. We investigate this bias in evaluating the effect of different CRC screening methods that differ from each other in typical screening frequency.

First, using theory, we establish the direction of the bias. Then, we use simulations of hypothetical settings to study the bias magnitude for varying levels of discretization, frequency of screening and length of the study period. We develop a method to assess possible bias due to coarsening in simulated situations.

The proposed method can inform future studies of screening effectiveness, especially for CRC, by determining the choice of interval lengths where data are discretized to minimize bias due to coarsening while balancing computational costs.

Colorectal cancer (CRC) is a global health issue with noticeably high incidence and mortality. Microsimulation models offer a time-efficient method to dynamically analyze multiple screening strategies. The study aimed to identify the efficient organized CRC screening strategies for Shenzhen City.

A microsimulation model named CMOST was employed to simulate CRC screening among 1 million people without migration in Shenzhen, with two CRC developing pathways and real-world participation rates. Initial screening included the National Colorectal Polyp Care score (NCPCS), fecal immunochemical test (FIT), and risk-stratification model (RS model), followed by diagnostic colonoscopy for positive results. Several start-ages (40, 45, 50 years), stop-ages (70, 75, 80 years), and screening intervals (annual, biennial, triennial) were assessed for each strategy. The efficiency of CRC screening was assessed by number of colonoscopies versus life-years gained (LYG).

The screening strategies reduced CRC lifetime incidence by 14-27 cases (30.9-59.0%) and mortality by 7-12 deaths (41.5-71.3%), yielded 83-155 LYG, while requiring 920 to 5901 colonoscopies per 1000 individuals. Out of 81 screening, 23 strategies were estimated efficient. Most of the efficient screening strategies started at age 40 (17 out of 23 strategies) and stopped at age 70 (13 out of 23 strategies). Predominant screening intervals identified were annual for NCPCS, biennial for FIT, and triennial for RS models. The incremental colonoscopies to LYG ratios of efficient screening increased with shorter intervals within the same test category. Compared with no screening, when screening at the same start-to-stop age and interval, the additional colonoscopies per LYG increased progressively for FIT, NCPCS and RS model.

This study identifies efficient CRC screening strategies for the average-risk population in Shenzhen. Most efficient screening strategies indeed start at age 40, but the optimal starting age depends on the chosen willingness-to-pay threshold. Within insufficient colonoscopy resources, efficient FIT and NCPCS screening strategies might be CRC initial screening strategies. We acknowledged the age-dependency bias of the results with NCPCS and RS.

New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers.

A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles.

Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence.

New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.

Fecal Immunochemical Test (FIT) followed by a colonoscopy is an efficacious strategy to improve the adenoma detection rate and Colorectal Cancer (CRC). There is no organized national screening program for CRC in Brazil. The aim of this research was to describe the implementation of an organized screening program for CRC through FIT followed by colonoscopy, in an urban low-income community of São Paulo city. The endpoints of the study were: FIT participation rate, FIT positivity rate, colonoscopy compliance rate, Positive Predictive Values (PPV) for adenoma and CRC, and the rate of complications. From May 2016 to October 2019, asymptomatic individuals, 50-75 years old, received a free kit to perform the FIT. Positive FIT (≥ 50 ng/mL) individuals were referred to colonoscopy. 10,057 individuals returned the stool sample for analysis, of which (98.2%) 9,881 were valid. Women represented 64.8% of the participants. 55.3% of individuals did not complete elementary school. Positive FIT was 7.8% (776/9881). The colonoscopy compliance rate was 68.9% (535/776). There were no major colonoscopy complications. Adenoma were detected in 63.2% (332/525) of individuals. Advanced adenomatous lesions were found in 31.4% (165/525). CRC was diagnosed in 5.9% (31/525), characterized as adenocarcinoma: in situ in 3.2% (1/31), intramucosal in 29% (9/31), and invasive in 67.7% (21/31). Endoscopic treatment with curative intent for CRC was performed in 45.2% (14/31) of the cases. Therefore, in an urban low-income community, an organized CRC screening using FIT followed by colonoscopy ensued a high participation rate, and high predictive positive value for both, adenoma and CRC.

Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South-Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019. The positivity threshold was >15 mcg haemoglobin/g faeces (mcg/g). Due to organizational challenges, the interval between screening rounds randomly varied between 1.5 and 3.5 years, forming a natural experiment. We investigated the detection rate of CRC and advanced neoplasia (AN: CRC or advanced adenoma) at the subsequent round (FIT₂ ), according to the faecal haemoglobin concentration (f-Hb) at the initial screening round (FIT₁ ), and time between the two screening rounds. 18 522 individuals with negative FIT₁ who attended FIT₂ were included in this study. 245 AN were detected at FIT₂ , of which 34 were CRC. The CRC detection rate at FIT₂ for participants with FIT₁  = 0 mcg/g was 0.09% while it was 0.28% for participant with 0 > FIT₁  ≤ 15 mcg/g; odds ratio (OR) 3.22, 95% CI 1.49-6.95. For each 3 months' increment between FITs, the OR for detecting CRC was 1.33 (95% CI 0.98-1.79), while the OR was 1.13 (1.02-1.26) for AN. Individuals with FIT₁ -value of 0 mcg/g, had a lower AN detection rate compared with participants with 0 > FIT₁  ≤ 15 mcg/g, irrespective of time between tests. Although CRC and AN detection rates increase with increasing time interval between FITs, individuals with undetectable f-Hb at first screen have substantially lower risk of CRC at the next screening round compared with individuals with detectable f-Hb.

Patterns of longitudinal adherence may predict advanced neoplasia (AN) detection in subsequent rounds of colorectal cancer (CRC) screening. However, after more than five rounds, it is important to obtain a simplified measure. The aim was to determine the best simplified measure of longitudinal adherence to predict AN detection in CRC screening.

Individuals with four invitations from a Dutch Fecal immunochemical testing (FIT-)based pilot study and two Italian FIT-based CRC screening programs were included. We calculated AN detection in the fourth round, stratified by prior adherence. Five simplified measures were compared to full information (permutations) using chi-squared goodness-of-fit: adherence previous invitation, consistency, frequency, frequency + adherence previous invitation, and proportion of invitations covered.

AN detection in the fourth round was highly dependent on prior adherence behavior. For inconsistent adherence, detection in the fourth round was strongly dependent on frequency and time since last participation. The performance of the simplified measures to capture this variation differed considerably. 'Adherence previous invitation' scored worst in predicting AN detection. 'Frequency+adherence previous invitation' had lowest chi-squared goodness-of-fit.

The simplified measure 'frequency+adherence previous invitation' is the best measure to reflect patterns of longitudinal adherence and could be used to emphasize to individuals the importance of CRC screening.

Screening colonoscopy for early detection and prevention of colorectal cancer (CRC) is mostly used inefficiently. Here, we assessed the potential of an innovative approach to colonoscopy-based screening, by use of a single, low threshold fecal immunochemical test (FIT) as a "gateopener" for screening colonoscopy. Using COSIMO, a validated simulation model, we modeled scenarios including either direct invitation to screening colonoscopy or an alternative approach involving mailing a single ("gateopener") FIT along with an invitation to colonoscopy contingent on a FIT value above a low threshold yielding a 50% positivity rate (ie, every other pretest will be positive). Under plausible assumptions on screening offer adherence, we found that such "gateopener screening" (use of screening colonoscopy contingent on a positive, low threshold gateopener FIT) approximately doubled cancer detection rates vs conventional screening. In those spared from screening colonoscopy due to a negative gateopener FIT pretest, numbers needed to screen were 10-times higher vs those for individuals with a positive FIT, peaking in >2000 and >3800 (hypothetically) needed colonoscopies to detect one case of cancer in men and women, respectively. Gateopener screening resulted in 42%-51% and 59%-65% more prevented CRC cases and deaths, respectively. In summary, by directing colonoscopy capacities to those most likely to benefit, offering screening colonoscopy contingent on a "gateopener" low-threshold FIT would substantially enhance efficiency of colonoscopy screening.

In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is used at a cut-off of 47 µg Hb per gram feces. The CRC screening program successfully started, with high participation rates and yield of screening. Now that the program has reached a steady state, there is potential to further optimize the program. Previous studies showed that prior fecal Hb (f-Hb) concentrations just below the FIT cut-off are associated with a higher risk for detection of advanced neoplasia (AN) at subsequent screening rounds. We aim to achieve a better balance between the harms and benefits of CRC screening by offering participants tailored invitation intervals based on prior f-Hb concentrations after negative FIT.

This mixed-methods study will be performed within the Dutch national CRC screening program and will consist of: (1) a randomized controlled trial (RCT), (2) focus group studies, and (3) decision modelling. The primary outcome is the yield of AN per screened individual in personalized screening vs. uniform screening. Secondary outcomes are perspectives on, acceptability of and adherence to personalized screening, as well as long-term outcomes of personalized vs. uniform screening. The RCT will include 20,000 participants of the Dutch CRC screening program; 10,000 in the intervention and 10,000 in the control arm. The intervention arm will receive a personalized screening interval based on the prior f-Hb concentration (1, 2 or 3 years). The control arm will receive a screening interval according to current practice (2 years). The focus group studies are designed to understand individuals' perspectives on and acceptability of personalized CRC screening. Results of the RCT will be incorporated into the MISCAN-Colon model to determine long-term benefits, harms, and costs of personalized vs. uniform CRC screening.

The aim of this study is to evaluate the yield, feasibility, acceptability and (cost-) effectiveness of personalized CRC screening through tailored invitation intervals based on prior f-Hb concentrations. This knowledge may be of guidance for health policy makers and may provide evidence for implementing personalized CRC screening in The Netherlands and/or other countries using FIT as screening modality.

ClinicalTrials.gov, NCT05423886, June 21, 2022, https://clinicaltrials.gov/ct2/show/NCT05423886.

The NHS Bowel Cancer Screening Programme (BCSP) faces endoscopy capacity challenges from the COVID-19 pandemic and plans to lower the screening starting age. This may necessitate modifying the interscreening interval or threshold.

We analysed data from the English Faecal Immunochemical Testing (FIT) pilot, comprising 27,238 individuals aged 59-75, screened for colorectal cancer (CRC) using FIT. We estimated screening sensitivity to CRC, adenomas, advanced adenomas (AA) and mean sojourn time of each pathology by faecal haemoglobin (f-Hb) thresholds, then predicted the detection of these abnormalities by interscreening interval and f-Hb threshold.

Current 2-yearly screening with a f-Hb threshold of 120 μg/g was estimated to generate 16,092 colonoscopies, prevent 186 CRCs, detect 1142 CRCs, 7086 adenomas and 4259 AAs per 100,000 screened over 15 years. A higher threshold at 180 μg/g would reduce required colonoscopies to 11,500, prevent 131 CRCs, detect 1077 CRCs, 4961 adenomas and 3184 AAs. A longer interscreening interval of 3 years would reduce required colonoscopies to 10,283, prevent 126 and detect 909 CRCs, 4796 adenomas and 2986 AAs.

Increasing the f-Hb threshold was estimated to be more efficient than increasing the interscreening interval regarding overall colonoscopies per screen-benefited cancer. Increasing the interval was more efficient regarding colonoscopies per cancer prevented.

Worldwide, many countries have adopted colorectal cancer (CRC) screening programmes, often based on faecal occult blood tests (FOBTs). CRC screening aims to detect advanced neoplasia (AN), which is defined as CRC or advanced adenomas. FOBTs fall into two categories based on detection technique and the detected blood component: qualitative guaiac-based FOBTs (gFOBTs) and faecal immunochemical tests (FITs), which can be qualitative and quantitative. Screening with gFOBTs reduces CRC-related mortality.

To compare the diagnostic test accuracy of gFOBT and FIT screening for detecting advanced colorectal neoplasia in average-risk individuals.

We searched CENTRAL, MEDLINE, Embase, BIOSIS Citation Index, Science Citation Index Expanded, and Google Scholar. We searched the reference lists and PubMed-related articles of included studies to identify additional studies.

We included prospective and retrospective studies that provided the number of true positives, false positives, false negatives, and true negatives for gFOBTs, FITs, or both, with colonoscopy as reference standard. We excluded case-control studies. We included studies in which all participants underwent both index test and reference standard ("reference standard: all"), and studies in which only participants with a positive index test underwent the reference standard while participants with a negative test were followed for at least one year for development of interval carcinomas ("reference standard: positive"). The target population consisted of asymptomatic, average-risk individuals undergoing CRC screening. The target conditions were CRC and advanced neoplasia (advanced adenomas and CRC combined).

Two review authors independently screened and selected studies for inclusion. In case of disagreement, a third review author made the final decision. We used the Rutter and Gatsonis hierarchical summary receiver operating characteristic model to explore differences between tests and identify potential sources of heterogeneity, and the bivariate hierarchical model to estimate sensitivity and specificity at common thresholds: 10 µg haemoglobin (Hb)/g faeces and 20 µg Hb/g faeces. We performed indirect comparisons of the accuracy of the two tests and direct comparisons when both index tests were evaluated in the same population.

We ran the initial search on 25 June 2019, which yielded 63 studies for inclusion. We ran a top-up search on 14 September 2021, which yielded one potentially eligible study, currently awaiting classification. We included a total of 33 "reference standard: all" published articles involving 104,640 participants. Six studies evaluated only gFOBTs, 23 studies evaluated only FITs, and four studies included both gFOBTs and FITs. The cut-off for positivity of FITs varied between 2.4 μg and 50 µg Hb/g faeces. For each Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 domain, we assessed risk of bias as high in less than 20% of studies. The summary curve showed that FITs had a higher discriminative ability than gFOBTs for AN (P < 0.001) and CRC (P = 0.004). For the detection of AN, the summary sensitivity of gFOBTs was 15% (95% confidence interval (CI) 12% to 20%), which was significantly lower than FITs at both 10 μg and 20 μg Hb/g cut-offs with summary sensitivities of 33% (95% CI 27% to 40%; P < 0.001) and 26% (95% CI 21% to 31%, P = 0.002), respectively. Results were simulated in a hypothetical cohort of 10,000 screening participants with 1% CRC prevalence and 10% AN prevalence. Out of 1000 participants with AN, gFOBTs missed 850, while FITs missed 670 (10 μg Hb/g cut-off) and 740 (20 μg Hb/g cut-off). No significant differences in summary specificity for AN detection were found between gFOBTs (94%; 95% CI 92% to 96%), and FITs at 10 μg Hb/g cut-off (93%; 95% CI 90% to 95%) and at 20 μg Hb/g cut-off (97%; 95% CI 95% to 98%). So, among 9000 participants without AN, 540 were offered (unnecessary) colonoscopy with gFOBTs compared to 630 (10 μg Hb/g) and 270 (20 μg Hb/g) with FITs. Similarly, for the detection of CRC, the summary sensitivity of gFOBTs, 39% (95% CI 25% to 55%), was significantly lower than FITs at 10 μg and 20 μg Hb/g cut-offs: 76% (95% CI 57% to 88%: P = 0.001) and 65% (95% CI 46% to 80%; P = 0.035), respectively. So, out of 100 participants with CRC, gFOBTs missed 61, and FITs missed 24 (10 μg Hb/g) and 35 (20 μg Hb/g). No significant differences in summary specificity for CRC were found between gFOBTs (94%; 95% CI 91% to 96%), and FITs at the 10 μg Hb/g cut-off (94%; 95% CI 87% to 97%) and 20 μg Hb/g cut-off (96%; 95% CI 91% to 98%). So, out of 9900 participants without CRC, 594 were offered (unnecessary) colonoscopy with gFOBTs versus 594 (10 μg Hb/g) and 396 (20 μg Hb/g) with FITs. In five studies that compared FITs and gFOBTs in the same population, FITs showed a higher discriminative ability for AN than gFOBTs (P = 0.003). We included a total of 30 "reference standard: positive" studies involving 3,664,934 participants. Of these, eight were gFOBT-only studies, 18 were FIT-only studies, and four studies combined both gFOBTs and FITs. The cut-off for positivity of FITs varied between 5 µg to 250 µg Hb/g faeces. For each QUADAS-2 domain, we assessed risk of bias as high in less than 20% of studies. The summary curve showed that FITs had a higher discriminative ability for detecting CRC than gFOBTs (P < 0.001). The summary sensitivity for CRC of gFOBTs, 59% (95% CI 55% to 64%), was significantly lower than FITs at the 10 μg Hb/g cut-off, 89% (95% CI 80% to 95%; P < 0.001) and the 20 μg Hb/g cut-off, 89% (95% CI 85% to 92%; P < 0.001). So, in the hypothetical cohort with 100 participants with CRC, gFOBTs missed 41, while FITs missed 11 (10 μg Hb/g) and 11 (20 μg Hb/g). The summary specificity of gFOBTs was 98% (95% CI 98% to 99%), which was higher than FITs at both 10 μg and 20 μg Hb/g cut-offs: 94% (95% CI 92% to 95%; P < 0.001) and 95% (95% CI 94% to 96%; P < 0.001), respectively. So, out of 9900 participants without CRC, 198 were offered (unnecessary) colonoscopy with gFOBTs compared to 594 (10 μg Hb/g) and 495 (20 μg Hb/g) with FITs. At a specificity of 90% and 95%, FITs had a higher sensitivity than gFOBTs.

FITs are superior to gFOBTs in detecting AN and CRC in average-risk individuals. Specificity of both tests was similar in "reference standard: all" studies, whereas specificity was significantly higher for gFOBTs than FITs in "reference standard: positive" studies. However, at pre-specified specificities, the sensitivity of FITs was significantly higher than gFOBTs.

In 2016, it was announced that the fecal immunochemical test (FIT) would replace the guaiac fecal occult blood test in the UK Bowel Cancer Screening Programme. England has limited endoscopy capacity. This study informed decision making by determining the most cost-effective FIT screening strategy (age range, frequency, and FIT threshold) under a constrained endoscopy capacity.

An economic model with a colorectal cancer natural history component was used to model 60 221 screening strategies with first screening at age 50 to 60 years, screening interval of 1 to 6 years, 3+ screening episodes, and FIT integer threshold of 20 to 180 μg hemoglobin/g feces. Screening strategies requiring the same endoscopy capacity were compared to determine the characteristics of the most cost-effective strategies.

With 50 000 annual screening referral colonoscopies, the 20 most cost-effective strategies had a starting age of 50 to 53 years, 2-yearly screening, 7 or 8 rounds of screening, and FIT threshold of 127 to 166. Compared with a 2-yearly screening interval, screening less frequently (3-, 4-, 5-, or 6-yearly) with a more sensitive FIT was less cost-effective.

The UK Bowel Cancer Screening Programme should use a 2-yearly FIT screening interval. When endoscopy capacity increases, the screening starting age should be reduced first followed by reducing the FIT threshold. These findings are relevant for other colorectal cancer screening programs with constrained endoscopy capacity.

Reports of mailed fecal immunochemical test (FIT) outreach effectiveness over time are minimal. We aimed to better evaluate a mailed FIT program with longitudinal metrics.

A total of 10,771 patients aged 50 to 75 years not up-to-date with colorectal cancer screening were randomized to intervention or usual care. The intervention arm received an advanced notification call and informational postcard prior to a mailed FIT. Usual care was at the discretion of the primary care provider. Patients were followed for up to 2.5 years. The primary outcome was the difference in cumulative proportion of completed FIT screening between arms. Screening was further examined with the proportion of time up-to-date, consistency of adherence, and frequency of abnormal FIT.

The cumulative proportion of FIT completion was higher in the outreach intervention (73.2% vs 55.1%; P < .001). The proportion of time covered by screening was higher in the intervention group (46.8% vs 27.3%; Δ19.6%; 95% confidence interval, 18.2%-20.9%). Patients assigned to FIT outreach were more likely to consistently complete FITs (2 completed of 2 offered) (50.1% vs 21.8%; P < .001). However, for patients who did not complete the FIT during the first cycle, only 17.1% completed a FIT during the second outreach cycle. The number and overall proportion of abnormal FIT was significantly higher in the outreach intervention (6.9% Outreach vs 4.1% Usual Care; P < .01).

Organized mailed FIT outreach significantly increased colorectal cancer screening over multiple years in this safety-net health system. Although mailing was overall effective, the effect was modest in patients who did not complete FIT in first cycle of intervention. (ClincialTrials.gov, NCT02613260).

Roll-out of population-based colorectal cancer (CRC) screening with faecal immunochemical test (FIT) is limited by availability of further investigations, particularly colonoscopy and examination of excised lesions. Our objective was to assess whether variation in number of faecal samples and threshold adjustment can optimise resource utilisation and CRC detection rate.

Three different screening strategies were compared for the same FIT threshold using a quantitative FIT system: one FIT, positive when >20 µg Hb/g faeces; two FIT, positive when either was >20 µg Hb/g faeces; and two FIT, positive when the mean was >20 µg Hb/g faeces. We calculated changes in the size of population the provider could invite to screening for an equal number of screening positive results, and CRC and adenoma detected.

In our setting, Region of Murcia, south of Spain (not fully rolled out screening programme), changing the usual strategy of two FIT, positive when either to positive when the mean was >20 µg Hb/g faeces, would increase population invited by 37.81% with the same number of positive results (which would generate a CRC detection rate of 19.2%). In a fully rolled out programme, changing the strategy from one to two FIT (positive when the mean is >20 µg Hb/g faeces), would increase CRC detection rate by 4.64% with an increase of only 13.34% in positive FIT.

In a population-based CRC screening programme, smart use of number of FITs and positivity threshold can increase population invited and CRC detection without increasing the number of colonoscopies and pathological examinations needed.

The National Health Service Bowel Cancer Screening Programme (NHS BCSP) in England has replaced guaiac faecal occult blood testing by faecal immunochemical testing (FIT). There is interest in fully exploiting FIT measures to improve bowel cancer (CRC) screening strategies. In this paper, we estimate the relationship of the quantitative haemoglobin concentration provided by FIT in faecal samples with underlying pathology. From this we estimate thresholds required for given levels of sensitivity to CRC and high-risk adenomas (HRA).

Data were collected from a pilot study of FIT in England in 2014, in which 27,238 participants completed a FIT. Those with a faecal haemoglobin concentration (f-Hb) of at least 20 µg/g were referred for further investigation, usually colonoscopy. Truncated regression models were used to explore the relationship between bowel pathology and FIT results. Regression results were applied to estimate sensitivity to different abnormalities for a number of thresholds.

Participants with CRC and HRA had significantly higher f-Hb, and this remained unchanged after adjusting for age and sex. While a threshold of 20 μg/g was estimated to capture 82.2% of CRC and 64.0% of HRA, this would refer 7.8% of participants for colonoscopy. The current programme threshold used in England of 120 μg/g was estimated to identify 47.8% of CRC and 25.0% of HRA.

Under the current diagnostic policy of dichotomising FIT results, a very low threshold would be required to achieve high sensitivity to CRC and HRA, which would place further strain on colonoscopy resources. The NHS BCSP in England might benefit from a diagnostic policy that makes greater use of the quantitative nature of FIT.

Screening for colorectal cancer (CRC) can effectively reduce CRC incidence and mortality. Besides colonoscopy, tests for the detection of biomarkers in stool, blood, or serum, including the fecal immunochemical test (FIT), ColoGuard, Epi proColon, and PolypDx, have recently been advanced. We aimed to identify the characteristics of theoretic, highly efficient screening tests and calculated the effectiveness and cost effectiveness of available screening tests.

Using the microsimulation-based colon modeling open-source tool (CMOST), we simulated 142,501 theoretic screening tests with variable assumptions for adenoma and carcinoma sensitivity, specificity, test frequency, and adherence, and we identified highly efficient tests outperforming colonoscopy. For available screening tests, we simulated 10 replicates of a virtual population of 2 million individuals, using epidemiologic characteristics and costs assumptions of the United States.

Highly efficient theoretic screening tests were characterized by high sensitivity for advanced adenoma and carcinoma and high patient adherence. All simulated available screening tests were effective at 100% adherence to screening and at expected real-world adherence rates. All tests were cost effective below the threshold of 100,000 U.S. dollars per life year gained. With perfect adherence, FIT was the most effective and cost-efficient intervention, whereas Epi proColon was the most effective at expected real-world adherence rates. In our sensitivity analysis, assumptions for patient adherence had the strongest impact on effectiveness of screening.

Our microsimulation study identified characteristics of highly efficient theoretic screening tests and confirmed the effectiveness and cost-effectiveness of colonoscopy and available urine-, blood-, and stool-based tests. Better patient adherence results in superior effectiveness for CRC prevention in the whole population.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in the worldwide. Colonoscopy is the gold standard for screening and surveillance of CRC. Removing adenomas by colonoscopy has lowered the incidence and mortality of CRC. However, colonoscopy is imperfect for detection of colorectal neoplasia. After a colonoscopy that is negative for malignancy, CRC can be diagnosed. These are termed as post-colonoscopy CRC (PCCRC). The proportion of PCCRC, among all CRC was reported to be 1.8% to 9.0%. It occurred 2.4 times more in the right colon than in the left colon. The causes of PCCRC are missed lesions, incomplete resection, and new lesions. Among these causes, missed lesion and incomplete resection are procedural factors and preventable. Therefore, it is necessary to improve the quality of colonoscopy to minimize the occurrence of PCCRC.

Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the US.

To systematically review the effectiveness, test accuracy, and harms of screening for CRC to inform the US Preventive Services Task Force.

MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2015, to December 4, 2019; surveillance through March 26, 2021.

English-language studies conducted in asymptomatic populations at general risk of CRC.

Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted.

Colorectal cancer incidence and mortality, test accuracy in detecting cancers or adenomas, and serious adverse events.

The review included 33 studies (n = 10 776 276) on the effectiveness of screening, 59 (n = 3 491 045) on the test performance of screening tests, and 131 (n = 26 987 366) on the harms of screening. In randomized clinical trials (4 trials, n = 458 002), intention to screen with 1- or 2-time flexible sigmoidoscopy vs no screening was associated with a decrease in CRC-specific mortality (incidence rate ratio, 0.74 [95% CI, 0.68-0.80]). Annual or biennial guaiac fecal occult blood test (gFOBT) vs no screening (5 trials, n = 419 966) was associated with a reduction of CRC-specific mortality after 2 to 9 rounds of screening (relative risk at 19.5 years, 0.91 [95% CI, 0.84-0.98]; relative risk at 30 years, 0.78 [95% CI, 0.65-0.93]). In observational studies, receipt of screening colonoscopy (2 studies, n = 436 927) or fecal immunochemical test (FIT) (1 study, n = 5.4 million) vs no screening was associated with lower risk of CRC incidence or mortality. Nine studies (n = 6497) evaluated the test accuracy of screening computed tomography (CT) colonography, 4 of which also reported the test accuracy of colonoscopy; pooled sensitivity to detect adenomas 6 mm or larger was similar between CT colonography with bowel prep (0.86) and colonoscopy (0.89). In pooled values, commonly evaluated FITs (14 studies, n = 45 403) (sensitivity, 0.74; specificity, 0.94) and stool DNA with FIT (4 studies, n = 12 424) (sensitivity, 0.93; specificity, 0.85) performed better than high-sensitivity gFOBT (2 studies, n = 3503) (sensitivity, 0.50-0.75; specificity, 0.96-0.98) to detect cancers. Serious harms of screening colonoscopy included perforations (3.1/10 000 procedures) and major bleeding (14.6/10 000 procedures). CT colonography may have harms resulting from low-dose ionizing radiation. It is unclear if detection of extracolonic findings on CT colonography is a net benefit or harm.

There are several options to screen for colorectal cancer, each with a different level of evidence demonstrating its ability to reduce cancer mortality, its ability to detect cancer or precursor lesions, and its risk of harms.

We aimed to report the results of the implementation of the National Colorectal Cancer (CRC) Screening Program covering all the country. The National Health Insurance Fund (NHIF) reimburses the institutions for performing each service; each procedure within the program has its own administrative code. Information about services provided within the program was retrieved from the database of NHIF starting from the 1 January 2014 to the 31 December 2018. Exact date and type of all provided services, test results, date and results of biopsy and histopathological examination were extracted together with the vital status at the end of follow-up, date of death and date of emigration when applicable for all men and women born between 1935 and 1968. Results were compared with the guidelines of the European Union for quality assurance in CRC screening and diagnosis. The screening uptake was 49.5% (754,061 patients) during study period. Participation rate varied from 16% to 18.1% per year and was higher among women than among men. Proportion of test-positive and test-negative results was similar during all the study period-8.7% and 91.3% annually. Between 9.2% and 13.5% of test-positive patients received a biopsy of which 52.3-61.8% were positive for colorectal adenoma and 4.6-7.3% for colorectal carcinoma. CRC detection rate among test-positive individuals varied between 0.93% and 1.28%. The colorectal cancer screening program in Lithuania coverage must be improved. A screening database is needed to systematically evaluate the impact and performance of the national CRC screening program and quality assurance within the program.

Colorectal cancer (CRC) is the third most common cancer in men and women in the United States. CRC screening efforts are directed toward removal of adenomas and sessile serrated lesions and detection of early-stage CRC. The purpose of this article is to update the 2009 American College of Gastroenterology CRC screening guidelines. The guideline is framed around several key questions. We conducted a comprehensive literature search to include studies through October 2020. The inclusion criteria were studies of any design with men and women age 40 years and older. Detailed recommendations for CRC screening in average-risk individuals and those with a family history of CRC are discussed. We also provide recommendations on the role of aspirin for chemoprevention, quality indicators for colonoscopy, approaches to organized CRC screening and improving adherence to CRC screening. CRC screening must be optimized to allow effective and sustained reduction of CRC incidence and mortality. This can be accomplished by achieving high rates of adherence, quality monitoring and improvement, following evidence-based guidelines, and removing barriers through the spectrum of care from noninvasive screening tests to screening and diagnostic colonoscopy. The development of cost-effective, highly accurate, noninvasive modalities associated with improved overall adherence to the screening process is also a desirable goal.

To examine the impact of increasing multi-target stool DNA test (mt-sDNA [Cologuard]) utilization for colorectal cancer (CRC) screening in cohorts aged 50-75 and 45-75 years old with varying levels of adherence from the perspectives of integrated delivery networks (IDNs) and payers.

We developed a budget impact model that simulates CRC screening with colonoscopy over a 10-year time horizon, fecal immunochemical test (FIT), and mt-sDNA according to the United States Preventive Services Task Force and American Cancer Society guidelines for average risk adults. We evaluated varying levels of screening adherence for a status quo scenario and for an increased mt-sDNA utilization scenario, from the IDN and payer perspectives. The IDN perspective included CRC screening program costs, whereas the payer perspective did not. Conversely, stool-based screening test and bowel preparation costs were unique to the payer perspective.

The increased mt-sDNA scenarios yielded cost savings relative to the status quo under all adherence scenarios due to a decrease in screening and surveillance colonoscopies. For ages 50-75, in high and low adherence scenarios, savings were $19.8 M ($0.16 per-person-per-month (PPPM)) and $33.3 M ($0.28 PPPM) from the IDN perspective. From the payer perspective, savings were $4.2 M ($0.03 PPPM) and $6.7 M ($0.06 PPPM). For ages 45-75, in high and low adherence scenarios, cost savings were $19.3 M ($0.16 PPPM) and $33.0 M ($0.28 PPPM) from the IDN perspective and $3.9 M ($0.03 PPPM) and $6.2 M ($0.05 PPPM) from the payer perspective. In all imperfect adherence scenarios, the degree of cost-savings with increased mt-sDNA utilization correlated with the aggregate decrease in screening and surveillance colonoscopies.

Estimates of real-world adherence levels were based on cross-sectional screening data from the literature, and assumptions were applied to individual screening modalities and screening scenarios.

Among all adherence scenarios, perspectives, and age ranges, increased mt-sDNA utilization yielded cost-savings.

Real-world adherence to colorectal cancer (CRC) screening strategies is imperfect. The CRC-AIM microsimulation model was used to estimate the impact of imperfect adherence on the relative benefits and burdens of guideline-endorsed, stool-based screening strategies.

Predicted outcomes of multi-target stool DNA (mt-sDNA), fecal immunochemical tests (FIT), and high-sensitivity guaiac-based fecal occult blood tests (HSgFOBT) were simulated for 40-year-olds free of diagnosed CRC. For robustness, imperfect adherence was incorporated in multiple ways and with extensive sensitivity analysis. Analysis 1 assumed adherence from 0%-100%, in 10% increments. Analysis 2 longitudinally applied real-world first-round differential adherence rates (base-case imperfect rates = 40% annual FIT vs 34% annual HSgFOBT vs 70% triennial mt-sDNA). Analysis 3 randomly assigned individuals to receive 1, 5, or 9 lifetime (9 = 100% adherence) mt-sDNA tests and 1, 5, or 9 to 26 (26 = 100% adherence) FIT tests. Outcomes are reported per 1000 individuals compared with no screening.

Each screening strategy decreased CRC incidence and mortality versus no screening. In individuals screened between ages 50-75 and adherence ranging from 10%a-100%, the life-years gained (LYG) for triennial mt-sDNA ranged from 133.1-300.0, for annual FIT from 96.3-318.1, and for annual HSgFOBT from 99.8-320.6. At base-case imperfect adherence rates, mt-sDNA resulted in 19.1% more LYG versus FIT, 25.4% more LYG versus HSgFOBT, and generally had preferable efficiency ratios while offering the most LYG. Completion of at least 21 FIT tests is needed to reach approximately the same LYG achieved with 9 mt-sDNA tests.

Adherence assumptions affect the conclusions of CRC screening microsimulations that are used to inform CRC screening guidelines. LYG from FIT and HSgFOBT are more sensitive to changes in adherence assumptions than mt-sDNA because they require more tests be completed for equivalent benefit. At imperfect adherence rates, mt-sDNA provides more LYG than FIT or HSgFOBT at an acceptable tradeoff in screening burden.

The fecal immunochemical test (FIT) is a cost-effective colorectal cancer (CRC) screening tool. However, longitudinal adherence, a factor that is critical to the success to any FIT-based screening program, often is poor. The authors hypothesized that reminders sent via mobile messengers, such as WhatsApp, improve such adherence.

In the current single-blind, randomized study, subjects from an opportunistic FIT screening program who had a negative FIT result the year prior were randomly allocated (1:1) to receive either a 1-off reminder via the WhatsApp messenger (WR) 1 month prior to the due appointments or no reminder (NR). All subjects were blinded to study participation and group allocation. At 24 months after randomization, a crossover of intervention was performed among those individuals who remained in the FIT program. The primary outcome was FIT adherence, defined as the pick-up and on-time return of the FIT. The secondary outcome was FIT adherence after the crossover.

A total of 500 subjects were randomized to receive WR (250 subjects) or NR (250 subjects). Three individuals were excluded from analysis (1 died and 2 underwent colonoscopy). Both the FIT pick-up rate (80.3% vs 59.3%; P < .001) and return rate (79.9% vs 57.3%; P < .001) were significantly higher in the WR group compared with the NR group. After crossover of intervention (452 subjects), the WR group again was found to have a higher FIT pick-up rate (79.1% vs 52.9%; P < .001) and return rate (78.2% vs 52.4%; P < .001).

Text reminders sent via mobile messenger appear to improve the longitudinal adherence to FIT-based opportunistic CRC screening programs. The routine use of this technology in CRC screening should be considered.

Most screening in the United States occurs in an opportunistic fashion, although organized screening occurs in some integrated health care systems. Organized colorectal cancer (CRC) screening consists of an explicit screening policy, defined target population, implementation team, health care team for clinical care delivery, quality assurance infrastructure, and method for identifying cancer outcomes. Implementation of an organized screening program offers opportunities to systematically assess the success of the program and develop interventions to address identified gaps in an effort to optimize CRC outcomes. There is evidence of that organized screening is associated with improvements in screening participation and CRC mortality.

The current organized screening program for colorectal cancer in Germany offers both sexes 5 annual fecal immunochemical tests (FITs) between ages 50 and 54 years, followed by a first screening colonoscopy at age 55 years if all of these FITs were negative. We sought to assess the implications of this approach for key parameters of diagnostic performance.

Using a multistate Markov model, we estimated the expected detection rates of advanced neoplasms (advanced adenomas and cancers) and number needed to scope (NNS) to detect 1 advanced neoplasm at a first screening colonoscopy conducted at age 55 after 5 preceding negative FITs and compared them with the corresponding estimates for a first screening colonoscopy at age 55 with no preceding FIT testing. In individuals with 5 consecutive negative FITs undergoing screening colonoscopy at age 55, expected colonoscopy detection rate (NNS) was 3.7% (27) and 0.10% (1,021) for any advanced neoplasm and cancer, respectively, in men, and 2.1% (47) and 0.05% (1,880) for any advanced neoplasm and cancer, respectively, in women. These NNS values for detecting 1 advanced neoplasm are approximately 3-fold higher, and the NNS values for detecting 1 cancer are approximately 8-fold higher, than those for a first screening colonoscopy at age 55 without prior FITs. This study is limited by model simplifying assumptions and uncertainties related to input parameters.

Screening colonoscopy at age 55 after 5 consecutive negative FITs at ages 50-54, as currently offered in the German cancer early detection program, is expected to have very low positive predictive value. Our results may inform efforts to enhance the design of screening programs.

Aims: To evaluate total costs and health consequences of a colorectal cancer (CRC) screening program with colonoscopy, fecal immunochemical tests (FIT), and expanded use of multitarget stool DNA (mt-sDNA) from the perspectives of Integrated Delivery Networks (IDNs) and payers in the United States.Materials and methods: We developed a budget impact and cost-consequence model that simulates CRC screening for eligible 50- to 75-year-old adults. A status quo scenario and an increased mt-sDNA scenario were modeled. The status quo includes the current screening mix of colonoscopy (83%), FIT (11%), and mt-sDNA (6%) modalities. The increased mt-sDNA scenario increases mt-sDNA utilization to 28% over 10 years. Costs for both the IDN and the payer perspectives incorporated diagnostic and surveillance colonoscopies, adverse events (AEs), and CRC treatment. The IDN perspective included screening program costs, composed of direct nonmedical (e.g. patient navigation) and indirect (e.g. administration) costs. It was assumed that IDNs do not incur the costs for stool-based screening tests or bowel preparation for colonoscopies.Results: In a population of one million covered lives, the 10-year incremental cost savings incurred by increasing mt-sDNA utilization was $16.2 M for the IDN and $3.3 M for the payer. The incremental savings per-person-per-month were $0.14 and $0.03 for the IDN and payer, respectively. For both perspectives, increased diagnostic colonoscopy costs were offset by reductions in screening colonoscopies, surveillance colonoscopies, and AEs. Extending screening eligibility to 45- to 75-year-olds slightly decreased the overall cost savings.Limitations: The natural history of CRC was not simulated; however, many of the utilized parameters were extracted from highly vetted natural history models or published literature. Direct nonmedical and indirect costs for CRC screening programs are applied on a per-person-per modality basis, whereas in reality some of these costs may be fixed.Conclusions: Increased mt-sDNA utilization leads to fewer colonoscopies, less AEs, and lower overall costs for both IDNs and payers, reducing overall screening program costs and increasing the number of cancers detected while maintaining screening adherence rates over 10 years.

Faecal occult blood testing is widely used in colorectal cancer screening. However, there is little empirical long-term evidence on the accumulation of false-positive test results over several screening rounds. We aimed to systematically explore and quantify the cumulative false-positive rate for various scenarios of colorectal cancer screening.

Using a Markov analysis, we estimated the lifetime cumulative number of false-positive test results (cumFP) per 100 000 50-year-old persons. We varied the screening interval and the specificity of a single screening test and the starting age of screening.

For a test with a specificity of 98% used from 50 to 74 years, the cumFP at age 74 was 26 260 (1-year interval), 15 102 (2-year interval), and 10 819 (3-year interval), respectively. For a test with a specificity of, respectively, 95 and 92% used at a 2-year interval, the cumFP at age 74 was 2.2 times and 3.0 times higher as compared to a test with a specificity of 98%. The cumFP at age 74 was 18% lower for screening persons aged 54-74 years vs. 50-74 years.

Our findings quantitatively illustrate the large variation of the cumFP in colorectal cancer screening between screening strategies, which is relevant to informed decision making and adequate resource planning.

The fecal immunochemical test (FIT) and colonoscopy are the most commonly used strategies for colorectal cancer (CRC) screening worldwide. We aimed to compare their efficacy and cost-effectiveness in CRC screening in an average-risk population.

PubMed, Embase, and National Health Services Economic Evaluation Database were searched. Risk ratio (RR) was used to evaluate the differences in detection rates of colorectal neoplasia between FIT and colonoscopy groups. A random-effects model was used to pool RRs. Incremental cost-effectiveness ratios (ICERs) were calculated to evaluate the cost-effectiveness of FIT versus colonoscopy.

Six randomized controlled trials and 17 cost-effectiveness studies were included. The participation rate in the FIT group was higher than that in the colonoscopy group (41.6% vs 21.9%). In the intention-to-treat analysis, FIT had a detection rate of CRC comparable with colonoscopy (RR, .73; 95% confidence interval, .37-1.42) and lower detection rates of any adenoma and advanced adenoma than 1-time colonoscopy. Most included cost-effectiveness studies showed that annual (13/15) or biennial (5/6) FIT was cost-saving (ICER < $0) or very cost-effective ($0 < ICER ≤ $25000/quality-adjusted life-year) compared with colonoscopy every 10 years.

FIT may be similar to 1-time colonoscopy in the detection rate of CRC, although it has lower detection rates of any adenoma and advanced adenoma than 1-time colonoscopy. Furthermore, annual or biennial FIT appears to be very cost-effective or cost-saving compared with colonoscopy every 10 years. These findings indicate, at least partly, that FIT is noninferior to colonoscopy in CRC screening in an average-risk population. Our findings should be treated with caution and need to be further confirmed.

Hodgkin lymphoma (HL) survivors have an increased colorectal cancer (CRC) risk. Diagnostic accuracy of quantitative fecal immunochemical testing (FIT, OC Sensor) and/or a multi-target stool DNA test (mt-sDNA, Cologuard^®) for advanced neoplasia (AN) was evaluated.

101 HL survivors underwent a surveillance colonoscopy and were asked to perform two stool tests (FIT and mt-sDNA). Advanced adenoma (AA), advanced serrated lesion (ASL), and AN (AA, ASL, CRC) were evaluated. Sensitivity, specificity, and area under the curve (AUC) for AN were calculated for different FIT cut-offs and mt-sDNA with colonoscopy as reference.

FIT and mt-sDNA were analyzed in 73 (72%) and 82 (81%) participants, respectively. AN was detected in 19 (26%) and 22 (27%), respectively. AN sensitivities for FIT cut-off of 10 ug Hb/g feces (FIT10) and mt-sDNA were 37% (95% confidence interval (CI): 16-62) and 68% (95% CI: 45-86), with corresponding specificities of 91% (95% CI: 80-97) and 70% (95% CI: 57-86), respectively. AUC for FIT was 0.68 (95% CI: 0.54-0.82) and for mt-sDNA 0.76 (95% CI: 0.63-0.89).

In HL survivors, mt-sDNA showed highest sensitivity but with relatively low specificity for AN. Cost-effectiveness analyses is necessary to determine the optimal surveillance strategy.

Screening, followed by colonoscopic polypectomy (or surgery for malignant lesions), prevents incident colorectal cancer and mortality. However, there are variations in effective application of nearly every aspect of the screening process. Screening is a multistep process, and failure in any single step could result in unnecessary morbidity and mortality. Awareness of variations in operator- and system-dependent performance has led to detailed, comprehensive recommendations in the United States and Europe on how colonoscopy screening should be performed and measured. Likewise, guidance has been provided on quality assurance for nonprimary colonoscopy-based screening programs, including strategies to maximize adherence. Quality improvement is now a validated science, and there is clear evidence that higher quality prevents incident cancer and cancer death. Quality must be addressed at the levels of the system, provider, and individuals, to maximize the benefits of screening for any population. We review the important aspects of measuring and improving the quality of colorectal cancer screening.

Despite the success of provincial screening programs, colorectal cancer (CRC) is still the third most common cancer in Canada and the second most common cause of cancer-related death. Fecal-based tests, such as fecal occult blood test (FOBT) and fecal immunochemical test (FIT), form the foundation of the provincial CRC screening programs in Canada. However, those tests have low sensitivity for CRC precursors, adenomatous polyps and have low adherence. This study evaluated the effectiveness and cost-effectiveness of a new urine metabolomic-based test (UMT) that detects adenomatous polyps and CRC.

A Markov model was designed using data from the literature and provincial healthcare databases for Canadian at average risk for CRC; calibration was performed against statistics data. Screening strategies included the following: FOBT every year, FIT every year, colonoscopy every 10 years, and UMT every year. The costs, quality adjusted life years (QALY) gained, and incremental cost-effectiveness ratios (ICERs) for each strategy were estimated and compared.

Compared with no screening, a UMT strategy reduced CRC mortality by 49.9% and gained 0.15 life years per person at $42,325/life year gained in the base case analysis. FOBT reduced CRC mortality by 14.9% and gained 0.04 life years per person at $25,011/life year gained. FIT reduced CRC mortality by 35.8% and gained 0.11 life years per person at $25,500/life year while colonoscopy reduced CRC mortality by 24.7% and gained 0.08 life years per person at $50,875/life year.

A UMT strategy might be a cost-effective strategy when used in programmatic CRC screening programs.

To estimate benefits and harms of different colorectal cancer screening strategies, stratified by (baseline) 15-year colorectal cancer risk.

Microsimulation modelling study using MIcrosimulation SCreening ANalysis-Colon (MISCAN-Colon).

A parallel guideline committee (BMJ Rapid Recommendations) defined the time frame and screening interventions, including selection of outcome measures.

Norwegian men and women aged 50-79 years with varying 15-year colorectal cancer risk (1-7%).

Four screening strategies were compared with no screening: biennial or annual faecal immunochemical test (FIT) or single sigmoidoscopy or colonoscopy at 100% adherence.

Colorectal cancer mortality and incidence, burdens, and harms over 15 years of follow-up. The certainty of the evidence was assessed using the GRADE approach.

Over 15 years of follow-up, screening individuals aged 50-79 at 3% risk of colorectal cancer with annual FIT or single colonoscopy reduced colorectal cancer mortality by 6 per 1000 individuals. Single sigmoidoscopy and biennial FIT reduced it by 5 per 1000 individuals. Colonoscopy, sigmoidoscopy, and annual FIT reduced colorectal cancer incidence by 10, 8, and 4 per 1000 individuals, respectively. The estimated incidence reduction for biennial FIT was 1 per 1000 individuals. Serious harms were estimated to be between 3 per 1000 (biennial FIT) and 5 per 1000 individuals (colonoscopy); harms increased with older age. The absolute benefits of screening increased with increasing colorectal cancer risk, while harms were less affected by baseline risk. Results were sensitive to the setting defined by the guideline panel. Because of uncertainty associated with modelling assumptions, we applied a GRADE rating of low certainty evidence to all estimates.

Over a 15 year period, all screening strategies may reduce colorectal cancer mortality to a similar extent. Colonoscopy and sigmoidoscopy may also reduce colorectal cancer incidence, while FIT shows a smaller incidence reduction. Harms are rare and of similar magnitude for all screening strategies.

Population-based screening programs are credited with earlier colorectal cancer diagnoses and treatment initiation, which reduce mortality rates and improve patient health outcomes. However, recommended screening methods are unsatisfactory as they are invasive, are resource intensive, suffer from low uptake, or have poor diagnostic performance. Our goal was to identify a urine metabolomic-based biomarker panel for the detection of colorectal cancer that has the potential for global population-based screening.

Prospective urine samples were collected from study participants. Based upon colonoscopy and histopathology results, 342 participants (colorectal cancer, 171; healthy controls, 171) from two study sites (Canada, United States) were included in the analyses. Targeted liquid chromatography-mass spectrometry (LC-MS) was performed to quantify 140 highly valuable metabolites in each urine sample. Potential biomarkers for colorectal cancer were identified by comparing the metabolomic profiles from colorectal cancer versus controls. Multiple models were constructed leading to a good separation of colorectal cancer from controls.

A panel of 17 metabolites was identified as possible biomarkers for colorectal cancer. Using only two of the selected metabolites, namely diacetylspermine and kynurenine, a predictor for detecting colorectal cancer was developed with an AUC of 0.864, a specificity of 80.0%, and a sensitivity of 80.0%.

We present a potentially "universal" metabolomic biomarker panel for colorectal cancer independent of cohort clinical features based on a North American population. Further research is needed to confirm the utility of the profile in a prospective, population-based colorectal cancer screening trial.

A urinary metabolomic biomarker panel was identified for colorectal cancer with the potential of clinical application.

Faecal immunochemical test (FIT)-based colorectal cancer screening requires successive rounds for maximum preventive effect. Advanced neoplasia can bleed intermittently and thus might be missed by single faecal sampling. Few studies have been done on two sample FIT (2-FIT) screening over multiple rounds. Therefore, we compared multiple rounds of one sample FIT (1-FIT) with 2-FIT screening with respect to participation, positive predictive value (PPV), diagnostic yield, and interval colorectal cancer.

In this population-based study, a random selection of asymptomatic individuals aged 50-74 years in the Rotterdam-Rijnmond region, Netherlands, were invited by post for four rounds (every 2 years) of 1-FIT or 2-FIT screening. Key exclusion criteria were a history or colorectal cancer or inflammatory bowel disease, colon imaging in the previous 2 years, and life expectancy of less than 5 years. Per round, invitees received one or two FITs to sample either one or two consecutive bowel movements. OC-Sensor Micro (Eiken Chemical Co., Ltd, Japan) FITs were used by all participants, except the fourth round of screening for the 1-FIT cohort, for which participants used either an OC-Sensor or a FOB-Gold (Sentinel Diagnostics, Milan, Italy). A faecal haemoglobin cutoff concentration of 10 μg/g of faeces in at least one test was used for referral for colonoscopy.

Between 2006 and 2015, of 10 008 invited individuals for the 1-FIT cohort, 9787 were eligible for inclusion, of whom 7310 participated at least once in four successive rounds. Of 3197 invited individuals for the 2-FIT cohort, 3131 were eligible for inclusion, and 2269 participated at least once in four successive rounds. In the 1-FIT screening cohort, 74·7% (7310 of 9787) of invitees participated at least once versus 72·5% (2269 of 3131) of invitees in the 2-FIT cohort (p=0·013). Among participants who participated at least once, the cumulative positivity rate over four rounds was 19·2% (1407 of 7310) for the 1-FIT cohort versus 28·5% (647 of 2269) for the 2-FIT cohort (p<0·0001). The cumulative PPV for advanced neoplasia was 33·0% (432 of 1308 colonoscopies) for the 1-FIT cohort versus 24·2% (147 of 607 colonoscopies) for the 2-FIT cohort (p<0·0001). The cumulative diagnostic yield of advanced neoplasia among invited individuals was 4·4% (432 of 9787) for 1-FIT versus 4·7% (147 of 3131) for 2-FIT screening (p=0·46)). FIT interval colorectal cancers were detected in eight (0·1%) of 7310 participants in the 1-FIT cohort and two (0·1%) of 2269 with 2-FIT screening (p=1·00).

Four rounds of 2-FIT screening with a low faecal haemoglobin cutoff level did not result in a significant increase in diagnostic yield or a decrease in interval colorectal cancers compared with 1-FIT, despite higher colonoscopy demand. Therefore, 1-FIT colorectal cancer screening programmes should be preferred.

None.