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.

Effect of once-only flexible sigmoidoscopy screening on the outcomes of subsequent faecal occult blood test screening.

OBJECTIVE: To investigate the outcomes of biennial guaiac faecal occult blood test (gFOBT) screening after once-only flexible sigmoidoscopy (FS) screening. METHODS: Between 1994 and 1999, as part of the UK FS Screening Trial (UKFSST), adults aged 55-64 were randomly allocated to an intervention group (offered FS screening) or a control group (not contacted). From 2006, a subset of UKFSST participants (20,895/44,041 intervention group; 41,497/87,149 control group) were invited to biennial gFOBT screening by the English Bowel Cancer Screening Programme. We analysed gFOBT uptake, test positivity, yield of colorectal cancer (CRC), and positive predictive value (PPV) for CRC, advanced adenomas (AAs), and advanced colorectal neoplasia (ACN: AA/CRC). RESULTS: Uptake of gFOBT at first invitation was 1.9% lower (65.7% vs. 67.6%, p < 0.01) among intervention versus control group participants. Positivity was 0.4% lower (2.0% vs. 2.4%, p < 0.01) and CRC yield was 0.08% lower (0.19% vs. 0.27%, p = 0.14). PPVs were also lower in the intervention versus control group, at 10.3% vs. 12.3% ( p = 0.44) for CRC, 22.7% vs. 31.4% ( p < 0.01) for AA, and 33.0% vs. 43.7% ( p < 0.01) for ACN. Among those who refused FS ( n = 5532), gFOBT uptake at first invitation was 47.7%, CRC yield was 0.25%, and PPV for ACN was 46.2%. Among FS attenders ( n = 15,363), uptake was 72.2%, CRC yield was 0.18%, and PPV for ACN was 27.9%. CONCLUSIONS: Uptake, positivity and PPV of gFOBT screening were reduced following prior offer of FS screening. However, a quarter of FS screened participants receiving a diagnostic examination after positive gFOBT were diagnosed with ACN.

Faecal immunochemical tests (FIT) versus colonoscopy for surveillance after screening and polypectomy: a diagnostic accuracy and cost-effectiveness study.

OBJECTIVE: The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN: Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS: 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS: Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER: ISRCTN18040196; Results.

Whole-colon investigation vs. flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort study.

BACKGROUND: Patients with suspected colorectal cancer (CRC) usually undergo colonoscopy. Flexible sigmoidoscopy (FS) may be preferred if proximal cancer risk is low. We investigated which patients could undergo FS alone. METHODS: Cohort study of 7375 patients (≥55 years) referred with suspected CRC to 21 English hospitals (2004-2007), followed using hospital records and cancer registries. We calculated yields and number of needed whole-colon examinations (NNE) to diagnose one cancer by symptoms/signs and subsite. We considered narrow (haemoglobin <11 g/dL men; <10 g/dL women) and broad (<13 g/dL men; <12 g/dL women) anaemia definitions and iron-deficiency anaemia (IDA). RESULTS: One hundred and twenty-seven proximal and 429 distal CRCs were diagnosed. A broad anaemia definition identified 80% of proximal cancers; a narrow definition with IDA identified 39%. In patients with broad definition anaemia and/or abdominal mass, proximal cancer yield and NNE were 4.8% (97/2022) and 21. In patients without broad definition anaemia and/or abdominal mass, with rectal bleeding or increased stool frequency (41% of cohort), proximal cancer yield and NNE were 0.4% (13/3031) and 234. CONCLUSION: Most proximal cancers are accompanied by broad definition anaemia. In patients without broad definition anaemia and/or abdominal mass, with rectal bleeding or increased stool frequency, proximal cancer is rare and FS should suffice.

Number of Adenomas Removed and Colorectal Cancers Prevented in Randomized Trials of Flexible Sigmoidoscopy Screening.

BACKGROUND & AIMS: Screening for colorectal cancer (CRC) with sigmoidoscopy reduces CRC incidence by detecting and removing adenomas. The number needed to screen is a measure of screening efficiency, but is not directly associated with adenoma removal. We propose the following 2 new metrics for quantifying the relationship between adenoma removal and CRC prevented: number of adenomas needed to remove (NNR) and adenoma dwell time avoided (DTA). METHODS: We collected data from 4 randomized trials of sigmoidoscopy screening (1 in the United States and 3 in Europe) to assess NNR and DTA. For each trial, NNR was computed as the number of adenomas removed from subjects in the intervention group, divided by the number of CRCs prevented. DTA was computed similarly but taking into account the timing of adenoma removal. Combined results across trials were assessed using standard meta-analytic techniques. RESULTS: The estimated NNR for the PLCO (Prostate, Lung, Colorectal and Ovarian) trial was 74 (95% confidence interval [CI], 56-110), for the NORCCAP (Norwegian Colorectal Cancer Prevention) trial was 71 (95% CI, 44-174), for the SCORE (Screening for Colon Rectum) trial was 27 (95% CI, 14-135), and for the UKFSST (UK Flexible Sigmoidoscopy Screening Trial) was 36 (95% CI, 28-52). The combined estimate (meta-analysis) of NNR was 52 (95% CI, 36-93) assuming heterogeneity (P for heterogeneity = .014). DTA estimates among trials ranged from 278 to 730 years, with a combined estimate of 500 (95% CI, 344-833) years assuming heterogeneity (P for heterogeneity = .035), or 2 CRC cases prevented per 1000 adenoma dwell years avoided. The combined estimates of NNR and DTA restricted to advanced adenomas were 13 (95% CI, 9-22) and 122 (95% CI, 90-190) years, respectively. CONCLUSIONS: We collected data from 4 randomized trials of sigmoidoscopy screening for CRC to develop metrics of endoscopic efficiency, NNR and DTA, which are directly linked to adenoma detection and removal. They can be used to compare screening among endoscopic modalities and to more precisely measure adenoma to carcinoma transition rates.

High test positivity and low positive predictive value for colorectal cancer of continued faecal occult blood test screening after negative colonoscopy.

Objectives The English Bowel Cancer Screening Programme offers biennial guaiac faecal occult blood test (gFOBT) screening to 60-74-year-olds. Participants with positive results are referred for follow-up, but many do not have significant findings. If they remain age eligible, these individuals are reinvited for gFOBT screening. We evaluated the performance of repeat screening in this group. Methods We analysed data on programme participants reinvited to gFOBT screening after either previous negative gFOBT ( n = 327,542), or positive gFOBT followed by a diagnostic investigation negative for colorectal cancer (CRC) or adenomas requiring surveillance ( n = 42,280). Outcomes calculated were uptake, test positivity, yield of CRC, and positive predictive value (PPV) of gFOBT for CRC. Results For participants with a previous negative gFOBT, uptake in the subsequent screening round was 87.5%, positivity was 1.3%, yield of CRC was 0.112% of those adequately screened, and the PPV of gFOBT for CRC was 9.1%. After a positive gFOBT and a negative diagnostic investigation, uptake in the repeat screening round was 82.6%, positivity was 11.3%, CRC yield was 0.172% of participants adequately screened, and the PPV of gFOBT for CRC was 1.7%. Conclusion With high positivity and low PPV for CRC, the suitability of routine repeat gFOBT screening in two years among individuals with a previous positive test and a negative diagnostic examination needs to be carefully considered.

Is whole-colon investigation by colonoscopy, computerised tomography colonography or barium enema necessary for all patients with colorectal cancer symptoms, and for which patients would flexible sigmoidoscopy suffice? A retrospective cohort study.

BACKGROUND: For patients referred to hospital with suspected colorectal cancer (CRC), it is current standard clinical practice to conduct an examination of the whole colon and rectum. However, studies have shown that an examination of the distal colorectum using flexible sigmoidoscopy (FS) can be a safe and clinically effective investigation for some patients. These findings require validation in a multicentre study. OBJECTIVES: To investigate the links between patient symptoms at presentation and CRC risk by subsite, and to provide evidence of whether or not FS is an effective alternative to whole-colon investigation (WCI) in patients whose symptoms do not suggest proximal or obstructive disease. DESIGN: A multicentre retrospective study using data collected prospectively from two randomised controlled trials. Additional data were collected from trial diagnostic procedure reports and hospital records. CRC diagnoses within 3 years of referral were sourced from hospital records and national cancer registries via the Health and Social Care Information Centre. SETTING: Participants were recruited to the two randomised controlled trials from 21 NHS hospitals in England between 2004 and 2007. PARTICIPANTS: Men and women aged ≥ 55 years referred to secondary care for the investigation of symptoms suggestive of CRC. MAIN OUTCOME MEASURE: Diagnostic yield of CRC at distal (to the splenic flexure) and proximal subsites by symptoms/clinical signs at presentation. RESULTS: The data set for analysis comprised 7380 patients, of whom 59% were women (median age 69 years, interquartile range 62-76 years). Change in bowel habit (CIBH) was the most frequently presenting symptom (73%), followed by rectal bleeding (38%) and abdominal pain (29%); 26% of patients had anaemia. CRC was diagnosed in 551 patients (7.5%): 424 (77%) patients with distal CRC, 122 (22%) patients with cancer proximal to the descending colon and five patients with both proximal and distal CRC. Proximal cancer was diagnosed in 96 out of 2021 (4.8%) patients with anaemia and/or an abdominal mass. The yield of proximal cancer in patients without anaemia or an abdominal mass who presented with rectal bleeding with or without a CIBH or with a CIBH to looser and/or more frequent stools as a single symptom was low (0.5%). These low-risk groups for proximal cancer accounted for 41% (3032/7380) of the cohort; only three proximal cancers were diagnosed in 814 low-risk patients examined by FS (diagnostic yield 0.4%). LIMITATIONS: A limitation to this study is that changes to practice since the trial ended, such as new referral guidelines and improvements in endoscopy quality, potentially weaken the generalisability of our findings. CONCLUSIONS: Symptom profiles can be used to determine whether or not WCI is necessary. Most proximal cancers were diagnosed in patients who presented with anaemia and/or an abdominal mass. In patients without anaemia or an abdominal mass, proximal cancer diagnoses were rare in those with rectal bleeding with or without a CIBH or with a CIBH to looser and/or more frequent stools as a single symptom. FS alone should be a safe and clinically effective investigation in these patients. A cost-effectiveness analysis of symptom-based tailoring of diagnostic investigations for CRC is recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95152621. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 66. See the NIHR Journals Library website for further project information.

Reducing the socioeconomic gradient in uptake of the NHS bowel cancer screening Programme using a simplified supplementary information leaflet: a cluster-randomised trial.

BACKGROUND: Uptake of colorectal cancer screening is low in the English NHS Bowel Cancer Screening Programme (BCSP). Participation in screening is strongly associated with socioeconomic status. The aim of this study was to determine whether a supplementary leaflet providing the 'gist' of guaiac-based Faecal Occult Blood test (gFOBt) screening for colorectal cancer could reduce the socioeconomic status (SES) gradient in uptake in the English NHS BCSP. METHODS: The trial was integrated within routine BCSP operations in November 2012. Using a cluster randomised controlled design all adults aged 59-74 years who were being routinely invited to complete the gFOBt were randomised based on day of invitation. The Index of Multiple Deprivation was used to create SES quintiles. The control group received the standard information booklet ('SI'). The intervention group received the SI booklet and the Gist leaflet ('SI + Gist') which had been designed to help people with lower literacy engage with the invitation. Blinding of hubs was not possible and invited subjects were not made aware of a comparator condition. The primary outcome was the gradient in uptake across IMD quintiles. RESULTS: In November 2012, 163,525 individuals were allocated to either the 'SI' intervention (n = 79,104) or the 'SI + Gist' group (n = 84,421). Overall uptake was similar between the intervention and control groups (SI: 57.3% and SI + Gist: 57.6%; OR = 1.02, 95% CI: 0.92-1.13, p = 0.77). Uptake was 42.0% (SI) vs. 43.0% (SI + Gist) in the most deprived quintile and 65.6% vs. 65.8% in the least deprived quintile (interaction p = 0.48). The SES gradient in uptake was similar between the study groups within age, gender, hub and screening round sub-groups. CONCLUSIONS: Providing supplementary simplified information in addition to the standard information booklet did not reduce the SES gradient in uptake in the NHS BCSP. The effectiveness of the Gist leaflet when used alone should be explored in future research. TRIAL REGISTRATION: ISRCTN74121020 , registered: 17/20/2012.

The clinical effectiveness of different surveillance strategies to prevent colorectal cancer in people with intermediate-grade colorectal adenomas: a retrospective cohort analysis, and psychological and economic evaluations.

BACKGROUND: The UK guideline recommends 3-yearly surveillance for patients with intermediate-risk (IR) adenomas. No study has examined whether or not this group has heterogeneity in surveillance needs. OBJECTIVES: To examine the effect of surveillance on colorectal cancer (CRC) incidence; assess heterogeneity in risk; and identify the optimum frequency of surveillance, the psychological impact of surveillance, and the cost-effectiveness of alternative follow-up strategies. DESIGN: Retrospective multicentre cohort study. SETTING: Routine endoscopy and pathology data from 17 UK hospitals (n = 11,944), and a screening data set comprising three pooled cohorts (n = 2352), followed up using cancer registries. SUBJECTS: Patients with IR adenoma(s) (three or four small adenomas or one or two large adenomas). PRIMARY OUTCOMES: Advanced adenoma (AA) and CRC detected at follow-up visits, and CRC incidence after baseline and first follow-up. METHODS: The effects of surveillance on long-term CRC incidence and of interval length on findings at follow-up were examined using proportional hazards and logistic regression, adjusting for patient, procedural and polyp characteristics. Lower-intermediate-risk (LIR) subgroups and higher-intermediate-risk (HIR) subgroups were defined, based on predictors of CRC risk. A model-based cost-utility analysis compared 13 surveillance strategies. Between-group analyses of variance were used to test for differences in bowel cancer worry between screening outcome groups (n = 35,700). A limitation of using routine hospital data is the potential for missed examinations and underestimation of the effect of interval and surveillance. RESULTS: In the hospital data set, 168 CRCs occurred during 81,442 person-years (pys) of follow-up [206 per 100,000 pys, 95% confidence interval (CI) 177 to 240 pys]. One surveillance significantly lowered CRC incidence, both overall [hazard ratio (HR) 0.51, 95% CI 0.34 to 0.77] and in the HIR subgroup (n = 9265; HR 0.50, 95% CI 0.34 to 0.76). In the LIR subgroup (n = 2679) the benefit of surveillance was less clear (HR 0.62, 95% CI 0.16 to 2.43). Additional surveillance lowered CRC risk in the HIR subgroup by a further 15% (HR 0.36, 95% CI 0.20 to 0.62). The odds of detecting AA and CRC at first follow-up (FUV1) increased by 18% [odds ratio (OR) 1.18, 95% CI 1.12 to 1.24] and 32% (OR 1.32, 95% CI 1.20 to 1.46) per year increase in interval, respectively, and the odds of advanced neoplasia at second follow-up increased by 22% (OR 1.22, 95% CI 1.09 to 1.36), after adjustment. Detection rates of AA and CRC remained below 10% and 1%, respectively, with intervals to 3 years. In the screening data set, 32 CRCs occurred during 25,745 pys of follow-up (124 per 100,000 pys, 95% CI 88 to 176 pys). One follow-up conferred a significant 73% reduction in CRC incidence (HR 0.27, 95% CI 0.10 to 0.71). Owing to the small number of end points in this data set, no other outcome was significant. Although post-screening bowel cancer worry was higher in people who were offered surveillance, worry was due to polyp detection rather than surveillance. The economic evaluation, using data from the hospital data set, suggested that 3-yearly colonoscopic surveillance without an age cut-off would produce the greatest health gain. CONCLUSIONS: A single surveillance benefited all IR patients by lowering their CRC risk. We identified a higher-risk subgroup that benefited from further surveillance, and a lower-risk subgroup that may require only one follow-up. A surveillance interval of 3 years seems suitable for most IR patients. These findings should be validated in other studies to confirm whether or not one surveillance visit provides adequate protection for the lower-risk subgroup of intermediate-risk patients. STUDY REGISTRATION: Current Controlled Trials ISRCTN15213649. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Adenoma surveillance and colorectal cancer incidence: a retrospective, multicentre, cohort study.

BACKGROUND: Removal of adenomas reduces colorectal cancer incidence and mortality; however, the benefit of surveillance colonoscopy on colorectal cancer risk remains unclear. We examined heterogeneity in colorectal cancer incidence in intermediate-risk patients and the effect of surveillance on colorectal cancer incidence. METHODS: We did this retrospective, multicentre, cohort study using routine lower gastrointestinal endoscopy and pathology data from patients who, after baseline colonoscopy and polypectomy, were diagnosed with intermediate-risk adenomas mostly (>99%) between Jan 1, 1990, and Dec 31, 2010, at 17 hospitals in the UK. These patients are currently offered surveillance colonoscopy at intervals of 3 years. Patients were followed up through to Dec 31, 2014.We assessed the effect of surveillance on colorectal cancer incidence using Cox regression with adjustment for patient, procedural, and polyp characteristics. We defined lower-risk and higher-risk subgroups on the basis of polyp and procedural characteristics identified as colorectal cancer risk factors. We estimated colorectal cancer incidence and standardised incidence ratios (SIRs) using as standard the general population of England in 2007. This trial is registered, number ISRCTN15213649. FINDINGS: 253 798 patients who underwent colonic endoscopy were identified, of whom 11 944 with intermediate-risk adenomas were included in this analysis. After a median follow-up of 7·9 years (IQR 5·6-11·1), 210 colorectal cancers were diagnosed. 5019 (42%) patients did not attend surveillance and 6925 (58%) attended one or more surveillance visits. Compared to no surveillance, one or two surveillance visits were associated with a significant reduction in colorectal cancer incidence rate (adjusted hazard ratio 0·57, 95% CI 0·40-0·80 for one visit; 0·51, 0·31-0·84 for two visits). Without surveillance, colorectal cancer incidence in patients with a suboptimal quality colonoscopy, proximal polyps, or a high-grade or large adenoma (≥20 mm) at baseline (8865 [74%] patients) was significantly higher than in the general population (SIR 1·30, 95% CI 1·06-1·57). By contrast, in patients without these features, colorectal cancer incidence was lower than that of the general population (SIR 0·51, 95% CI 0·29-0·84). INTERPRETATION: Colonoscopy surveillance benefits most patients with intermediate-risk adenomas. However, some patients are already at low risk after baseline colonoscopy and the value of surveillance for them is unclear. FUNDING: National Institute for Health Research Health Technology Assessment, Cancer Research UK.

British Society of Gastroenterology position statement on serrated polyps in the colon and rectum.

Serrated polyps have been recognised in the last decade as important premalignant lesions accounting for between 15% and 30% of colorectal cancers. There is therefore a clinical need for guidance on how to manage these lesions; however, the evidence base is limited. A working group was commission by the British Society of Gastroenterology (BSG) Endoscopy section to review the available evidence and develop a position statement to provide clinical guidance until the evidence becomes available to support a formal guideline. The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations-serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions. Statements on these issues were proposed where the evidence was deemed sufficient, and re-evaluated modified via a Delphi process until >80% agreement was reached. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool was used to assess the strength of evidence and strength of recommendation for finalised statements. Key recommendation: we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years (weak recommendation, low quality evidence, 90% agreement).

Long term effects of once-only flexible sigmoidoscopy screening after 17 years of follow-up: the UK Flexible Sigmoidoscopy Screening randomised controlled trial.

BACKGROUND: Colorectal cancer is the third most common cancer worldwide. Previous analyses have only reported follow-up after flexible sigmoidoscopy for a maximum of 12 years. We aimed to examine colorectal cancer incidence and mortality after a single flexible sigmoidoscopy screening and 17 years of follow-up. METHODS: In this multicentre randomised trial (UK Flexible Sigmoidoscopy Screening Trial), done between Nov 14, 1994, and March 30, 1999, 170 432 eligible men and women, who had indicated on a previous questionnaire that they would probably attend screening if invited, were randomly assigned (1:2) to an intervention group (offered flexible sigmoidoscopy screening) or a control group (not contacted). Randomisation was done centrally in blocks of 12, and stratified by trial centre, general practice, and household type. The nature of the intervention did not allow the staff to be masked to arm of the trial; however, randomisation was done in batches so that the control group and participants not yet randomised were unaware of their allocation status. The primary outcomes were incidence and mortality of colorectal cancer. Hazard ratios (HRs) and 95% CIs for colorectal cancer incidence and mortality were estimated for intention-to-treat and per-protocol analyses. The trial is registered with ISRCTN, number 28352761. FINDINGS: Our cohort analysis included 170 034 people: 112 936 in the control group and 57 098 in the intervention group, 40 621 (71%) of whom were screened and 16 477 (29%) were not screened. During screening and a median of 17·1 years' follow-up, colorectal cancer was diagnosed in 1230 individuals in the intervention group and 3253 in the control group, and 353 individuals in the intervention group versus 996 individuals in the control group died from colorectal cancer. In intention-to-treat analyses, colorectal cancer incidence was reduced by 26% (HR 0·74 [95% CI 0·70-0·80]; p<0·0001) in the intervention group versus the control group and colorectal cancer mortality was reduced by 30% (0·70 [0·62-0·79]; p<0·0001) in the intervention group versus the control group. In per-protocol analyses, adjusted for non-compliance, colorectal cancer incidence and mortality were 35% (HR 0·65 [95% CI 0·59-0·71]) and 41% (0·59 [0·49-0·70]) lower in the screened group. INTERPRETATION: A single flexible sigmoidoscopy continues to provide substantial protection from colorectal cancer diagnosis and death, with protection lasting at least 17 years. FUNDING: National Institute for Health Research Efficacy and Mechanism Evaluation.

A national cluster-randomised controlled trial to examine the effect of enhanced reminders on the socioeconomic gradient in uptake in bowel cancer screening.

BACKGROUND: The NHS Bowel Cancer Screening Programme in England offers biennial guaiac faecal occult blood testing (gFOBt). There is a socioeconomic gradient in participation and socioeconomically disadvantaged groups have worse colorectal cancer survival than more advantaged groups. We compared the effectiveness and cost of an enhanced reminder letter with the usual reminder letter on overall uptake of gFOBt and the socioeconomic gradient in uptake. METHODS: We enhanced the usual reminder by including a heading 'A reminder to you' and a short paragraph restating the offer of screening in simple language. We undertook a cluster-randomised trial of all 168 480 individuals who were due to receive a reminder over 20 days in 2013. Randomisation was based on the day of invitation. Blinding of individuals was not possible, but the possibility of bias was minimal owing to the lack of direct contact with participants. The enhanced reminder was sent to 78 067 individuals and 90 413 received the usual reminder. The primary outcome was the proportion of people adequately screened and its variation by quintile of Index of Multiple Deprivation. Data were analysed by logistic regression with conservative variance estimates to take account of cluster randomisation. RESULTS: There was a small but statistically significant (P=0.001) increase in participation with the enhanced reminder (25.8% vs 25.1%). There was significant (P=0.005) heterogeneity of the effect by socioeconomic status with an 11% increase in the odds of participation in the most deprived quintile (from 13.3 to 14.1%) and no increase in the least deprived. We estimated that implementing the enhanced reminder nationally could result in up to 80 more people with high or intermediate risk colorectal adenomas and up to 30 more cancers detected each year if it were implemented nationally. The intervention incurred a small one-off cost of £78 000 to modify the reminder letter. CONCLUSIONS: The enhanced reminder increases overall uptake and reduces the socioeconomic gradient in bowel cancer screening participation at little additional cost.

Using a hypothetical scenario to assess public preferences for colorectal surveillance following screening-detected, intermediate-risk adenomas: annual home-based stool test vs. triennial colonoscopy.

BACKGROUND: To assess public preferences for colorectal cancer (CRC) surveillance tests for intermediate-risk adenomas, using a hypothetical scenario. METHODS: Adults aged 45-54 years without CRC were identified from three General Practices in England (two in Cumbria, one in London). A postal survey was carried out during a separate study on preferences for different first-line CRC screening modalities (non- or full-laxative computed tomographic colonography, flexible sigmoidoscopy, or colonoscopy). Individuals were allocated at random to receive a pack containing information on one first-line test, and a paragraph describing CRC surveillance recommendations for people who are diagnosed with intermediate-risk adenomas during screening. All participants received a description of two surveillance options: annual single-sample, home-based stool testing (consistent with Faecal Immunochemical Tests; FIT) or triennial colonoscopy. Invitees were asked to imagine they had been diagnosed with intermediate-risk adenomas, and then complete a questionnaire on their surveillance preferences. RESULTS: 22.1 % (686/3,100) questionnaires were returned. 491 (15.8 %) were eligible for analysis. The majority of participants stated a surveillance preference for the stool test over colonoscopy (60.8 % vs 31.0 %; no preference: 8.1 %; no surveillance: 0.2 %). Women were more likely to prefer the stool test than men (66.7 % vs. 53.6 %; p = .011). The primary reason for preferring the stool test was that it would be done more frequently. The main reason to prefer colonoscopy was its superiority at finding polyps. CONCLUSIONS: A majority of participants stated a preference for a surveillance test resembling FIT over colonoscopy. Future research should test whether this translates to greater adherence in a real surveillance setting. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry, ISRCTN85697880 , prospectively registered on 25/04/2013.

Recommendations From the International Colorectal Cancer Screening Network on the Evaluation of the Cost of Screening Programs.

Worldwide, colorectal cancer is the fourth leading cause of death from cancer and the incidence is projected to increase. Many countries are exploring the introduction of organized screening programs, but there is limited information on the resources required and guidance for cost-effective implementation. To facilitate the generating of the economics evidence base for program implementation, we collected and analyzed detailed program cost data from 5 European members of the International Colorectal Cancer Screening Network. The cost per person screened estimates, often used to compare across programs as an overall measure, varied significantly across the programs. In addition, there were substantial differences in the programmatic and clinical cost incurred, even when the same type of screening test was used. Based on these findings, several recommendations are provided to enhance the underlying methodology and validity of the comparative economic assessments. The recommendations include the need for detailed activity-based cost information, the use of a comprehensive set of effectiveness measures to adequately capture differences between programs, and the incorporation of data from multiple programs in cost-effectiveness models to increase generalizability. Economic evaluation of real-world colorectal cancer-screening programs is essential to derive valuable insights to improve program operations and ensure optimal use of available resources.

Terminal digit preference biases polyp size measurements at endoscopy, computed tomographic colonography, and histopathology.

BACKGROUND AND STUDY AIMS: Terminal digit preference bias for "pleasing" numbers has been described in many areas of medicine. The aim of this study was to determine whether endoscopists, radiologists, and pathologists exhibit such bias when measuring colorectal polyp diameters. METHODS: Colorectal polyp diameters measured at endoscopy, computed tomographic colonography (CTC), and histopathology were collated from a colorectal cancer screening program and two parallel multicenter randomized trials. Smoothing models were fitted to the data to estimate the expected number of polyps at 1-mm increments, assuming no systematic measurement bias. The difference between the expected and observed numbers of polyps was calculated for each terminal digit using statistical modeling. The impact of measurement bias on per-patient detection rates of polyps ≥ 10 mm was estimated for each modality. RESULTS: A total of 92 124 individual polyps were measured by endoscopy (91 670 screening and 454 from trials), 2385 polyps were measured by CTC (1664 screening, 721 trials), and 79 272 were measured by histopathology (78 783 screening, 489 trials). Clustering of polyp diameter measurements at 5-mm intervals was demonstrated for all modalities, both in the screening program and the trials. The statistical models estimated that per-patient detection rates of polyps ≥ 10 mm were over-inflated by 2.4 % for endoscopy, 3.1 % for CTC, and 3.3 % for histopathology in the screening program, with similar trends in the randomized trials. CONCLUSION: Endoscopists, radiologists, and pathologists all exhibit terminal digit preference when measuring colorectal polyps. This will bias trial data, referral rates for further testing, adenoma surveillance regimens, and comparisons between tests.

Appearances of screen-detected versus symptomatic colorectal cancers at CT colonography.

OBJECTIVES: The aim of this study was to compare the morphology, radiological stage, conspicuity, and computer-assisted detection (CAD) characteristics of colorectal cancers (CRC) detected by computed tomographic colonography (CTC) in screening and symptomatic populations. METHODS: Two radiologists independently analyzed CTC images from 133 patients diagnosed with CRC in (a) two randomized trials of symptomatic patients (35 patients with 36 tumours) and (b) a screening program using fecal occult blood testing (FOBt; 98 patients with 100 tumours), measuring tumour length, volume, morphology, radiological stage, and subjective conspicuity. A commercial CAD package was applied to both datasets. We compared CTC characteristics between screening and symptomatic populations with multivariable regression. RESULTS: Screen-detected CRC were significantly smaller (mean 3.0 vs 4.3 cm, p < 0.001), of lower volume (median 9.1 vs 23.2 cm3, p < 0.001) and more frequently polypoid (34/100, 34 % vs. 5/36, 13.9 %, p = 0.02) than symptomatic CRC. They were of earlier stage than symptomatic tumours (OR = 0.17, 95 %CI 0.07-0.41, p < 0.001), and were judged as significantly less conspicuous (mean conspicuity 54.1/100 vs. 72.8/100, p < 0.001). CAD detection was significantly lower for screen-detected (77.4 %; 95 %CI 67.9-84.7 %) than symptomatic CRC (96.9 %; 95 %CI 83.8-99.4 %, p = 0.02). CONCLUSIONS: Screen-detected CRC are significantly smaller, more frequently polypoid, subjectively less conspicuous, and less likely to be identified by CAD than those in symptomatic patients. KEY POINTS: • Screen-detected colorectal cancers (CRC) are significantly smaller than symptomatic CRC. • Screening cases are significantly less conspicuous to radiologists than symptomatic tumours. • Screen-detected CRC have different morphology compared to symptomatic tumours (more polypoid, fewer annular). • A commercial computer-aided detection (CAD) system was significantly less likely to note screen-detected CRC.

Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial.

Objective. To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake. Participants. 150,417 adults (59-74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013. Design. A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI + N). Between group comparisons were made for uptake overall and across socioeconomic status (SES). Results. Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI + N: 56.7%; odds ratio = 0.93; 95% confidence interval: 0.81-1.06; p = 0.27). There was no interaction between group and SES quintile (p = 0.44). Conclusions. Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace, existing information may have limited the true value of an evidence-based intervention on behaviour.