Triage with fecal immunochemical testing (FIT) of symptomatic patients in primary care could streamline access to colonoscopy despite bottlenecks due to the coronavirus pandemic, COVID-19, a U.K. modelling study suggested.
FIT screening would reduce delays for true-positive colorectal (CRC) cases and nosocomial COVID-19 mortality in older true-negative patients in the current 2-week wait (2WW) pathway, reported Clare Turnbull, PhD, of the Institute of Cancer Research at Queen Mary University of London, and colleagues, in Gut.
"Urgent referral of symptomatic patients and bottlenecks in endoscopy have potential to cause high attributable deaths and lost life years. FIT triage at 10 μg Hb/g offers opportunity to mitigate 89% of these deaths and reduce exposure of patients to nosocomial COVID-19 infection," Turnbull and colleagues wrote.
The group estimated that delays of 2, 4, or 6 months across 11,266 patients diagnosed with CRC per typical year via the 2WW pathway would result in 653, 1,419, and 2,250 attributable deaths, respectively. Corresponding losses of life-years would be 9,214, 20,315, and 32,799.
Prioritizing higher-risk patients out of the U.K. National Health Service's standard 2WW delay could not only prevent nearly all those predicted deaths, but the immediate requirement for colonoscopy would decline by more than 80%, the authors concluded.
They noted that the risk–benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients older than 60. As elsewhere, Britain has seen disruptions across cancer diagnostics and surgery, particularly affecting CRC owing to the widespread shutdown of routine endoscopy from safety concerns and understaffing.
Recommendations released this year specified that all symptomatic patients in Britain should undergo FIT testing, with only those with FIT >10µg Hb/g referred into secondary care and those with FIT >150µg Hb/g prioritized for colonoscopy.
The researchers, cautioned, however, that the utility of FIT-based prioritization would be short term in nature and designed to get FIT-positive symptomatic patients out of delay and reduce pressure on endoscopy services. "Given that disruption of cancer services may persist for multiple years due to successive waves of the COVID-19 pandemic, in order to avoid substantial numbers of deaths attributable to pathway delay, urgent attention is required to minimise and mitigate disruption to CRC diagnostics and treatment," Turnbull and colleagues wrote.
Moreover, they pointed out that their analyses were based on a hypothetical, universal per-patient pathway delay lasting an arbitrary 1 year. In reality, delays vary temporally, geographically, and individually, "and the overall duration of disruption has yet to play out."
The study used recent data from national U.K. cancer registries and life tables, also employing current cancer wait data for West London and recent wait-impact survival data from Taiwan to assess delay-related CRC mortality.
Stratified by age group, the authors looked at individual-level benefit in CRC survival versus age-specific nosocomial COVID-19–related fatality per referred patient undergoing colonoscopy.
Mitigation strategies were modelled with thresholds of FIT triage of 2, 10, and 150 μg Hb/g to prioritize 2WW referrals for colonoscopy. Ten-year net CRC survival data for England in 2008-2017, 2WW pathway CRC case and referral volumes, and per-day-delay hazard ratios generated from observational data on diagnosis-to-treatment interval were also used.
Turnbull's group argued that, since CRC diagnosis, management and survival are directly comparable across most economically developed countries, the impact of delay highlighted by the study is broadly applicable.
But while describing the study as "well done, given the limitations of the model," Thomas F. Imperiale, MD, of Indiana School of Medicine in Indianapolis, said the results seem less relevant to the U.S. because of its capacity for colonoscopy even in the COVID-19 era. "The results seem best suited for a setting, country, or healthcare system with comparable population-based CRC incidence and mortality, comparable baseline screening rates, and comparable resources," he told MedPage Today.
"What is not clear to me is how well the specific signs and symptoms alone would have done in selecting patients for earlier diagnostic colonoscopy as opposed to the FIT results," added Imperiale, who was not involved in the study. Presence of rectal bleeding and iron deficiency anemia, he suggested, might have outperformed FIT in identifying patients for whom delaying diagnostic colonoscopy would be harmful.
"It would seem to make sense that FIT would be best used for those patients whose primary symptom or sign is less specific – for example, the symptom of change in bowel habit or the sign of anemia that is not due to iron deficiency," Imperiale said.
Turnbull and colleagues noted that their model's accuracy depends on the validity of its assumptions and the estimates used for parameterization. Furthermore, the only substantial available data on wait/delay impact came from an Asian population.
Additionally, the analysis focused explicitly on survival, whereas a more elaborate model capturing CRC stage transition might better aid healthcare planning. And while most 2WW referrals are typically investigated by colonoscopy, no data were available on the proportion of patients typically diverted in secondary care to alternative investigation such as computed tomography.
As well, the study was also unable to capture the impact of delay on diagnoses of other cancers often found during CRC investigation.
Finally, in focusing on urgent symptomatic patients, the study did not consider other routes to CRC diagnosis such as routine screening or routine endoscopic follow-up.
Last Updated September 01, 2020
Disclosures
This study was supported by the Institute for Cancer Research. Turnbull reported support from the Movember Foundation.
Other authors disclosed support, variously, from the National Institute for Health Research, the Biomedical Research Centre, Breast Cancer Now, Cancer Research UK, the Movember Foundation, and the Bobby Moore Fund for Cancer.
Co-author Lawler disclosed support from Pfizer, EMD Merck, Serono, and Roche unrelated to this work.
Imperiale disclosed no competing interests relevant to his comments.
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