Stephen P. Halloran

Inequalities in participation in an organized national colorectal cancer screening programme: results from the first 2.6 million invitations in England

BACKGROUND An organized, population-based, colorectal cancer screening programme was initiated in England in 2006 offering biennial faecal occult blood testing (FOBT) to adults aged 60-69 years. Organized screening programmes with no associated financial costs to the individual should minimize barriers to access for lower socio-economic status (SES) groups. However, SES differences in uptake were observed in the pilot centres of the UK programme, so the aim of this analysis was to identify the extent of inequalities in uptake by SES, ethnic diversity, gender and age in the first 28 months of the programme. Design Cross-sectional analysis of colorectal cancer screening uptake data. METHODS Between October 2006 and January 2009, over 2.6 million adults aged 60-69 years were mailed a first FOBT kit by the five regional screening hubs. Uptake was defined as return of a test kit within 13 weeks. We used multivariate generalized linear regression to examine variation by area-based socioeconomic deprivation, area-based ethnicity, gender and age. RESULTS Uptake was 54%, but showed a gradient across quintiles of deprivation, ranging from 35% in the most deprived quintile to 61% in the least deprived. Multivariate analyses confirmed an independent effect of deprivation, with stronger effects in women and older people. The most ethnically diverse areas also had lower uptake (38%) than other areas (52-58%) independent of SES, age, gender and regional screening hub. Ethnic disparities were more pronounced in men but equivalent across age groups. More women than men returned a kit (56 vs 51%), but there was also an interaction with age, with uptake increasing with age in men (49% at 60-64 years; 53% at 65-69 years) but not women (57 vs 56%). CONCLUSIONS Overall uptake rates in this organized screening programme were encouraging, but nonetheless there was low uptake in the most ethnically diverse areas and a striking gradient by SES. Action to promote equality of uptake is needed to avoid widening inequalities in cancer mortality.

A Proposal to Standardize Reporting Units for Fecal Immunochemical Tests for Hemoglobin

Fecal immunochemical tests for hemoglobin are replacing traditional guaiac fecal occult blood tests in population screening programs for many reasons. However, the many available fecal immunochemical test devices use a range of sampling methods, differ with regard to hemoglobin stability, and report hemoglobin concentrations in different ways. The methods for sampling, the mass of feces collected, and the volume and characteristics of the buffer used in the sampling device also vary among fecal immunochemical tests, making comparisons of test performance characteristics difficult. Fecal immunochemical test results may be expressed as the hemoglobin concentration in the sampling device buffer and, sometimes, albeit rarely, as the hemoglobin concentration per mass of feces. The current lack of consistency in units for reporting hemoglobin concentration is particularly problematic because apparently similar hemoglobin concentrations obtained with different devices can lead to very different clinical interpretations. Consistent adoption of an internationally accepted method for reporting results would facilitate comparisons of outcomes from these tests. We propose a simple strategy for reporting fecal hemoglobin concentration that will facilitate the comparison of results between fecal immunochemical test devices and across clinical studies. Such reporting is readily achieved by defining the mass of feces sampled and the volume of sample buffer (with confidence intervals) and expressing results as micrograms of hemoglobin per gram of feces. We propose that manufacturers of fecal immunochemical tests provide this information and that the authors of research articles, guidelines, and policy articles, as well as pathology services and regulatory bodies, adopt this metric when reporting fecal immunochemical test results.

Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper

Several randomized controlled trials have shown that population‐based screening using faecal occult blood testing (FOBT) can reduce mortality from colorectal neoplasia. Based on this evidence, a number of countries have introduced screening for colorectal cancer (CRC) and high‐risk adenoma and many others are considering its introduction. The aim of this article is to critically review the current status of faecal markers as population‐based screening tests for these neoplasia. Most of the available faecal tests involve the measurement of either occult blood or a panel of DNA markers. Occult blood may be measured using either the guaiac faecal occult blood test (gFOBT) or a faecal immunochemical test (iFOBT). Although iFOBT may require a greater initial investment, they have several advantages over gFOBT, including greater analytical sensitivity and specificity. Their use results in improved clinical performance and higher uptake rates. Importantly for population screening, some of the iFOBTs can be automated and provide an adjustable cutoff for faecal haemoglobin concentration. However, samples for iFOBT, may be less stable after collection than for gFOBT. For new centres undertaking FOBT for colorectal neoplasia, the European Group on Tumour Markers recommends use of a quantitative iFOBT with an adjustable cutoff point and high throughput analysis. All participants with positive FOBT results should be offered colonoscopy. The panel recommends further research into increasing the stability of iFOBT and the development of improved and affordable DNA and proteomic‐based tests, which reduce current false negative rates, simplify sample transport and enable automated analysis.

Influence of seasonal variations in ambient temperatures on performance of immunochemical faecal occult blood test for colorectal cancer screening: observational study from the Florence district

Background Faecal occult blood testing (FOBT) in population screening has proved to be effective in reducing mortality from colorectal cancer. In Italy a latex agglutination FOBT has been adopted for a single-sample screening programme. The aim of this study was to examine the performance of FOBTs in the Florence screening programme over several seasons to evaluate the impact of variations in ambient temperature on the performance of the screening test. Methods Measured haemoglobin (Hb) concentrations were aggregated into seasons with their average ambient temperature (AAT). Using logistic regression, the AAT over the period preceding the test measurement was analysed. This period included the time between faecal sampling and return of the test sample (mean 7 days) and the time in the laboratory refrigerator before analysis (mean 4 days). The AAT from days 5–11 before analysis of the test sample was considered a determinant of test positivity. The Kruskal–Wallis rank test was used to evaluate the significance of seasonal and/or AAT-related differences in Hb concentration. A logistic regression model adjusted for sex, age, season and screening episode (first or repeated examination) was constructed. Results 199 654 FOBT results were examined. Mean FOBT seasonal Hb concentrations (ng/ml) were: spring 27.6 (95% CI 26.2 to 29.1); summer 25.2 (95% CI 23.1 to 27.3); autumn 29.2 (95% CI 27.7 to 30.6); winter 29.5 (95% CI 27.9 to 31.1). Logistic regression showed that there was a 17% lower probability of the FOBT being positive in summer than in winter. The results of the logistic regression showed that an increase in temperature of 1°C produced a 0.7% reduction in probability of a FOBT being positive. In the summer the probability of detecting a cancer or an advanced adenoma was about 13% lower than in the winter. Conclusions This study showed that there is a significant fall in Hb concentration at higher ambient temperatures. These results will have important implications for the organisation of immunochemical FOBT-based screening programmes, particularly in countries with high ambient temperatures.

Colorectal cancer screening uptake over three biennial invitation rounds in the English bowel cancer screening programme

Objective To examine patterns of colorectal cancer (CRC) screening uptake over three biennial invitation rounds in the National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) in England. Methods We analysed data from the BCSPs Southern Hub for individuals (n=62 099) aged 60–64 years at the time of first invitation to screening with a follow-up period that allowed for two further biennial invitations. Data on sex, age and a neighbourhood-level measure of socioeconomic deprivation were used in the analysis. Outcomes included uptake of guaiac-based faecal occult blood (gFOB) test screening, inadequate gFOB screening (≥1 test kit(s) returned but failed to complete further gFOB tests needed to reach a conclusive test result), test positivity, compliance with follow-up examinations (usually colonoscopy) and diagnostic outcomes. Results Overall gFOB uptake was 57.4% in the first, 60.9% in the second and 66.2% in third biennial invitation round. This resulted in 70.1% of the initial cohort having responded at least once, 60.7% at least twice and 44.4% three times. Participation in the first round was strongly predictive of participation in the second round (‘Previous Responders’: 86.6% vs ‘Previous Non-Responders’: 23.1%). Participation in the third round was highest among ‘Consistent Screeners’ (94.5%), followed by ‘Late Entrants’ (78.0%), ‘Dropouts’ (59.8%) and ‘Consistent Non-Responders’ (14.6%). Socioeconomic inequalities in uptake were observed across the three rounds, but sex inequalities decreased over rounds. Inadequate gFOB screening was influenced by screening history and socioeconomic deprivation. Screening history was the only significant predictor of follow-up compliance. Conclusions Screening history is associated with overall gFOB uptake, inadequate gFOB screening and follow-up compliance. Socioeconomic deprivation is also consistently associated with lower gFOB uptake and inadequate gFOB screening. Improving regular screening among identified ‘at-risk’ groups is important for the effectiveness of CRC screening programmes.

Population screening for colorectal cancer means getting FIT: the past, present, and future of colorectal cancer screening using the fecal immunochemical test for hemoglobin (FIT).

Fecal immunochemical tests for hemoglobin (FIT) are changing the manner in which colorectal cancer (CRC) is screened. Although these tests are being performed worldwide, why is this test different from its predecessors? What evidence supports its adoption? How can this evidence best be used? This review addresses these questions and provides an understanding of FIT theory and practices to expedite international efforts to implement the use of FIT in CRC screening.

Advances in Fecal Occult Blood Tests: The FIT Revolution

There is a wide choice of fecal occult blood tests (FOBTs) for colorectal cancer screening. Goal: To highlight the issues applicable when choosing a FOBT, in particular which FOBT is best suited to the range of screening scenarios. Four scenarios characterize the constraints and expectations of screening programs: (1) limited colonoscopy resource with a need to constrain test positivity rate; (2) a priority for maximum colorectal neoplasia detection with little need to constrain colonoscopy workload; (3) an “adequate” endoscopy resource that allows balancing the benefits of detection with the burden of service provision; and (4) a need to maximize participation in screening. Guaiac-based FOBTs (gFOBTs) have significant deficiencies, and fecal immunochemical tests (FITs) for hemoglobin have emerged as better tests. gFOBTs are not sensitive to small bleeds, specificity can be affected by diet or drugs, participant acceptance can be low, laboratory quality control opportunities are limited, and they have a fixed hemoglobin concentration cutoff determining positivity. FITs are analytically more specific, capable of quantitation and hence provide flexibility to adjust cutoff concentration for positivity and the balance between sensitivity and specificity. FITs are clinically more sensitive for cancers and advanced adenomas, and because they are easier to use, acceptance rates are high. Conclusions: FOBT must be chosen carefully to meet the needs of the applicable screening scenario. Quantitative FIT can be adjusted to suit Scenarios 1, 2 and 3, and for each, they are the test of choice. FITs are superior to gFOBT for Scenario 4 and gFOBT is only suitable for Scenario 1.

Effects of evidence-based strategies to reduce the socioeconomic gradient of uptake in the English NHS Bowel Cancer Screening Programme (ASCEND): four cluster-randomised controlled trials

Summary Background Uptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the intention of improving the health benefits of screening. Methods All people eligible for screening (men and women aged 60–74 years) across England were included in four cluster-randomised trials. Randomisation was based on day of invitation. Each trial compared the standard information with the standard information plus the following supplementary interventions: trial 1 (November, 2012), a supplementary leaflet summarising the gist of the key information; trial 2 (March, 2012), a supplementary narrative leaflet describing peoples stories; trial 3 (June, 2013), general practice endorsement of the programme on the invitation letter; and trial 4 (July–August, 2013) an enhanced reminder letter with a banner that reiterated the screening offer. Socioeconomic status was defined by the Index of Multiple Deprivation score for each home address. The primary outcome was the socioeconomic status gradient in uptake across deprivation quintiles. This study is registered, number ISRCTN74121020. Findings As all four trials were embedded in the screening programme, loss to follow-up was minimal (less than 0·5%). Trials 1 (n=163 525) and 2 (n=150 417) showed no effects on the socioeconomic gradient of uptake or overall uptake. Trial 3 (n=265 434) showed no effect on the socioeconomic gradient but was associated with increased overall uptake (adjusted odds ratio [OR] 1·07, 95% CI 1·04–1·10, p<0·0001). In trial 4 (n=168 480) a significant interaction was seen with socioeconomic status gradient (p=0·005), with a stronger effect in the most deprived quintile (adjusted OR 1·11, 95% CI 1·04–1·20, p=0·003) than in the least deprived (1·00, 0·94–1·06, p=0·98). Overall uptake was also increased (1·07, 1·03–1·11, p=0·001). Interpretation Of four evidence-based interventions, the enhanced reminder letter reduced the socioeconomic gradient in screening uptake, but further reducing inequalities in screening uptake through written materials alone will be challenging. Funding National Institute for Health Research.

Comparing fecal immunochemical tests: improved standardization is needed.

The fecal immunochemical test (FIT) for hemoglobin has had a long and hard journey to acceptance in the S Proof of FIT superiority over the traditional guaiac fecal ccult blood tests was first demonstrated in an average risk merican population in 19961; however, the US has been low to embrace a technology that has clear analytical, oprational, and clinical advantages. American opinion leaders, he media,2 and some US colorectal cancer (CRC) guidelines ave consistently reinforced the philosophy that colonosopy every 10 years, beginning at age 50 years, is the preerred screening strategy.3 Some experts have suggested that FIT is a nonspecific marker for screen relevant neoplasia4 or is less effective than structural examinations of the colon for CRC prevention.5 Until recently, there have been few US studies evaluating the clinical effectiveness of FIT6; however, cross Europe and in some non-European countries, these tudies have provided a sound evidence base upon which opulation screening programs for CRC are being develped and implemented. The strength of this evidence is pparent in the recently published European Guidelines or Quality Assurance in Colorectal Cancer Screening and iagnosis, where FIT is recommended as the test of hoice for population-based screening.7 FIT are very specific markers of screen relevant neoplasia8,9 and many studies including the one in this issue of GASTROENTEROLOGY show that in only one round they identify approximately one third of the advanced adenomas present in an average risk, asymptomatic population and thus have the ability to prevent CRC as well as decrease mortality from it.10–12 A recent editorial suggested that a noninvasive, effecive, and inexpensive screening test for CRC could mean less arm to patients, more participation by underscreened roups, fewer opportunity costs to the healthcare system, nd a lower overall cost for CRC screening.13 The Denters et al12 study in this issue describes FIT perormance in a program of biennial testing over 2 screening ounds. It confirms the findings of other studies that FIT dentifies advanced adenomas, elicits better participation han guaiac FOBT, and that second-round participation ncreases in those previously screened (86%). The study hows that a negative first-round test reduces the odds of a iagnosis of advanced neoplasm at 2 years and that the dvanced neoplasms uncovered in the second screening a

Socioeconomic variation in uptake of colonoscopy following a positive faecal occult blood test result: a retrospective analysis of the NHS Bowel Cancer Screening Programme

Background:Bowel cancer is a serious health burden and its early diagnosis improves survival. The Bowel Cancer Screening Programme (BCSP) in England screens with the Faecal Occult Blood test (FOBt), followed by colonoscopy for individuals with a positive test result. Socioeconomic inequalities have been demonstrated for FOBt uptake, but it is not known whether they persist at the next stage of the screening pathway. The aim of this study was to assess the association between colonoscopy uptake and area socioeconomic deprivation, controlling for individual age and sex, and area ethnic diversity, population density, poor self-assessed health, and region.Methods:Logistic regression analysis of colonoscopy uptake using BCSP data for England between 2006 and 2009 for 24 180 adults aged between 60 and 69 years.Results:Overall colonoscopy uptake was 88.4%. Statistically significant variation in uptake is found between quintiles of area deprivation (ranging from 86.4 to 89.5%), as well as age and sex groups (87.9–89.1%), quintiles of poor self-assessed health (87.5–89.5%), non-white ethnicity (84.6–90.6%) and population density (87.9–89.3%), and geographical regions (86.4–90%).Conclusion:Colonoscopy uptake is high. The variation in uptake by socioeconomic deprivation is small, as is variation by subgroups of age and sex, poor self-assessed health, ethnic diversity, population density, and region.