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

Objectives: 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 years 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 (AA), and advanced colorectal neoplasia (ACN: AA/CRC). Results: Uptake of gFOBT at first invite 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=5,532), gFOBT uptake at first invite 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

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 cm(3), 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

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

National Institute for Health Research Efficacy and Mechanism Evaluation

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

Post-polypectomy surveillance interval and advanced neoplasia detection rates: a multicenter, retrospective cohort study

Background Longer post-polypectomy surveillance intervals are associated with increased colorectal neoplasia detection at surveillance in some studies. We investigated this association to inform optimal surveillance intervals. Methods Patients who underwent colonoscopy and post-polypectomy surveillance at 17 UK hospitals were classified as low/high risk by baseline findings. We compared detection rates of advanced adenomas (≥ 10 mm, tubulovillous/villous, high grade dysplasia), high risk findings (HRFs: ≥ 2 serrated polyps/[adenomas] of which ≥ 1 is ≥ 10 mm or has [high grade] dysplasia; ≥ 5 serrated polyps/adenomas; or ≥ 1 nonpedunculated polyp ≥ 20 mm), or colorectal cancer (CRC) at surveillance colonoscopy by surveillance interval (< 18 months, 2, 3, 4, 5, 6 years). Risk ratios (RRs) were estimated using multivariable regression. Results Of 11 214 patients, 7216 (64 %) were low risk and 3998 (36 %) were high risk. Among low risk patients, advanced adenoma, HRF, and CRC detection rates at first surveillance were 7.8 %, 3.7 %, and 1.1 %, respectively. Advanced adenoma detection increased with increasing surveillance interval, reaching 9.8 % with a 6-year interval (P trend < 0.001). Among high risk patients, advanced adenoma, HRF, and CRC detection rates at first surveillance were 15.3 %, 10.0 %, and 1.5 %, respectively. Advanced adenoma and CRC detection rates (P trends < 0.001) increased with increasing surveillance interval; RRs (95 % confidence intervals) for CRC were 1.54 (0.68–3.48), 4.44 (1.95–10.08), and 5.80 (2.51–13.40) with 3-, 4-, and 5-year intervals, respectively, versus an interval of < 18 months. Conclusions Metachronous neoplasia was uncommon among low risk patients, even with long surveillance intervals, supporting recommendations for no surveillance in these patients. For high risk patients, a 3-year surveillance interval would ensure timely CRC detection

Colonoscopy surveillance following adenoma removal to reduce the risk of colorectal cancer: a retrospective cohort study

Background Colonoscopy surveillance is recommended for some patients post polypectomy. The 2002 UK surveillance guidelines classify post-polypectomy patients into low, intermediate and high risk, and recommend different strategies for each classification. Limited evidence supports these guidelines. Objectives To examine, for each risk group, long-term colorectal cancer incidence by baseline characteristics and the number of surveillance visits; the effects of interval length on detection rates of advanced adenomas and colorectal cancer at first surveillance; and the cost-effectiveness of surveillance compared with no surveillance. Design A retrospective cohort study and economic evaluation. Setting Seventeen NHS hospitals. Participants Patients with a colonoscopy and at least one adenoma at baseline. Main outcome measures Long-term colorectal cancer incidence after baseline and detection rates of advanced adenomas and colorectal cancer at first surveillance. Data sources Hospital databases, NHS Digital, the Office for National Statistics, National Services Scotland and Public Health England. Methods Cox regression was used to compare colorectal cancer incidence in the presence and absence of surveillance and to identify colorectal cancer risk factors. Risk factors were used to stratify risk groups into higher- and lower-risk subgroups. We examined detection rates of advanced adenomas and colorectal cancer at first surveillance by interval length. Cost-effectiveness of surveillance compared with no surveillance was evaluated in terms of incremental costs per colorectal cancer prevented and per quality-adjusted life-year gained. Results Our study included 28,972 patients, of whom 14,401 (50%), 11,852 (41%) and 2719 (9%) were classed as low, intermediate and high risk, respectively. The median follow-up time was 9.3 years. Colorectal cancer incidence was 140, 221 and 366 per 100,000 person-years among low-, intermediate- and high-risk patients, respectively. Attendance at one surveillance visit was associated with reduced colorectal cancer incidence among low-, intermediate- and high-risk patients [hazard ratios were 0.56 (95% confidence interval 0.39 to 0.80), 0.59 (95% confidence interval 0.43 to 0.81) and 0.49 (95% confidence interval 0.29 to 0.82), respectively]. Compared with the general population, colorectal cancer incidence without surveillance was similar among low-risk patients and higher among high-risk patients [standardised incidence ratios were 0.86 (95% confidence interval 0.73 to 1.02) and 1.91 (95% confidence interval 1.39 to 2.56), respectively]. For intermediate-risk patients, standardised incidence ratios differed for the lower- (0.70, 95% confidence interval 0.48 to 0.99) and higher-risk (1.46, 95% confidence interval 1.19 to 1.78) subgroups. In each risk group, incremental costs per colorectal cancer prevented and per quality-adjusted life-year gained with surveillance were lower for the higher-risk subgroup than for the lower-risk subgroup. Incremental costs per quality-adjusted life-year gained were lowest for the higher-risk subgroup of high-risk patients at £7821. Limitations The observational design means that we cannot assume that surveillance caused the reductions in cancer incidence. The fact that some cancer staging data were missing places uncertainty on our cost-effectiveness estimates. Conclusions Surveillance was associated with reduced colorectal cancer incidence in all risk groups. However, in low-risk patients and the lower-risk subgroup of intermediate-risk patients, colorectal cancer incidence was no higher than in the general population without surveillance, indicating that surveillance might not be necessary. Surveillance was most cost-effective for the higher-risk subgroup of high-risk patients

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

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 (BCSP) offers biennial screening with a guaiac faecal occult blood test (gFOBT) to 60-74 year olds. Participants with a positive gFOBT are referred for follow-up, but many do not have significant findings. These individuals are reinvited for gFOBT screening provided they remain in the eligible age range. We evaluated the performance of repeat screening in this group. Methods We analysed data on BCSP participants reinvited to gFOBT screening, either after previous negative gFOBT (n=327,542), or after a 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 After a positive gFOBT and a negative diagnostic investigation, gFOBT 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%. For participants with a previous negative gFOBT, in the subsequent screening round uptake 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%. 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 exam needs to be carefully considered