Screen-detected and interval colorectal cancers in England: Associations with lifestyle and other factors in women in a large UK prospective cohort.

Faecal occult blood (FOB) - based screening programmes for colorectal cancer detect about half of all cancers. Little is known about individual health behavioural characteristics which may be associated with screen-detected and interval cancers. Electronic linkage between the UK National Health Service Bowel Cancer Screening Programme (BCSP) in England, cancer registration and other national health records, and a large on-going UK cohort, the Million Women Study, provided data on 628,976 women screened using a guaiac-FOB test (gFOBt) between 2006 and 2012. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated by logistic and Cox regression for associations between individual lifestyle factors and risk of colorectal tumours. Among screened women, 766 were diagnosed with screen-detected colorectal cancer registered within 2 years after a positive gFOBt result, and 749 with interval colorectal cancers registered within 2 years after a negative gFOBt result. Current smoking was significantly associated with risk of interval cancer (RR 1.64, 95%CI 1.35-1.99) but not with risk of screen-detected cancer (RR 1.03, 0.84-1.28), and was the only factor of eight examined to show a significant difference in risk between interval and screen-detected cancers (p for difference, 0.003). Compared to screen-detected cancers, interval cancers tended to be sited in the proximal colon or rectum, to be of non-adenocarcinoma morphology, and to be of higher stage.

Factors affecting adenoma detection rate in a national flexible sigmoidoscopy screening programme: a retrospective analysis.

BACKGROUND: A national colorectal cancer screening programme started in England in 2013, offering one-off flexible sigmoidoscopy to all men and women aged 55 years in addition to the biennial faecal occult blood testing programme offered to all individuals aged 60-74 years. We analysed data from six pilot flexible sigmoidoscopy screening centres to examine factors affecting the adenoma detection rate (ADR). METHODS: We did a retrospective analysis of flexible sigmoidoscopy screening procedures performed in individuals aged 55 years at six pilot sites in England as part of the National Health Service Bowel Scope Screening programme. ADR (number of procedures in which at least one adenoma was removed or biopsied, divided by total number of procedures) was calculated for each site and each endoscopist. Multiple regression models were used to examine the variation in ADR with withdrawal time and extent of examination, and the effect of other factors including comfort and bowel preparation on extent of examination. FINDINGS: The analysis included 8256 procedures done between May 7, 2013, and May 6, 2014. The overall ADR was 9·1% (95% CI 8·5-9·8; 755 of 8256 procedures), varying from 7·4% (6·2-8·9) to 11·0% (9·1-13·4) by screening centre. The ADR was 11·5% (95% CI 10·6-12·5; 493 of 4299 procedures) in men and 6·6% (5·9-7·4; 262 of 3957 procedures) in women (p<0·0001). On multivariate analysis, factors associated with adenoma detection were male sex (relative risk 1·69, 95% CI 1·46-1·95; p<0·0001) and a withdrawal time from the splenic flexure of at least 3·25 min in negative procedures (1·22, 1·00-1·48; p=0·045). However, increasing the withdrawal time to 4·0 min or more did not increase the likelihood of adenoma detection (1·22, 0·99-1·51; p=0·057). Procedures not reaching the splenic flexure were associated with lower chance of adenoma detection (eg, 0·77, 0·66-0·91; p=0·0015 for procedures reaching the descending colon), but there was no additional benefit associated with reaching the transverse colon (0·83, 0·67-1·02; p=0·069). Women (0·83, 0·80-0·87; p<0·0001), individuals with adequate (0·79, 0·76-0·83; p<0·0001) or poor (0·58, 0·51-0·67; p<0·0001) bowel preparation (compared with good bowel preparation), and those with mild (0·82, 0·76-0·88; p<0·0001) or moderate or severe (0·58, 0·51-0·66; p<0·0001) discomfort (compared with no discomfort) were less likely to have a procedure reaching the splenic flexure. INTERPRETATION: Key performance indicators for flexible sigmoidoscopy screening should be defined, including standards for insertion and withdrawal times, optimal depth, and bowel preparation. ADR could be improved by recommending a withdrawal time from the splenic flexure of at least 3·25 min (ideally 3·5-4·0 min). FUNDING: None.

Association of ten gastrointestinal and other medical conditions with positivity to faecal occult blood testing in routine screening: a large prospective study of women in England.

BACKGROUND: In 2006, the Bowel Cancer Screening Programme (BCSP) in England began offering biennial faecal occult blood testing (FOBt) at ages 60-69 years. Although FOBt is aimed at detecting colorectal neoplasms, other conditions can affect the result. In a large UK prospective study, we examined associations, both before and after screening, between FOBt positivity and 10 conditions that are often associated with gastrointestinal bleeding. METHODS: By electronically linking BCSP and Million Women Study records, we identified 604 495 women without previous colorectal cancer who participated in their first routine FOBt screening between 2006 and 2012. Regression models, using linked national hospital admission records, yielded adjusted relative risks (RRs) in FOBt-positive versus FOBt-negative women for colorectal cancer, adenoma, diverticular disease, inflammatory bowel disease, haemorrhoids, upper gastrointestinal cancer, oesophagitis, peptic ulcer, anaemia and other haematological disorders. RESULTS: RRs in FOBt-positive versus FOBt-negative women were 201.3 (95% CI 173.8-233.2) for colorectal cancer and 197.9 (95% CI 180.6-216.8) for adenoma within 12 months after screening and 3.49 (95% CI 2.31-5.26) and 4.88 (95% CI 3.80-6.26), respectively, 12-24 months after screening; P < 0.001 for all RRs. In the 12 months after screening, the RR for inflammatory bowel disease was 26.3 (95% CI 19.9-34.7), and ranged between 2 and 5 for the upper gastrointestinal or haematological disorders. The RRs of being diagnosed with any of the eight conditions other than colorectal neoplasms before screening, and in the 12-24 months after screening, were 1.81 (95% CI 1.81-2.01) and 1.92 (95% CI 1.66-2.13), respectively. CONCLUSIONS: Whereas FOBt positivity is associated with a substantially increased risk of colorectal neoplasms after screening, eight other gastrointestinal and haematological conditions are also associated with FOBt positivity, both before and after screening.

Impact of Digital Mammography on Cancer Detection and Recall Rates: 11.3 Million Screening Episodes in the English National Health Service Breast Cancer Screening Program.

Purpose To report the impact of changing from screen-film mammography to digital mammography (DM) in a large organized national screening program. Materials and Methods A retrospective analysis of prospectively collected annual screening data from 2009-2010 to 2015-2016 for the 80 facilities of the English National Health Service Breast Cancer Screening Program, together with estimates of DM usage for three time periods, enabled the effect of DM to be measured in a study of 11.3 million screening episodes in women aged 45-70 years (mean age, 59 years). Regression models were used to estimate percentage and absolute change in detection rates due to DM. Results The overall cancer detection rate was 14% greater with DM (P < .001). There were higher rates of detection of grade 1 and 2 invasive cancers (both ductal and lobular), but no change in the detection of grade 3 invasive cancers. The recall rate was almost unchanged by the introduction of DM. At prevalent (first) screening episodes for women aged 45-52 years, DM increased the overall detection rate by 19% (P < .001) and for incident screening episodes in women aged 53-70 years by 13% (P < .001). Conclusion The overall cancer detection rate was 14% greater with digital mammography with no change in recall rates and without confounding by changes in other factors. There was a substantially higher detection of grade 1 and grade 2 invasive cancers, including both ductal and lobular cancers, but no change in the detection of grade 3 invasive cancers. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by C.I. Lee and J.M. Lee in this issue.

Association between Screening Mammography Recall Rate and Interval Cancers in the UK Breast Cancer Service Screening Program: A Cohort Study.

Purpose To determine whether low levels of recall lead to increased interval cancers and the magnitude of this effect. Materials and Methods The authors retrospectively analyzed prospectively collected data from the UK National Health Service Breast Screening Programme during a 36-month period (April 1, 2005 to March 31, 2008), with 3-year follow-up in women aged 50-70 years. Data on recall, cancers detected at screening, and interval cancers were available for each of the 84 breast screening units and for each year (n = 252). The association between interval cancers and recalls was modeled by using Poisson regression on aggregated data and according to age (5-year intervals) and screening type (prevalent vs incident). Results The authors analyzed 5 126 689 screening episodes, demonstrating an average recall to assessment rate (RAR) of 4.56% (range, 1.64%-8.42%; standard deviation, 1.15%), cancer detection rate of 8.1 per 1000 women screened, and interval cancer rate (ICR) of 3.1 per 1000 women screened. Overall, a significant negative association was found between RAR and ICR (Poisson regression coefficient: -0.039 [95% confidence interval: -0.062, -0.017]; P = .001), with approximately one fewer interval cancer for every additional 80-84 recalls. Subgroup analysis revealed similar negative correlations in women aged 50-54 years (P = .002), 60-64 years (P = .01), and 65-69 years (P = .008) as well as in incident screens (P = .001) and prevalent screens (P = .04). No significant relationship was found in women aged 55-59 years (P = .46). Conclusion There was a statistically significant negative correlation between RAR and ICR, which suggests the merit of a minimum threshold for RAR. © RSNA, 2018 Online supplemental material is available for this article.

Heterogeneity of colorectal cancer risk by tumour characteristics: Large prospective study of UK women.

Associations between behavioural and other personal factors and colorectal cancer risk have been reported to vary by tumour characteristics, but evidence is inconsistent. In a large UK-based prospective study we examined associations of 14 postulated risk factors with colorectal cancer risk overall, and across three anatomical sites and four morphological subtypes. Among 1.3 million women, 18,518 incident colorectal cancers were identified during 13.8 (SD 3.4) years follow-up via record linkage to national cancer registry data. Cox regression yielded adjusted relative risks. Statistical significance was assessed using correction for multiple testing. Overall, colorectal cancer risk was significantly associated with height, body mass index (BMI), smoking, alcohol intake, physical activity, parity and menopausal hormone therapy use. For smoking there was substantial heterogeneity across morphological types; relative risks around two or greater were seen in current smokers both for signet ring cell and for neuroendocrine tumours. Obese women were also at higher risk for signet ring cell tumours. For adenocarcinomas, the large majority of colorectal cancers in the cohort, all risk factor associations were weak. There was little or no heterogeneity in risk between tumours of the right colon, left colon and rectum for any of the 14 factors examined. These epidemiological findings complement an emerging picture from molecular studies of possible different developmental pathways for different tumour types.

Evaluation of colonoscopy performance based on post-procedure bleeding complications: application of procedure complexity-adjusted model.

BACKGROUND AND STUDY AIM: High quality colonoscopy requires low complication rates. However in quality assurance, evaluation of individual colonoscopist complication rates is limited because complications are relatively rare events and there is variation in average procedure complexity. The aim of the study was to develop a quality system that adjusted for procedure complexity to monitor bleeding adverse events at both the screening center and colonoscopist levels. METHODS: The study examined the risk factors for post-procedure bleeding from 130 831 colonoscopies conducted between August 2006 and January 2012. Binomial and logistic regression models were used to examine the risk of events against explanatory variables including age, sex, polyps resected, and polyp size. The models were used to produce a procedure-adjusted standardized adverse event ratio (PASAER) based on the ratio of the observed to expected number of adverse events. The primary outcome of interest was to identify centers that were outside a funnel plot outlier level of 99.8 % (3 SDs). RESULTS: Mulivariate models showed that the risk of bleeding was associated with largest resected polyp size, sex, polyp location, and degree of co-morbidity. These variables were used to calculate PASAERs for the 59 screening centers and 286 colonoscopists. The method highlighted one center with a high PASAER of 3.08 (32 observed compared with 10.4 expected events) and one with a low PASAER of 0.34 (10 observed compared with 29.8 expected events), which merited further investigation. CONCLUSIONS: The PASAER provided additional certainty that a crude adverse event rate was not confounded by procedure complexity, thus objectively identifying centers or colonoscopists that required further performance evaluation.

Colonoscopic factors associated with adenoma detection in a national colorectal cancer screening program.

BACKGROUND AND STUDY AIMS: Adenoma detection is a key objective of colonoscopy, particularly in the context of colorectal cancer screening. The aim of this observational study was to identify the technical colonoscopy factors associated with adenoma detection. PATIENTS AND METHODS: The study analyzed data from the English Bowel Cancer Screening Programme. The indication for all colonoscopies was a positive fecal occult blood test. The relationships between the following colonoscopy factors and adenoma detection (one or more adenomas, advanced adenomas, right-sided adenomas, and total number of adenomas) were examined in multivariable analyses: bowel preparation quality, cecal intubation, withdrawal time, rectal retroversion, colonoscopist experience, antispasmodic use, sedation use, and start time of procedure. The following patient factors were controlled for: age, sex, body mass index, smoking, alcohol, deprivation, and geographical location. RESULTS: A total of 31088 colonoscopies were analyzed. The following technical factors increased the relative risk of adenoma detection (P < 0.001 in multivariable analysis unless otherwise stated): cecal intubation, increased withdrawal time, higher quality bowel preparation, intravenous antispasmodic use, earlier procedure start time within a session (P = 0.018), and greater colonoscopist experience. Detection of advanced and right-sided adenomas also increased with these factors. Adenoma detection did not differ between sedated and unsedated colonoscopy (P = 0.143). CONCLUSION: This study demonstrated important associations between colonoscopy practice and adenoma detection. Use of intravenous antispasmodic was associated with increased adenoma detection. The effect of the start time of colonoscopy suggests that endoscopist fatigue may have a deleterious impact on adenoma detection.

Risk factors for adverse events related to polypectomy in the English Bowel Cancer Screening Programme.

BACKGROUND AND STUDY AIMS: The English National Health Service Bowel Cancer Screening Programme (NHSBCSP) is one of the world's largest organized screening programs. Minimizing adverse events is essential for any screening program. Study aims were to determine rates and to examine risk factors for adverse events. PATIENTS AND METHODS: Bleeding and perforations in NHSBCSP colonoscopies between August 2006 and January 2012 were examined. Logistic regression was used to examine risk factors for adverse events, including age, gender, polyp size, morphology, and location. For accurate attribution of adverse events, procedures with resection of only one polyp ("single-polypectomy") were analyzed in detail. RESULTS: 130 831 colonoscopies (167 208 polypectomies) were analyzed, including 30 881 single-polypectomies. Overall bleeding rate was 0.65 %, rate of bleeding requiring transfusion was 0.04 % and perforation rate was 0.06 %. Polypectomy increased bleeding risk 11.14-fold and perforation risk 2.97-fold. Cecal location (but not elsewhere in the proximal colon) and increasing polyp size were the two most important risk factors for bleeding and perforation. After adjustment for polyp size, the odds ratio (OR) relative to the distal colon for bleeding requiring transfusion after cecal snare polypectomy was 13.5 (95 %CI 3.9 - 46.4) and for perforation after cecal nonpedunculated polypectomy it was 12.2 (95 %CI 1.2 - 119.5). CONCLUSION: This is the largest study focusing on polyp-specific risk factors. We have confirmed that the greatest risk factor for both post-polypectomy bleeding and perforation is polyp size. This is the first demonstration of substantial and significantly increased risk for both noteworthy bleeding (requiring transfusion) and perforation from cecal polypectomy for a given polyp size, compared with elsewhere in the colon.

The calculation of targets for the cancer and adenoma detection rates for the NHS bowel screening programme.

OBJECTIVES: The NHS bowel screening programme offers people aged 60-69 screening by faecal occult blood (FOB) testing, with colonoscopy as the diagnostic test. This paper describes the calculation of targets for the purpose of monitoring screening performance in the programme. METHODS: Targets were calculated for the prevalent round of screening in people aged 60-69, and for the 'steady state' of the programme when people will be offered their first screen at age 60 and subsequent screens at ages 62-69. Targets for the cancer and adenoma detection rates per 1000 people screened and per 100 colonoscopies were calculated using information from the English bowel cancer screening pilot. RESULTS: For the prevalent round, prevalent screen and incident screens the calculated targets for the cancer detection rate are 2.3, 1.3 and 1.7 per 1000 people respectively. For the adenoma detection rate the targets are 6.7, 5.2 and 5.5 per 1000 respectively. Targets for the cancer detection rate per 100 colonoscopies are 11.3, 7.5 and 8.4 and those for the adenoma detection rate are 32.0, 30.4 and 32.5 respectively. CONCLUSIONS: The purpose of these targets is to ensure that the national bowel cancer screening programme is effective with a high quality of screening. The cancer detection and adenoma detection rates per 1000 people are those estimated to be necessary to achieve the expected mortality reduction. Rates per 100 colonoscopies (equivalent to the positive predictive value of referral to colonoscopy) are designed to maintain a high quality of screening by minimizing the number of false-positive referrals.

Colonoscopy quality measures: experience from the NHS Bowel Cancer Screening Programme.

OBJECTIVES: Colonoscopy is central to colorectal cancer (CRC) screening. Success of CRC screening is dependent on colonoscopy quality. The NHS Bowel Cancer Screening Programme (BCSP) offers biennial faecal occult blood (FOB) testing to 60-74 year olds and colonoscopy to those with positive FOB tests. All colonoscopists in the screening programme are required to meet predetermined standards before starting screening and are subject to ongoing quality assurance. In this study, the authors examine the quality of colonoscopy in the NHS BCSP and describe new and established measures to assess and maintain quality. DESIGN: The NHS BCSP database collects detailed data on all screening colonoscopies. Prospectively collected data from the first 3 years of the programme (August 2006 to August 2009) were analysed. Colonoscopy quality indicators (adenoma detection rate (ADR), polyp detection rate, colonoscopy withdrawal time, caecal intubation rate, rectal retroversion rate, polyp retrieval rate, mean sedation doses, patient comfort scores, bowel preparation quality and adverse event incidence) were calculated along with measures of total adenoma detection. RESULTS: 2,269,983 individuals returned FOB tests leading to 36,460 colonoscopies. Mean unadjusted caecal intubation rate was 95.2%, and mean withdrawal time for normal procedures was 9.2 min. The mean ADR per colonoscopist was 46.5%. The mean number of adenomas per procedure (MAP) was 0.91; the mean number of adenomas per positive procedure (MAP+) was 1.94. Perforation occurred after 0.09% of procedures. There were no procedure-related deaths. CONCLUSIONS: The NHS BCSP provides high-quality colonoscopy, as demonstrated by high caecal intubation rate, ADR and comfort scores, and low adverse event rates. Quality is achieved by ensuring BCSP colonoscopists meet a high standard before starting screening and through ongoing quality assurance. Measuring total adenoma detection (MAP and MAP+) as adjuncts to ADR may further enhance quality assurance.

Automation-assisted versus manual reading of cervical cytology (MAVARIC): a randomised controlled trial.

BACKGROUND: The standard for reading cervical cytology is for a cytoscreener to manually search across an entire slide for abnormal cells using a conventional microscope. Automated technology can select fields of view to assess abnormal cells, which allows targeted reading by cytoscreeners. In the Manual Assessment Versus Automated Reading In Cytology (MAVARIC) trial, we compared the accuracy of these techniques for the detection of underlying disease. METHODS: For this randomised controlled trial, women aged 25-64 years undergoing primary cervical screening in Manchester, UK, were randomly assigned (1:2) to receive either manual reading only or paired reading (automation-assisted reading and manual reading), between March 1, 2006, and Feb 28, 2009. In the paired arm, two automated systems were used-the ThinPrep Imaging System and the FocalPoint GS Imaging System. General practices and community clinics were randomised to either ThinPrep or to SurePath (for the FocalPoint system) liquid-based cytology with block randomisation stratified by deprivation index. Samples were then individually randomised to manual reading only or paired reading only. Laboratory staff were unaware of the allocation of each slide and concealment was maintained until the end of the reporting process. The primary outcome was sensitivity of automation-assisted reading relative to manual reading for the detection of underlying cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in the paired arm. This trial is registered, number ISRCTN66377374. FINDINGS: 73,266 liquid-based cytology samples were obtained from women undergoing primary cervical screening; 24,688 allocated to the manual-only arm and 48,578 to the paired-reading arm. Automation-assisted reading was 8% less sensitive than manual reading (relative sensitivity 0·92, 95% CI 0·89-0·95), which was equivalent to an absolute reduction in sensitivity of 6·3%, assuming the sensitivity of manual reading to be 79%. Specificity of automation-assisted reading relative to manual reading increased by 0·6% (1·006, 95% CI 1·005-1·007). INTERPRETATION: The inferior sensitivity of automation-assisted reading for the detection of CIN2+, combined with an inconsequential increase in specificity, suggests that automation-assisted reading cannot be recommended for primary cervical screening.

Comparison of screening mammography in the United States and the United kingdom.

CONTEXT: Screening mammography differs between the United States and the United Kingdom; a direct comparison may suggest methods to improve the practice. OBJECTIVE: To compare screening mammography performance between the United States and the United Kingdom among similar-aged women. DESIGN, SETTING, AND PARTICIPANTS: Women aged 50 years or older were identified who underwent 5.5 million mammograms from January 1, 1996, to December 31, 1999, within 3 large-scale mammography registries or screening programs: the Breast Cancer Surveillance Consortium (BCSC, n = 978 591) and National Breast and Cervical Cancer Early Detection Program (NBCCEDP, n = 613 388) in the United States; and the National Health Service Breast Screening Program (NHSBSP, n = 3.94 million) in the United Kingdom. A total of 27 612 women were diagnosed with breast cancer (invasive or ductal carcinoma in situ) within 12 months of screening among the 3 groups. MAIN OUTCOME MEASURES: Recall rates (recommendation for further evaluation including diagnostic imaging, ultrasound, clinical examination, or biopsy) and cancer detection rates were calculated for first and subsequent mammograms, and within 5-year age groups. RESULTS: Recall rates were approximately twice as high in the United States than in the United Kingdom for all age groups; however, cancer rates were similar. Among women aged 50 to 54 years who underwent a first screening mammogram, 14.4% in the BCSC and 12.5% in the NBCCEDP were recalled for further evaluation vs only 7.6% in the NHSBSP. Cancer detection rates per 1000 mammogram screens were 5.8, 5.9, and 6.3, in the BCSC, NBCCEDP, and NHSBSP, respectively. Recall rates were lower for subsequent examinations in all 3 settings but remained twice as high in the United States. A similar percentage of women underwent biopsy in each setting, but rates of percutaneous biopsy were lower and open surgical biopsy higher in the United States. Open surgical biopsies not resulting in a diagnosis of cancer (negative biopsies) were twice as high in the United States than in the United Kingdom. Based on a 10-year period of screening 1000 women aged 50 to 59 years, 477, 433, and 175 women in the BCSC, NBCCEDP, and NHSBSP, respectively, would be recalled; and for women aged 60 to 69 years, 396, 334, and 133 women, respectively. The estimated cancer detection rates per 1000 women aged 50 to 59 years were 24.5, 23.8, and 19.4, respectively, and for women aged 60 to 69 years, 31.5, 26.6, and 27.9, respectively. CONCLUSIONS: Recall and negative open surgical biopsy rates are twice as high in US settings than in the United Kingdom but cancer detection rates are similar. Efforts to improve US mammographic screening should target lowering the recall rate without reducing the cancer detection rate.