Interval cancer audit and disclosure in cervical screening programmes: An international survey

Background Legal cases involving the National Cervical Screening Programme in Ireland following non-disclosure of an interval cervical cancer audit prompted this first international comparative survey of interval cervical cancer audit. Methods A survey of 22 international population-based cervical screening programmes was conducted, to determine if they undertook audit of invasive cervical cancers. Those countries/regions that perform reviews were asked (i) how the audit was undertaken, including how the reviews were performed and how they controlled for retrospective bias, (ii) how women are informed of the audit process and how their consent is obtained, and (iii) how audit results were disclosed to patients. Results Seventeen countries/regions invited completed the survey (77%); 65% (11/17) have an audit process for interval cervical cancers. Five perform individual patient reviews; three perform programme-wide review, with calculation of interval cancer detection rates; one routinely performs programme-wide review with calculation of interval cancer detection rates and offers individual reviews, and one routinely performs local hospital-level reviews. In the remaining country/region, hospital laboratories audit cancers, with a national audit process for all cervical cancers. Varying methodologies for retrospective cytology review were employed; four include control samples, with a ratio varying from 1:1 to 1:2. Three conduct a blinded review. Most countries/regions do not discuss interval cancer audit with participants and 3/11 (27.3%) inform women when a cervical cancer audit takes place. Disclosure is limited and variable. Conclusion The responses suggest that there is no consistent approach to audit of interval cervical cancers or to disclosure of audit results.

The impact of cumulative colorectal cancer screening delays: A simulation study

Objective Annual fecal immunochemical tests can reduce colorectal cancer incidence and mortality. However, screening is a multi-step process and most patients do not perfectly adhere to guideline-recommended screening schedules. Our objective was to compare the reduction in colorectal cancer incidence and life-years gained based on US guideline-concordant fecal immunochemical test screening to scenarios with a range of delays. Method The Colorectal Cancer Simulated Population model for Incidence and Natural history (CRC-SPIN) microsimulation model was used to estimate the effect of systematic departures from fecal immunochemical test screening guidelines on lifetime screening benefit. Results The combined effect of consistent modest delays in screening initiation (1 year), repeated fecal immunochemical test screening (3 months), and receipt of follow-up or surveillance colonoscopy (3 months) resulted in up to 1.3 additional colorectal cancer cases per 10,000, 0.4 additional late-stage colorectal cancer cases per 10,000 and 154.7 fewer life-years gained per 10,000. A 5-year delay in screening initiation had a larger impact on screening effectiveness than consistent small delays in repeated fecal immunochemical test screening or receipt of follow-up colonoscopy after an abnormal fecal immunochemical test. The combined effect of consistent large delays in screening initiation (5 years), repeated fecal immunochemical test screening (6 months), and receipt of follow-up or surveillance colonoscopy (6 months) resulted in up to 3.7 additional colorectal cancer cases per 10,000, 1.5 additional late-stage colorectal cancer cases per 10,000 and 612.3 fewer life-years gained per 10,000. Conclusions Systematic delays across the screening process can result in meaningful reductions in colorectal cancer screening effectiveness, especially for longer delays. Screening delays could drive differences in colorectal cancer incidence across patient groups with differential access to screening.

Colonoscopy may be weak link in organised colorectal cancer screening programme with faecal immunochemical test

Objective To evaluate the quality of colonoscopies performed after a positive faecal immunochemical test in the French colorectal cancer screening programme. Methods Retrospective analysis of all colonoscopies performed between 2015 and 2019 after a positive quantitative faecal immunochemical test in the population-based colorectal cancer screening programme organised in Alsace, part of the French programme. The following indicators were evaluated: annual colonoscopy volume, caecal intubation rate, adenoma detection rate, proximal serrated lesion detection rate and proportion of patients referred directly to surgery for benign polyp management. Endoscopists who performed <30 faecal immunochemical test positive colonoscopies were non-assessable. Results Overall, 13,455 faecal immunochemical test-positive colonoscopies performed by 116 community gastroenterologists were included, 13,067 of them by 80 assessable endoscopists. The overall caecal intubation, adenoma detection and proximal serrated lesion detection rates were 97.9%, 57.6% and 7.6%, respectively. They were <90%, <45% and <1% for 1.3%, 12.5% and 6.3% of the endoscopists, respectively. Overall, 1028 (7.9%) individuals were examined by 13 low-performing endoscopists and 328 (2.4%) individuals by 33 low-volume non-assessable endoscopists. Among 9133 individuals harbouring polyps, 155 (1.7%) had unwarranted surgery for a benign polyp. Overall, 1487 individuals (11.1%; 95% confidence interval 10.5–11.6) were not given the best possible chances, whereas 5545 individuals (41.2%; 95% confidence interval 40.4–42.0) were offered the best possible chances by 37 endoscopists. Conclusions At programme level, the key performance indicators evaluated largely exceeded the target standards. At individual level, at least one in nine individuals was not given the best possible chances during faecal immunochemical test-positive colonoscopies by a minority of poor-performing and/or low-volume endoscopists.

Prioritisation of colonoscopy services in colorectal cancer screening programmes to minimise impact of COVID-19 pandemic on predicted cancer burden: A comparative modelling study

Objectives Colorectal cancer (CRC) screening with a faecal immunochemical test (FIT) has been disrupted in many countries during the COVID-19 pandemic. Performing catch-up of missed screens while maintaining regular screening services requires additional colonoscopy capacity that may not be available. This study aimed to compare strategies that clear the screening backlog using limited colonoscopy resources. Methods A range of strategies were simulated using four country-specific CRC natural-history models: Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) and MIcrosimulation SCreening ANalysis for CRC (MISCAN-Colon) (both in the Netherlands), Policy1-Bowel (Australia) and OncoSim (Canada). Strategies assumed a 3-month screening disruption with varying recovery period lengths (6, 12, and 24 months) and varying FIT thresholds for diagnostic colonoscopy. Increasing the FIT threshold reduces the number of referrals to diagnostic colonoscopy. Outcomes for each strategy were colonoscopy demand and excess CRC-related deaths due to the disruption. Results Performing catch-up using the regular FIT threshold in 6, 12 and 24 months could prevent most excess CRC-related deaths, but required 50%, 25% and 12.5% additional colonoscopy demand, respectively. Without exceeding usual colonoscopy demand, up to 60% of excess CRC-related deaths can be prevented by increasing the FIT threshold for 12 or 24 months. Large increases in FIT threshold could lead to additional deaths rather than preventing them. Conclusions Clearing the screening backlog in 24 months could avert most excess CRC-related deaths due to a 3-month disruption but would require a small increase in colonoscopy demand. Increasing the FIT threshold slightly over 24 months could ease the pressure on colonoscopy resources.

All-cause mortality as the primary endpoint for the GRAIL/National Health Service England multi-cancer screening trial

A randomized trial of the GRAIL GalleriTM multi-cancer screening test is being planned for the National Health Service in England, and will have 140,000 healthy participants aged 50–79: 70,000 exposed to screening and 70,000 unexposed. The test reportedly detects 50 different cancers and is expected to reduce all-cancer mortality by approximately 25%. Given this effect size—and that cancer deaths constitute a large fraction of all deaths—the trial is sufficiently large to test the effect on all-cause mortality. Because most patients believe cancer screening “saves lives”, the GRAIL/National Health Service collaboration could set the evaluation standard for multi-cancer screening.

The randomized trial of mammography screening that was not—A cautionary tale

Two randomized trials were conducted in Canada in the 1980s to test the efficacy of breast cancer screening. Neither of the trials demonstrated benefit. Concerns were raised regarding serious errors in trial design and conduct. Here we describe the conditions that could allow subversion of randomization to occur and the inclusion of many symptomatic women in a screening trial. We examine anomalies in data where the balance would be expected between trial arms. “Open book” randomization and performance of clinical breast examination on all women before allocation to a trial arm allowed women with palpable findings to be mis-randomized into the mammography arm. Multiple indicators raising suspicion of subversion are present including a large excess in poor-prognosis cancers in the mammography trial arm at prevalence screen. Personnel described shifting of women from the control group into the mammography group. There is compelling evidence of subversion of randomization in Canadian National Breast Screening Study. Mis-randomization of even a few women with advanced breast cancer could markedly affect measured screening efficacy. The Canadian National Breast Screening Study trials should not influence breast screening policies.

Faecal haemoglobin concentrations in women and men diagnosed with colorectal cancer in a national screening programme

Objective There is evidence that colorectal cancer screening using faecal haemoglobin is less effective in women than men. The faecal haemoglobin concentrations were therefore examined in women and men with screen-detected colorectal cancer. Setting Scottish Bowel Screening Programme, following the introduction of a faecal immunochemical test from November 2017, to March 2020. Methods Data were collated on faecal haemoglobin concentrations, pathological stage and anatomical site of the main lesion in participants who had colorectal cancer detected. The data in women and men were compared. Results For the faecal haemoglobin concentrations studied (>80 µg Hb/g faeces), the distributions indicated lower concentrations in women. Marked differences were found between women and men diagnosed with colorectal cancer. The median faecal haemoglobin concentration for women ( n = 720) was 408 µg Hb/g faeces compared to 473 µg Hb/g faeces for men ( n = 959) ( p = 0.004) and 50.6% of the results were >400 µg Hb/g faeces in women; in men, this was 57.8%. The difference in faecal haemoglobin concentrations in women and men became less statistically significant as stage advanced from stages I–IV. For right-sided, left-sided and rectal colorectal cancer, a similar gender difference persisted in all sites. Differences in faecal haemoglobin between the genders were significant for left-sided cancers and stage I and approached significance for rectal cancers and stage II, but all sites and stages showed lower median faecal haemoglobin concentrations for women. Conclusions To minimise gender inequalities, faecal immunochemical test-based colorectal cancer screening programmes should evaluate a strategy of using different faecal haemoglobin concentration thresholds in women and men.