Increased uptake and improved outcomes of bowel cancer screening with a faecal immunochemical test: results from a pilot study within the national screening programme in England
TL;DR: High positivity rates, particularly in men and previous non-respondents, challenge the available colonoscopy resource, but improvements in neoplasia detection are still achievable within this limited resource.
Abstract: Background The National Health Service Bowel Cancer Screening Programme (BCSP) in England uses a guaiac-based faecal occult blood test (gFOBt). A quantitative faecal immunochemical test (FIT) for haemoglobin (Hb) has many advantages, including being specific for human blood, detecting Hb at a much lower concentration with a single faecal sample and improved uptake. Methods In 2014, a large comparative pilot study was performed within BCSP to establish the acceptability and diagnostic performance of FIT. Over a 6-month period, 40 930 (1 in 28) subjects were sent a FIT (OC-SENSOR) instead of a gFOBt. A bespoke FIT package was used to mail FIT sampling devices to and from FIT subjects. All participants positive with either gFOBt or FIT (cut-off 20 µg Hb/g faeces) were referred for follow-up. Subgroup analysis included cut-off concentrations, age, sex, screening history and deprivation quintile. Results While overall uptake increased by over 7 percentage points with FIT (66.4% vs 59.3%, OR 1.35, 95% CI 1.33 to 1.38), uptake by previous non-responders almost doubled (FIT 23.9% vs gFOBt 12.5%, OR 2.20, 95% CI 2.10 to 2.29). The increase in overall uptake was significantly higher in men than women and was observed across all deprivation quintiles. With the conventional 20 µg/g cut-off, FIT positivity was 7.8% and ranged from 5.7% in 59–64-year-old women to 11.1% in 70–75-year-old men. Cancer detection increased twofold and that for advanced adenomas nearly fivefold. Detection rates remained higher with FIT for advanced adenomas, even at 180 µg Hb/g. Conclusions Markedly improved participation rates were achieved in a mature gFOBt-based national screening programme and disparities between men and women were reduced. High positivity rates, particularly in men and previous non-respondents, challenge the available colonoscopy resource, but improvements in neoplasia detection are still achievable within this limited resource.
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TL;DR: The higher mortality of colorectal cancer in men appears to be a result of exogenous and/or endogenous factors pre-diagnosis that lead to higher incidence rates, however, sex and gender differences that suggest more targeted interventions may facilitate prevention and earlier diagnosis in both men and women are suggested.
Abstract: Colorectal cancer (CRC) is an illness strongly influenced by sex and gender, with mortality rates in males significantly higher than females. There is still a dearth of understanding on where sex differences exist along the pathway from presentation to survival. The aim of this review is to identify where actions are needed to improve outcomes for both sexes, and to narrow the gap for CRC. A cross-sectional review of national data was undertaken to identify sex differences in incidence, screening uptake, route to diagnosis, cancer stage at diagnosis and survival, and their influence in the sex differences in mortality. Overall incidence is higher in men, with an earlier age distribution, however, important sex differences exist in anatomical site. There were relatively small differences in screening uptake, route to diagnosis, cancer staging at diagnosis and survival. Screening uptake is higher in women under 69 years. Women are more likely to present as emergency cases, with more men diagnosed through screening and two-week-wait. No sex differences are seen in diagnosis for more advanced disease. Overall, age-standardised 5-year survival is similar between the sexes. As there are minimal sex differences in the data from routes to diagnosis to survival, the higher mortality of colorectal cancer in men appears to be a result of exogenous and/or endogenous factors pre-diagnosis that lead to higher incidence rates. There are however, sex and gender differences that suggest more targeted interventions may facilitate prevention and earlier diagnosis in both men and women.
196 citations
John Radcliffe Hospital1, Western Sussex Hospitals NHS Foundation Trust2, Raigmore Hospital3, Cardiff and Vale University Health Board4, University of Nottingham5, West Middlesex University Hospital6, Imperial College London7, University College London8, Leeds Teaching Hospitals NHS Trust9, University of Sheffield10, Public Health England11, Newcastle University12
TL;DR: These consensus guidelines are the first guidelines that take into account the introduction of national bowel cancer screening and incorporate surveillance of patients following resection of either adenomatous or serrated polyps and also post-colorectal cancer resection.
Abstract: These consensus guidelines were jointly commissioned by the British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and Public Health England (PHE). They provide an evidence-based framework for the use of surveillance colonoscopy and non-colonoscopic colorectal imaging in people aged 18 years and over. They are the first guidelines that take into account the introduction of national bowel cancer screening. For the first time, they also incorporate surveillance of patients following resection of either adenomatous or serrated polyps and also post-colorectal cancer resection. They are primarily aimed at healthcare professionals, and aim to address: Which patients should commence surveillance post-polypectomy and post-cancer resection? What is the appropriate surveillance interval? When can surveillance be stopped? two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument provided a methodological framework for the guidelines. The BSG’s guideline development process was used, which is National Institute for Health and Care Excellence (NICE) compliant. two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The key recommendations are that the high-risk criteria for future colorectal cancer (CRC) following polypectomy comprise either: two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps This cohort should undergo a one-off surveillance colonoscopy at 3 years. Post-CRC resection patients should undergo a 1 year clearance colonoscopy, then a surveillance colonoscopy after 3 more years.
189 citations
TL;DR: Close monitoring of the implementation of the Dutch national CRC screening program allowed for instant adjustment of the FIT cut-off levels to optimize program performance.
167 citations
TL;DR: The diagnostic yield was not optimal using colonoscopy screening in high-risk populations given the relatively low participation rate, and several factors including age, sex, family history of CRC, dietary intake of processed meat and smoking were identified to be associated with the presence of colorectal neoplasms.
Abstract: Objective Colorectal cancer (CRC) screening has been widely implemented in many countries. However, evidence on participation and diagnostic yield of population-based CRC screening in China is sparse. Design The analyses were conducted in the context of the Cancer Screening Program in Urban China, which recruited 1 381 561 eligible participants aged 40–69 years from 16 provinces in China from 2012 to 2015. 182 927 participants were evaluated to be high risk for CRC by an established risk score system and were subsequently recommended for colonoscopy. Participation rates and detection of colorectal neoplasms in this programme were reported and their associated factors were explored. Results 25 593 participants undertook colonoscopy as recommended, with participation rate of 14.0%. High level of education, history of faecal occult blood test, family history of CRC and history of colonic polyp were found to be associated with the participation in colonoscopy screening. Overall, 65 CRC (0.25%), 785 advanced adenomas (3.07%), 2091 non-advanced adenomas (8.17%) and 1107 hyperplastic polyps (4.33%) were detected. Detection rates of colorectal neoplasms increased with age and were higher for men. More advanced neoplasms were diagnosed in the distal colon/rectum (65.2%). Several factors including age, sex, family history of CRC, dietary intake of processed meat and smoking were identified to be associated with the presence of colorectal neoplasms. Conclusion The diagnostic yield was not optimal using colonoscopy screening in high-risk populations given the relatively low participation rate. Our findings will provide important references for designing effective population-based CRC screening strategies in the future.
136 citations
TL;DR: Blood‐based markers for the early detection of CRC are discovered and SNHG11 exhibited the greatest diagnostic ability to identify precancerous lesions and early‐stage tumour formation, indicating that SNHg11 may be a novel therapeutic target for the treatment of CRC and a potential biomarker for the late detection.
Abstract: Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer mortality worldwide. Emerging evidence indicates that tumour cells release substantial amounts of RNA into the bloodstream, in which RNA strongly resists RNases and is present at sufficient levels for quantitative analyses. Our study aimed to discover blood-based markers for the early detection of CRC and to ascertain their efficiency in discriminating healthy controls, patients with polyps and adenomas and cancer patients. We first analysed and screened ZFAS1, SNHG11, LINC00909 and LINC00654 in a bioinformatics database and then collected clinical plasma samples for preliminary small-scale analysis and further large-scale verification. We then explored the mechanism of dominant lncRNA SNHG11 expression in CRC by in vitro and in vivo assays. The combination of ZFAS1, SNHG11, LINC00909 and LINC00654 showed high diagnostic performance for CRC (AUC: 0.937), especially early-stage disease (AUC: 0.935). Plasma levels of the four candidate lncRNAs were significantly reduced in postoperative samples compared to preoperative samples. A panel including these four lncRNAs performed well in distinguishing patient groups with different stages of colon disease, and SNHG11 exhibited the greatest diagnostic ability to identify precancerous lesions and early-stage tumour formation. Mechanistically, high SNHG11 expression promotes proliferation and metastasis by targeting the Hippo pathway. Taken together, the data indicate that SNHG11 may be a novel therapeutic target for the treatment of CRC and a potential biomarker for the early detection of CRC.
107 citations
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TL;DR: Cutting mortality in the annually screened group was accompanied by improved survival in those with colorectal cancer and a shift to detection at an earlier stage of cancer.
Abstract: Background Although tests for occult blood in the feces are widely used to screen for colorectal cancers, there is no conclusive evidence that they reduce mortality from this cause. We evaluated a fecal occult-blood test in a randomized trial and documented its effectiveness. Methods We randomly assigned 46,551 participants 50 to 80 years of age to screening for colorectal cancer once a year, to screening every two years, or to a control group. Participants who were screened submitted six guaiac-impregnated paper slides with two smears from each of three consecutive stools. About 83 percent of the slides were rehydrated. Participants who tested positive underwent a diagnostic evaluation that included colonoscopy. Vital status was ascertained for all participants over 13 years of follow-up. A committee determined causes of death. A single pathologist determined the stage of cancer for each tissue specimen. Differences in mortality from colorectal cancer, the primary study end point, were monitored with the...
3,199 citations
TL;DR: Evidence from this study and other trials suggest that consideration should be given to a national programme of FOB screening to reduce CRC mortality in the general population.
2,778 citations
TL;DR: The findings indicate that biennial screening by FOB tests can reduce CRC mortality, and the effect of the removal of more precursor adenomas in the screening-group participants than in controls on CRC incidence.
2,494 citations
TL;DR: In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results.
Abstract: Background An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. Methods We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. Results Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P = 0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P = 0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. Conclusions In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.)
1,332 citations
TL;DR: Advice on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer and for those with inflammatory bowel disease is provided.
Abstract: The British Society of Gastroenterology (BSG) and the Association of Coloproctology for Great Britain and Ireland (ACPGBI) commissioned this update of the 2002 guidance. The aim, as before, is to provide guidance on the appropriateness, method and frequency of screening for people at moderate and high risk from colorectal cancer. This guidance provides some new recommendations for those with inflammatory bowel disease and for those at moderate risk resulting from a family history of colorectal cancer. In other areas guidance is relatively unchanged, but the recent literature was reviewed and is included where appropriate.
1,054 citations