Kate Wooldrage

Objectives: Colorectal cancer screening with flexible sigmoidoscopy focuses on the distal colorectum, but it is unclear which distal polyp characteristics are associated with future proximal colon cancer incidence. We examined associations between distal adenoma or hyperplastic polyp characteristics and long-term incident proximal colon cancer. Methods: In secondary, observational analyses of UK Flexible Sigmoidoscopy Screening Trial data, we obtained data on the number and size of distal hyperplastic polyps (n=4872) and adenomas (n=4581), adenoma histology and dysplasia from endoscopy and pathology reports for screened asymptomatic participants. Adjusted HRs and 95% CIs for the association between distal polyp characteristics and proximal colon cancer incidence were estimated using multivariable Cox proportional hazard models. Results: Over a median of 20.7 years of follow-up (IQR 16.5–21.7), 110 proximal colon cancers were diagnosed among participants with distal adenomas and 96 were diagnosed among those with only distal hyperplastic polyps detected at baseline. Larger adenoma size (6–9 mm vs ≤5 mm: HR 1.67 (95%CI: 1.07 to 2.59) and ≥10 mm vs ≤5 mm: HR 2.08 (95%CI: 0.98 to 4.43); p=0.037) and high-grade (vs low-grade) adenoma dysplasia (HR 2.82, 95% CI: 1.34 to 5.93; p=0.012) at baseline were positively associated with proximal colon cancer incidence. No associations were observed for distal adenoma number overall or histology, or the number or size of hyperplastic polyps and proximal colon cancer incidence. Conclusions: We found some evidence that larger distal adenomas and those with high-grade dysplasia at baseline were positively associated with proximal colon cancer incidence. Larger studies are needed to confirm these findings. Trial registration number: ISRCTN28352761 .

Background Recommendations for the first postpolypectomy surveillance colonoscopy (SC1), based on stratifying postpolypectomy colorectal cancer (CRC) risk, are well established. Limited data inform recommendations for surveillance beyond SC1. Objective We investigated which patient groups need surveillance beyond SC1. Design Retrospective analysis of patients who underwent colonoscopy with polypectomy at 17 UK hospitals, mostly from 2000 to 2010, and had ≥1 surveillance colonoscopies. Cancer and death data were collected through 2017. We examined patients in groups defined by risk at baseline and SC1, applying risk definitions from the 2020 UK postpolypectomy surveillance guidelines: ‘low risk, low risk’ (LR-LR), ‘high risk, low risk’ (HR-LR), ‘low risk, high risk’ (LR-HR) and ‘high risk, high risk’ (HR-HR). We examined CRC incidence after SC1, censoring at any second surveillance colonoscopy (SC2), and after SC2 through end of follow-up. We compared incidence with general population incidence using standardised incidence ratios (SIRs). Results Analyses included 10 508 patients: LR-LR=6587 (63%), HR-LR=3272 (31%), LR-HR=248 (2%) and HR-HR=401 (4%). Median follow-up from SC1 was 8.0 years and 151 CRCs were diagnosed. Compared with the general population, CRC incidence after SC1 was lower in the LR-LR group (SIR 0.48, 95% CI 0.34 to 0.67), non-significantly different in the HR-LR (SIR 1.17, 0.85 to 1.58) or LR-HR (SIR 2.51, 0.81 to 5.85) groups, but higher in the HR-HR group (SIR 2.84, 1.30 to 5.39). After SC2, CRC incidence in the HR-HR group was no longer higher than in the general population (SIR 1.86, 0.89 to 3.42). Conclusion Patients with high-risk findings at both baseline and SC1 needed an SC2, while those with low-risk findings at SC1 did not, regardless of their baseline findings.

Objective: Colorectal cancer (CRC) screening enables resection of polyp precursor lesions, preventing cancer or detecting it earlier. Post-polypectomy, people can remain at increased CRC risk, prompting surveillance colonoscopy. Less invasive faecal immunochemical tests (FIT) could reduce the burden of surveillance colonoscopy. We investigated whether changes in FIT values over multiple rounds were associated with advanced colorectal neoplasia (ACN) detection. Methods: A cohort of men and women aged 60–72 years deemed intermediate risk by the 2002 UK adenoma surveillance guidelines and scheduled for three yearly colonoscopies were recruited (January 2012–December 2013) within the English Bowel Cancer Screening Programme and offered a quantitative FIT at 1, 2 and 3 years post-baseline colonoscopy for a prospective analysis within a diagnostic accuracy study. Participants positive (≥40 µg haemoglobin/g faeces) at 1 year or 2 years were offered early colonoscopy and excluded, otherwise, colonoscopy was offered at 3 years. Only those who completed three FIT rounds and attended the 3-year colonoscopy were included. Participants were grouped based on changes between FIT rounds, with changes defined as absolute differences ≥4 µg/g, and positivity at round 3. Results: Among 4412 participants, the largest group (n=2773) was the no change category, which had the lowest ACN detection rate (4.7%, 95% CI: 3.9 to 5.5). The serial increase group with a positive round 3 value (n=46) had the highest ACN detection rate (32.6%, 95% CI: 19.5 to 48.0). Conclusion: No change in FIT result across multiple rounds was associated with a low ACN detection rate, while a serial increase was associated with higher ACN detection rates. Further research should consider if sequential rounds of FIT could be used for stratifying individual risk.

Objectives: Colonoscopy surveillance is often performed in post-polypectomy cohorts, likely altering colorectal cancer (CRC) outcomes, but this is often not addressed in CRC incidence analyses. We examined CRC incidence post-endoscopic screening, accounting for surveillance. Methods: We examined UK Flexible Sigmoidoscopy Screening Trial participants who had no, low-risk, or high-risk (≥10 mm, ≥3 adenomas, adenomas with villous features/high-grade dysplasia) distal polyps at screening. Participants with high-risk polyps had an index colonoscopy and 81% had ≥1 surveillance colonoscopies post-screening; <1% of those with no/low-risk polyps had an index or surveillance colonoscopy. We examined CRC incidence over 21 years by anatomic subsite and sex. Standardised incidence ratios (SIRs) compared incidence to general population incidence. Results: Of 39,417 participants, 29,792 (76%), 8162 (21%), and 1463 (4%) had no, low-risk, and high-risk polyps, respectively. In the high-risk group, all-site CRC incidence was non-significantly different from that in the general population, when including all participants, just those who attended surveillance, or just those who did not attend surveillance (SIRs: 0.81 [95% confidence interval: 0.60–1.07]; 0.75 [0.54–1.03]; 1.12 [0.56–2.01], respectively). Without surveillance, compared to the general population, distal cancer incidence was lower among women and men without polyps (SIRs: 0.30 [0.24–0.37]; 0.24 [0.20–0.29], respectively) and women and men with low-risk polyps (SIRs: 0.52 [0.34–0.76]; 0.27 [0.19–0.37], respectively); proximal cancer incidence was lower among men without polyps (SIR: 0.75 [0.64–0.88]), non-significantly different among women without polyps (SIR: 1.07 [0.93–1.22]) and men with low-risk polyps (SIR: 1.22 [0.98–1.51]), but higher among women with low-risk polyps (SIR: 2.22 [1.77–2.76]). Conclusions: Women with low-risk distal polyps at flexible sigmoidoscopy screening had double the risk of proximal colon cancer, compared to the general population.

Colorectal cancer (CRC) is the third most common cancer worldwide. Population-wide screening has been introduced in many countries to reduce the burden of CRC. Flexible sigmoidoscopy is a recommend... Visual 15-Year Benefits of Sigmoidoscopy Screening for Colorectal Cancer. Colorectal cancer (CRC) is the third most common cancer worldwide. Population-wide screening has been introduced i... Background: The effectiveness of screening for colorectal cancer (CRC) by sex and age in randomized trials is uncertain. Objective: To evaluate the 15-year effect of sigmoidoscopy screening on CRC ...

Introduction A high-quality endoscopic examination is key for the detection and removal of adenomas, precursor lesions to colorectal cancer (CRC). Adenoma detection rates (ADRs) are frequently used to measure endoscopist performance but improving other components of the examination could improve adenoma detection. The aim of this study is to investigate how endoscopist performance at flexible sigmoidoscopy (FS) screening affects distal adenoma detection and long-term distal CRC incidence. Methods Among 34,139 participants who received FS screening by the main endoscopist at one of 13 centres in the UK FS Screening Trial, median follow-up was 17 years. Factors examined included bowel preparation quality, insertion and withdrawal time, segment of bowel reached, family history of CRC, patient pain and ADR. Odds ratios (OR) and 95% confidence intervals (CI) for distal adenoma detection were calculated by logistic regression. Cox regression was used to estimate hazard ratios (HR) for distal CRC incidence. Results The overall ADR was 12% and 168 distal CRCs were diagnosed. In multivariable models, a family history of CRC (yes vs. no, OR 1.41, 95%CI 1.22-1.63), poor bowel preparation quality (OR 2.86, 95%CI 1.25-6.55) and higher insertion and withdrawal times (≥4.00 vs. Conclusions These findings highlight the importance of key aspects of endoscopic examinations that are vital to improve distal adenoma detection.

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. Future work: Studies should examine the clinical effectiveness and cost-effectiveness of post-polypectomy surveillance without prior classification of patients into risk groups. Trial registration: This trial is registered as ISRCTN15213649. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 26. See the NIHR Journals Library website for further project information.

Background: Colorectal cancer (CRC) screening is less effective at reducing cancer incidence in the proximal colon compared to the distal colorectum. We aimed to identify adenoma characteristics associated with proximal colon cancer (PCC). Methods: Endoscopy and pathology data for patients with ≥1 adenoma detected at baseline colonoscopy were obtained from 17 UK hospitals between 2001 and 2010. Multivariable Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for PCC, and, for comparison, distal CRC incidence, by adenoma characteristics. Results: Among 18,431 patients, 152 and 105 developed PCC and distal CRC, respectively, over a median follow-up of 9.8 years. Baseline adenoma characteristics positively associated with PCC incidence included number (≥3 vs. < 3: aHR 2.10, 95% CI: 1.42–3.09), histology (tubulovillous/villous vs. tubular: aHR 1.61, 95% CI: 1.10–2.35) and location (any proximal vs. distal only: aHR 1.70, 95% CI: 1.20–2.42), for which there was borderline evidence of heterogeneity by subsite (p = 0.055). Adenoma dysplasia (high vs. low grade) was associated with distal CRC (aHR 2.42, 95% CI: 1.44–4.04), but not PCC (p-heterogeneity = 0.023). Conclusions: Baseline adenoma number, histology and proximal location were independently associated with PCC and may be important to identify patients at higher risk for post-polypectomy PCC.

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.