Assessment of BRAF V600E (VE1) immunochemistry for the detection of BRAF V600E mutation in non-small cell lung carcinoma cytology specimens.

BACKGROUND: Non-small cell lung carcinoma (NSCLC) patients with BRAF V600E-mutated tumors respond to targeted therapy. Testing for BRAF V600E is commonly performed with molecular methods; however, a mutation-specific VE1 antibody clone can provide an alternative testing option using immunohistochemistry (IHC) for practices using single-gene testing and in situations when the specimen is inadequate for molecular testing. This study evaluates the usefulness of VE1 IHC in screening for BRAF V600E mutations in NSCLC cytology specimens. METHODS: The authors retrospectively identified cytology cases with a diagnosis of NSCLC that had BRAF V600E IHC performed on cell block sections with the monoclonal VE1 antibody clone. The BRAF V600E IHC results were compared with those of molecular testing performed with an amplicon-based next-generation sequencing assay. RESULTS: There were 201 NSCLC cases evaluated. The VE1 IHC was positive in seven of seven BRAF V600E-mutated tumors (100%) and was negative in 158 of 158 nonmutated BRAF V600E tumors (100%). Thirty cases did not undergo molecular testing, primarily because of insufficient tissue or because molecular testing was performed on an alternative specimen. Six cases showed equivocal weak/focal staining: Two cases demonstrated BRAF V600E mutations, and four cases were negative by molecular testing. CONCLUSIONS: This study suggests that BRAF V600E IHC can be used reliably to screen NSCLC cytology specimens, and negative results strongly indicate the absence of a BRAF V600E mutation. Having a low threshold for equivocal staining is recommended with molecular confirmation of BRAF V600E for any cases demonstrating weak and/or focal cytoplasmic staining.

Socioeconomic differences in participation and diagnostic yield within the Dutch national colorectal cancer screening programme with faecal immunochemical testing.

BACKGROUND: CRC mortality rates are higher for individuals with a lower socioeconomic status (SES). Screening could influence health inequalities. We therefore aimed to investigate SES differences in participation and diagnostic yield of FIT screening. METHODS: All invitees in 2014 and 2015 in the Dutch national CRC screening programme were included in the analyses. We used area SES as a measure for SES and divided invitees into quintiles, with Quintile 1 being the highest SES. Logistic regression analysis was used to compare the participation rate, positivity rate, colonoscopy uptake, positive predictive value (PPV) and detection rate across the SES groups. RESULTS: Participation to FIT screening was significantly lower for Quintile 5 (67.0%) compared to the other Quintiles (73.0% to 75.1%; adjusted OR quintile 5 versus quintile 1: 0.73, 95%CI: 0.72-0.74), as well as colonoscopy uptake after a positive FIT (adjusted OR 0.73, 95%CI: 0.69-0.77). The detection rate per FIT participant for advanced neoplasia gradually increased from 3.3% in Quintile 1 to 4.0% in Quintile 5 (adjusted OR 1.20%, 95%CI 1.16-1.24). As a result of lower participation, the yield per invitee was similar for Quintile 5 (2.04%) and Quintile 1 (2.00%), both being lower than Quintiles 2 to 4 (2.20%-2.28%). CONCLUSIONS: Screening has the potential to reduce health inequalities in CRC mortality, because of a higher detection in participants with a lower SES. However, in the Dutch screening programme, this is currently offset by the lower participation in this group.

Strongly Divergent Impact of Adherence Patterns on Efficacy of Colorectal Cancer Screening: The Need to Refine Adherence Statistics.

INTRODUCTION: The performance of colorectal cancer (CRC) screening programs depends on the adherence to screening offers. However, identical adherence levels may result from varying patterns of the population's screening behavior. We quantified the effects of different adherence patterns on the long-term performance of CRC screening for annual fecal immunochemical testing and screening colonoscopy at 10-year intervals. METHODS: Using a multistate Markov model, we simulated scenarios where, while at the same overall adherence level, a certain proportion of the population adheres to all screening offers (selective adherence) or the entire population uses the screening offers at some point(s) of time, albeit not in the recommended frequency (sporadic adherence). Key outcomes for comparison were the numbers of prevented CRC cases and prevented CRC deaths after 50 simulated years. RESULTS: For screening with annual fecal immunochemical testing at adherence levels of 10%-50%, ratios of prevented CRC cases (CRC deaths) resulting from a sporadic vs a selective pattern ranged from 1.8 to 4.4 (1.9-5.3) for men and from 1.7 to 3.6 (1.8-4.4) for women, i.e., up to 4-5 times more CRC cases and deaths were prevented when the population followed a sporadic instead of a selective adherence pattern. Comparisons of simulated scenarios for screening colonoscopy revealed similar patterns. DISCUSSION: Over a lifelong time frame, large numbers of irregular screening attendees go along with much larger preventive effects than small numbers of perfectly adhering individuals. In clinical practice, efforts to reach as many people as possible at least sporadically should be prioritized over efforts to maximize adherence to repeat screening offers.

Factors predicting improved compliance towards colonoscopy in individuals with positive faecal immunochemical test (FIT).

OBJECTIVES: Follow-up colonoscopy after a positive faecal immunochemical test (FIT) in any colorectal cancer (CRC) screening programme is integral. However, many individuals who had a positive FIT declined colonoscopy subsequently. This study aims to uncover the predictors on completion of colonoscopy using the Health Belief Model (HBM) between individuals who complete and those who did not after a positive FIT. METHODS: A mixed-method study comprising qualitative semi-structured interviews followed by a locally validated questionnaire in Singapore was prospectively administered via telephone interview to average risk individuals with positive FIT results from a cohort of the national FIT screening database referred for follow-up colonoscopic evaluation. RESULTS: A total of 394 individuals, with a median age of 66 years (range, 46-89 years), were recruited. Fifty percent completed follow-up colonoscopic evaluation and formed the "doers" group. All participants demonstrated high knowledge of symptoms of CRC and awareness and qualitative responses were aligned to the various HBM domains. Using multi-variable analysis, doers felt that medical recommendations (odds ratio [OR], 2.39, 95% confidence interval [CI]: 1.23-4.63, p = 0.01) and mainstream media publicity (OR, 2.16, 95% CI: 1.09-4.26, p = 0.026) were important. Non-doers showed positive association with perceived barriers such as cost (OR, 2.15, 95% CI: 1.10-4.20, p = 0.026) and inconvenience (OR, 3.44, 95% CI: 1.50-7.89, p = 0.004). CONCLUSIONS: Identified factors such as tackling perceived barriers, public health education and active promotion by medical physicians, family and friends could help guide subsequent interventions to improve compliance of individuals with positive FIT to undergo follow-up colonoscopy.

Optimizing Positivity Thresholds for a Risk-Adapted Screening Strategy in Colorectal Cancer Screening.

INTRODUCTION: Risk-adapted screening combining the Asia-Pacific Colorectal Screening score, fecal immunochemical test (FIT), and colonoscopy improved the yield of colorectal cancer screening than FIT. However, the optimal positivity thresholds of risk scoring and FIT of such a strategy warrant further investigation. METHODS: We included 3,407 participants aged 50-74 years undergoing colonoscopy from a colorectal cancer screening trial. For the risk-adapted screening strategy, subjects were referred for subsequent colonoscopy or FIT according to their risk scores. Diagnostic performance was evaluated for FIT and the risk-adapted screening method with various positivity thresholds. Furthermore, a modeled screening cohort was established to compare the yield and cost using colonoscopy, FIT, and the risk-adapted screening method in a single round of screening. RESULTS: Risk-adapted screening method had higher sensitivity for advanced neoplasm (AN) (27.6%-76.3% vs 13.8%-17.3%) but lower specificity (46.6%-90.8% vs 97.4%-98.8%) than FIT did. In a modeled screening cohort, FIT-based screening would be slightly affected because the threshold varied with a reduction of 76.0%-80.9% in AN detection and 82.0%-84.4% in cost when compared with colonoscopy. By contrast, adjusting the threshold of Asia-Pacific Colorectal Screening score from 3 to 5 points for risk-adapted screening varied from an increase of 12.6%-14.1% to a decrease of 55.6%-60.1% in AN detection, with the reduction of cost from 4.2%-5.3% rising to 66.4%-68.5%. DISCUSSION: With an appropriate positivity threshold tailored to clinical practice, the risk-adapted screening could save colonoscopy resources and cost compared with the colonoscopy-only and FIT-only strategies.

Potential contribution of ELISA and LFI assays to assessment of the oxidative stress condition based on 8-oxodG biomarker.

Immunoassays have been extensively applied in the medical diagnostic field. Enzyme-Linked Immunosorbent Assay (ELISA) and Lateral Flow Immunochemical Assay (LFIA) are methods that have been well established to analysis of clinical substances such as protein, hormones, drugs, identification of antibodies and in the quantification of antigen. Over the past years, the application of these methods has been extended to assess the clinical oxidative stress condition based on monitoring of the 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) biomarker levels. The present manuscript provides an overview of the current immunoassays based on ELISA and LFIA technologies applied for a quantitative analysis of the 8-oxodG. The discussion focuses on the principles of development, improvement and analytical performance of these assays. The relationship of the molecule 8-oxodG as a clinical biomarker of the assessment of the oxidative stress condition is also discussed. Commercially available products to 8-oxodG analysis are also presented.

Age-specific sequence of colorectal cancer screening options in Germany: A model-based critical evaluation.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

Application of Behavioral Economics Principles Improves Participation in Mailed Outreach for Colorectal Cancer Screening.

INTRODUCTION: Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality in the United States. Although various interventions have improved screening rates, they often require abundant resources and can be difficult to implement. Social psychology and behavioral economics principles offer an opportunity for low-cost and easy-to-implement strategies but are less common in clinical settings. METHODS: We randomized 2,000 patients aged 50-75 years eligible for CRC screening to one of the 2 mailed interventions: a previously used text-based letter describing and offering fecal immunochemical testing (FIT) and colonoscopy (usual care arm); or a letter leveraging social psychology and behavioral economics principles (e.g., implied scarcity and choice architecture), minimal text, and multiple images to offer FIT and colonoscopy (intervention arm). We compared total screening uptake, FIT uptake, and colonoscopy uptake at 1-month intervals in each group. RESULTS: There were 1,882 patients included in the final analysis. The mean age was 69.3 years, and baseline characteristics in the 2 groups were similar. Screening completion at 26 weeks was 19.5% in the usual care arm (16.3% FIT vs 3.2% colonoscopy, P < 0.01) and 24.1% in the intervention arm (22.1% FIT vs 2.0% colonoscopy, P < 0.01) (P = 0.02). DISCUSSION: Among primary care patients aged 50-75 years in an academic setting, mailed CRC outreach employing social psychology and behavioral economics principles led to a higher participation in CRC screening than usual care mailed outreach. TRANSLATIONAL IMPACT: Mailed interventions to increase CRC screening should incorporate social psychology and behavioral economics principles to improve participation.

Utility of fecal immunochemical test vs guaiac fecal occult blood test for assessment of gastrointestinal bleed in hospitalized patients.

BACKGROUND: Guaiac fecal occult blood testing (gFOBT) is often used "off-label" for gastrointestinal (GI) bleeding. Fecal Immunochemical Test (FIT) is increasingly replacing gFOBT in colorectal cancer screening and may play a role in assessment for significant bowel disease. We examined the concordance of FIT with gFOBT (Hemoccult Sensa II) among inpatients and between day 1 and day 3 gFOBT results. METHODS: FIT was performed alongside gFOBT on all inpatient stool sent for occult blood to the Winnipeg Health Sciences Centre laboratory over 1 y. gFOBT was performed on days 1 and 3 post stool collection, while FIT was performed on day 1 only. RESULTS: Positivity rates were highest for Day 1 gFOBT (27.7%), and lowest for FIT (18.3%). Concordance between FIT and Days 1 and 3 gFOBT for negative test results (96.4% and 94.1%) was significantly higher than that expected by chance alone (58.7% and 61.3%, P < .001). Similarly, concordance for positive test results (55.8% and 55.6%) was significantly higher as well as for days 1 and 3 gFOBT results. CONCLUSIONS: We found no benefit in delayed testing for 3 days post collection. FIT provides equivalent results to gFOBT in hospitalized patients.

Efficacy and cost-effectiveness of fecal immunochemical test versus colonoscopy in colorectal cancer screening: a systematic review and meta-analysis.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Sequential Assessment of Multiple Epigenetic Modifications of Cytosine in Whole Genomic DNA by Surface Plasmon Resonance.

Since the discovery of the active DNA demethylation pathway in mammals, numerous efforts have been made to distinguish epigenetic cytosine variants, including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). However, the rapid discrimination of multiple cytosine variants in DNA remains challenging because the conventional assays require time-consuming DNA pretreatments, such as enzymatical digestion and chemical conversion. Here we demonstrated the high-throughput discrimination of four cytosine variants in DNA by using a sequential surface-plasmon-resonance (SPR)-based immunochemical assay. The target DNAs were biotinylated in one step with a bifunctional linker 1 and robustly immobilized on a streptavidin-coated sensor surface to hold them in place during an alkali washing designed to remove residual antibodies. By repeating the injection of antibodies and washing, we achieved a sequential assessment of cytosine variants in identical DNA and identified the yield of in vitro 5mC oxidation in genomic DNA by the ten-eleven translocation 1 (TET1) enzyme. These results demonstrated that our sequential SPR-based immunochemical assay was effective for evaluating multiple epigenetic modifications in a whole genome with a single row operation without time-consuming DNA pretreatments.

Cost-Effectiveness and National Effects of Initiating Colorectal Cancer Screening for Average-Risk Persons at Age 45 Years Instead of 50 Years.

BACKGROUND & AIMS: The American Cancer Society has recommended initiating colorectal cancer (CRC) screening at age 45 years instead of 50 years. We estimated the cost effectiveness and national effects of adopting this recommendation. METHODS: We compared screening strategies and alternative resource allocations in a validated Markov model. We based national projections on screening participation rates by age and census data. RESULTS: Screening colonoscopy initiation at age 45 years instead of 50 years in 1000 persons averted 4 CRCs and 2 CRC deaths, gained 14 quality-adjusted life-years (QALYs), cost $33,900/QALY gained, and required 758 additional colonoscopies. These 758 colonoscopies could instead be used to screen 231 currently unscreened 55-year-old persons or 342 currently unscreened 65-year-old persons, through age 75 years. These alternatives averted 13-14 CRC cases and 6-7 CRC deaths and gained 27-28 discounted QALYs while saving $163,700-$445,800. Improving colonoscopy completion rates after abnormal results from a fecal immunochemical test yielded greater benefits and savings. Initiation of fecal immunochemical testing at age 45 years instead of 50 years cost $7700/QALY gained. Shifting current age-specific screening rates to 5 years earlier could avert 29,400 CRC cases and 11,100 CRC deaths over the next 5 years but would require 10.7 million additional colonoscopies and cost an incremental $10.4 billion. Improving screening rates to 80% in persons who are 50-75 years old would avert nearly 3-fold more CRC deaths at one third the incremental cost. CONCLUSIONS: In a Markov model analysis, we found that starting CRC screening at age 45 years is likely to be cost effective. However, greater benefit, at lower cost, could be achieved by increasing participation rates for unscreened older and higher-risk persons.

Mailed Outreach Is Superior to Usual Care Alone for Colorectal Cancer Screening in the USA: A Systematic Review and Meta-analysis.

Mailed outreach promoting colorectal cancer (CRC) screening with a stool blood test kit may increase participation, but magnitude and consistency of benefit of this intervention strategy is uncertain. Our aim was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing mailed outreach offering stool tests to usual care, clinic-based screening offers on CRC screening uptake in the USA. We performed a systematic literature search of five databases for RCTs of mailed outreach from January 1980 through June 2017. Primary outcome was screening completion, summarized using random-effects meta-analysis as pooled differences in proportion completing the screening and relative risk of achieving screening compared to control. Subgroup analyses by test type offered-fecal immunochemical test (FIT) or guaiac fecal occult blood test (gFOBT), the presence of telephone reminders, and the presence of predominant underserved/minority population within study were performed. Quality of evidence was evaluated using the GRADE framework. Seven RCTs which enrolled 12,501 subjects were included (n = 5703 assigned mailed outreach and n = 6798 usual care). Mailed outreach resulted in a 28% absolute (95% CI 25-30%; I2 = 47%) and a 2.8-fold relative (RR 2.65, 95% CI 2.03-3.45; I2 = 92%) increase in screening completion compared to usual care, with a number needed to invite estimated to be 3.6. Similar outcomes were observed across subgroups. Overall body of evidence was at moderate quality. Mailed outreach offering a gFOBT or FIT is associated with a large and consistent increase in CRC screening completion and should be considered for more widespread implementation for improving screening rates nationwide.

Impact of a mass media campaign on participation rates in a National Bowel Cancer Screening Program: a field experiment.

OBJECTIVES AND DESIGN: This field experiment aimed to compare bowel cancer screening participation rates prior to, during and after a mass media campaign promoting screening, and the extent to which a higher intensity campaign in one state led to higher screening rates compared with another state that received lower intensity campaign exposure. INTERVENTION: An 8-week television-led mass media campaign was launched in selected regions of Australia in mid-2014 to promote Australia's National Bowel Cancer Screening Program (NBCSP) that posts out immunochemical faecal occult blood test (iFOBT) kits to the homes of age-eligible people. The campaign used paid 30-second television advertising in the entire state of Queensland but not at all in Western Australia. Other supportive campaign elements had national exposure, including print, 4-minute television advertorials, digital and online advertising. OUTCOME MEASURES: Monthly kit return and invite data from NBCSP (January 2012 to December 2014). Return rates were determined as completed kits returned for analysis out of the number of people invited to do the iFOBT test in the current and past 3 months in each state. RESULTS: Analyses adjusted for seasonality and the influence of other national campaigns. The number of kits returned for analysis increased in Queensland (adjusted rate ratio 20%, 95% CI 1.06% to 1.35%, p<0.01) during the months of the campaign and up to 2 months after broadcast, but only showed a tendency to increase in Western Australia (adjusted rate ratio 11%, 95% CI 0.99% to 1.24%, p=0.087). CONCLUSIONS: The higher intensity 8-week television-led campaign in Queensland increased the rate of kits returned for analysis in Queensland, whereas there were marginal effects for the low intensity campaign elements in Western Australia. The low levels of participation in Australia's NBCSP could be increased by national mass media campaigns, especially those led by higher intensity paid television advertising.

Barriers and Facilitators of Colorectal Cancer Screening in a Federally Qualified Health Center (FQHC).

INTRODUCTION: Colorectal cancer is a leading cause of cancer-related mortality in the United States. Current screening recommendations for individuals aged 50 to 75 years include colonoscopy every 10 years, flexible sigmoidoscopy every 5 years, or annual stool-based testing. Stool-based testing, including fecal immunochemical tests (FITs), are cost effective, easy to perform at home, and noninvasive, yet many patients fail to return testing kits and go unscreened. The purpose of the study was to identify patient characteristics and perceived barriers and facilitators of FIT return. METHODS: Patients in a large, federally qualified health center who received a FIT kit order between January 1 and July 1, 2017 were identified. We compared sociodemographic and health characteristics between patients who returned and did not return FITs. We used telephone surveys to nonreturners to identify potential barriers (cost, knowledge, psychosocial factors) and facilitators (prepaid postage, outreach) of FIT kit return. An online survey of clinicians assessed perceived patient barriers and facilitators of colorectal cancer screening. RESULTS: Of the 875 patients who received a FIT order, 435 (49.7%) did not return the kit and 121 of the nonreturners completed a telephone survey. Current smokers had an increased risk of FIT nonreturn compared with never smokers (RR = 1.32; 95% CI, 1.13-1.54). Forgetfulness and lack of motivation were the most common FIT return barriers perceived by both patients and clinicians. Prepaid postage with return address on FIT return envelopes and live call reminders were the most commonly reported facilitators. Barriers and facilitators varied greatest between English- and Spanish-speaking patients. CONCLUSION: In this study, the most common perceived barriers to return of screening fecal test kits were forgetfulness and lack of motivation. The most common perceived facilitators were live call reminders and postage-paid return envelopes. Understanding barriers and facilitators to FITs may be necessary to enhance cancer screening rates in underserved patient populations.

Faecal immunochemical tests versus colonoscopy for post-polypectomy surveillance: an accuracy, acceptability and economic study.

BACKGROUND: In the UK, patients with one or two adenomas, of which at least one is ≥ 10 mm in size, or three or four small adenomas, are deemed to be at intermediate risk of colorectal cancer (CRC) and referred for surveillance colonoscopy 3 years post polypectomy. However, colonoscopy is costly, can cause discomfort and carries a small risk of complications. OBJECTIVES: To determine whether or not annual faecal immunochemical tests (FITs) are effective, acceptable and cost saving compared with colonoscopy surveillance for detecting CRC and advanced adenomas (AAs). DESIGN: Diagnostic accuracy study with health psychology assessment and economic evaluation. SETTING: Participants were recruited from 30 January 2012 to 30 December 2013 within the Bowel Cancer Screening Programme in England. PARTICIPANTS: Men and women, aged 60-72 years, deemed to be at intermediate risk of CRC following adenoma removal after a positive guaiac faecal occult blood test were invited to participate. Invitees who consented and returned an analysable FIT were included. INTERVENTION: We offered participants quantitative FITs at 1, 2 and 3 years post polypectomy. Participants testing positive with any FIT were referred for colonoscopy and not offered further FITs. Participants testing negative were offered colonoscopy at 3 years post polypectomy. Acceptibility of FIT was assessed using discussion groups, questionnaires and interviews. MAIN OUTCOME MEASURES: The primary outcome was 3-year sensitivity of an annual FIT versus colonoscopy at 3 years for detecting advanced colorectal neoplasia (ACN) (CRC and/or AA). Secondary outcomes included participants' surveillance preferences, and the incremental costs and cost-effectiveness of FIT versus colonoscopy surveillance. RESULTS: Of 8008 invitees, 5946 (74.3%) consented and returned a round 1 FIT. FIT uptake in rounds 2 and 3 was 97.2% and 96.9%, respectively. With a threshold of 40 µg of haemoglobin (Hb)/g faeces (hereafter referred to as µg/g), positivity was 5.8% in round 1, declining to 4.1% in round 3. Over three rounds, 69.2% (18/26) of participants with CRC, 34.3% (152/443) with AAs and 35.6% (165/463) with ACN tested positive at 40 µg/g. Sensitivity for CRC and AAs increased, whereas specificity decreased, with lower thresholds and multiple rounds. At 40 µg/g, sensitivity and specificity of the first FIT for CRC were 30.8% and 93.9%, respectively. The programme sensitivity and specificity of three rounds at 10 µg/g were 84.6% and 70.8%, respectively. Participants' preferred surveillance strategy was 3-yearly colonoscopy plus annual FITs (57.9%), followed by annual FITs with colonoscopy in positive cases (31.5%). FIT with colonoscopy in positive cases was cheaper than 3-yearly colonoscopy (£2,633,382), varying from £485,236 (40 µg/g) to £956,602 (10 µg/g). Over 3 years, FIT surveillance could miss 291 AAs and eight CRCs using a threshold of 40 µg/g, or 189 AAs and four CRCs using a threshold of 10 µg/g. CONCLUSIONS: Annual low-threshold FIT with colonoscopy in positive cases achieved high sensitivity for CRC and would be cost saving compared with 3-yearly colonoscopy. However, at higher thresholds, this strategy could miss 15-30% of CRCs and 40-70% of AAs. Most participants preferred annual FITs plus 3-yearly colonoscopy. Further research is needed to define a clear role for FITs in surveillance. FUTURE WORK: Evaluate the impact of ACN missed by FITs on quality-adjusted life-years. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18040196. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment programme, NIHR Imperial Biomedical Research Centre and the Bobby Moore Fund for Cancer Research UK. MAST Group Ltd provided FIT kits.

Faecal immunochemical tests for haemoglobin (FIT) in the assessment of patients with lower abdominal symptoms: current controversies.

Faecal immunochemical tests for haemoglobin (FIT), as an adjunct to clinical information, assist in the triage of patients presenting in primary care with lower abdominal symptoms. Controversy remains regarding whether and which qualitative and quantitative FIT can be used, which groups of patients would benefit most from FIT, whether FIT should be done in primary and/or secondary care, and how FIT should be incorporated into diagnostic pathways. Controversy also exists as to the optimum cut-off used for referral for colonoscopy. A single sample of faeces may be sufficient. Reporting of results requires consideration. FIT provide a good rule in test for colorectal cancer and a good rule out test for significant bowel disease, but robust safety-netting is required for patients with negative results and ongoing symptoms. Risk scoring models have been developed, but their value is unclear as yet. Further evaluation of these topics is required to inform good practice.

Cost-effectiveness of colorectal cancer screening programmes using sigmoidoscopy and immunochemical faecal occult blood test.

OBJECTIVE: Several European countries are implementing organized colorectal cancer (CRC) screening programmes using faecal immunochemical test (FIT) and/or flexible sigmoidoscopy (FS), but the cost-effectiveness of these programmes is not yet available. We aimed to assess cost-effectiveness, based on data from the established Piedmont screening programme. METHODS: Using the Piedmont programme data, a Markov model was constructed comparing three strategies in a simulated cohort of 100,000 subjects: single FS, biennial FIT, or sequential strategy (FS + FIT offered to FS non-responders). Estimates for CRC incidence and mortality prevention were derived from studies of organized screening. Cost analysis for FS and FIT was based on data from organized programmes. Incremental cost-effectiveness ratios (ICER) between the different strategies were calculated. Sensitivity and probabilistic analyses were performed. RESULTS: Direct costs for FS, and for FIT at first and subsequent rounds, were estimated as €160, €33, and €21, respectively. All the simulated strategies were effective (10-17% CRC incidence reduction) and cost-effective vs. no screening (ICER <€1000 per life-year saved). FS and FS + FIT were the only cost-saving strategies, with FS least expensive (€15 saving per person invited). FS + FIT and FS were the only non-dominated strategies. FS + FIT were more effective and cost-effective than FS (ICER €1217 per life-year saved). The residual marginal uncertainty was mainly related to parameters inherent to FIT effectiveness and adherence. CONCLUSIONS: Organized CRC screening programmes are highly cost-effective, irrespective of the test selected. A sequential approach with FS and FIT appears the most cost-effective option. A single FS is the least expensive, but convenient, approach.

Attitudes towards faecal immunochemical testing in patients at increased risk of colorectal cancer: an online survey of GPs in England.

BACKGROUND: There is increasing interest in using a quantitative faecal immunochemical test (FIT) to rule out colorectal cancer (CRC) in patients with high-risk symptoms in primary care. AIM: This study aimed to investigate GPs' attitudes and willingness to use a FIT over an urgent 2-week wait (2WW) referral. DESIGN AND SETTING: A cross-sectional online survey involving 1024 GPs working across England. METHOD: Logistic regression models were used to explore the likelihood of GPs using a FIT instead of a 2WW referral, and reported using odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Just over one-third of GPs (n = 365) preferred to use a FIT as a rule-out test over a 2WW referral. GPs were more willing if they were: aged 36-45 years (OR 1.59 [95% CI = 1.04 to 2.44]); 46-55 years (OR 1.99 [95% CI = 1.14 to 3.47]); thought a FIT was highly accurate (OR 1.63 [95% CI = 1.16 to 2.29]); thought patients would benefit compared with having a colonoscopy (OR 2.02 [95% CI = 1.46 to 2.79]); and were highly confident about discussing the benefits of a FIT (OR 2.14 [95% CI = 1.46 to 3.16]). GPs were less willing if they had had >10 urgent referrals in the past year (OR 0.62 [95% CI = 0.40 to 0.94]) and thought that longer consultations would be needed (OR 0.61 [95% CI = 0.44 to 0.83]). CONCLUSION: The study findings suggest that the acceptability of using a FIT as a rule-out test in primary care is currently low, with less than half of GPs who perceived the test to be accurate preferring it over colonoscopy. Any potential guideline changes recommending a FIT in patients with high-risk symptoms, instead of urgent referral to rule out CRC, are likely to require intensive supporting educational outreach to increase GP confidence in the accuracy and application of a FIT in this context.