Impact of SARS-CoV-2 Pandemic on Colorectal Cancer Screening Delay: Effect on Stage Shift and Increased Mortality.

BACKGROUND & AIMS: The SARS-CoV-2 pandemic had a sudden, dramatic impact on healthcare. In Italy, since the beginning of the pandemic, colorectal cancer (CRC) screening programs have been forcefully suspended. We aimed to evaluate whether screening procedure delays can affect the outcomes of CRC screening. METHODS: We built a procedural model considering delays in the time to colonoscopy and estimating the effect on mortality due to up-stage migration of patients. The number of expected CRC cases was computed by using the data of the Italian screened population. Estimates of the effects of delay to colonoscopy on CRC stage, and of stage on mortality were assessed by a meta-analytic approach. RESULTS: With a delay of 0-3 months, 74% of CRC is expected to be stage I-II, while with a delay of 4-6 months there would be a 2%-increase for stage I-II and a concomitant decrease for stage III-IV (P = .068). Compared to baseline (0-3 months), moderate (7-12 months) and long (> 12 months) delays would lead to a significant increase in advanced CRC (from 26% to 29% and 33%, respectively; P = .008 and P < .001, respectively). We estimated a significant increase in the total number of deaths (+12.0%) when moving from a 0-3-months to a >12-month delay (P = .005), and a significant change in mortality distribution by stage when comparing the baseline with the >12-months (P < .001). CONCLUSIONS: Screening delays beyond 4-6 months would significantly increase advanced CRC cases, and also mortality if lasting beyond 12 months. Our data highlight the need to reorganize efforts against high-impact diseases such as CRC, considering possible future waves of SARS-CoV-2 or other pandemics.

Association of COVID-19 Lockdown With the Tumor Burden in Patients With Newly Diagnosed Metastatic Colorectal Cancer.

Importance: The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management. Objective: To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. Design, Setting, and Participants: This cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. Exposures: mCRC. Main Outcomes and Measures: Circulating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020) vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. Results: A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI, 8.8-18.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown. Conclusions and Relevance: This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.

An inverse stage-shift model to estimate the excess mortality and health economic impact of delayed access to cancer services due to the COVID-19 pandemic.

AIM: Decreased cancer incidence and reported changes to clinical management indicate that the COVID-19 pandemic has delayed cancer diagnosis and treatment. This study aimed to develop and apply a flexible model to estimate the impact of delayed diagnosis and treatment on survival outcomes and healthcare costs based on a shift in the disease stage at treatment initiation. METHODS: A model was developed and made publicly available to estimate population-level health economic outcomes by extrapolating and weighing stage-specific outcomes by the distribution of stages at treatment initiation. It was applied to estimate the impact of 3- and 6-month delays based on Australian data for stage I breast cancer, colorectal cancer, and lung cancer patients, and for T1 melanoma. Two approaches were explored to estimate stage shifts following a delay: (a) based on the relation between time to treatment initiation and overall survival (breast, colorectal, and lung cancer), and (b) based on the tumor growth rate (melanoma). RESULTS: Using a conservative once-off 3-month delay and considering only shifts from stage I/T1 to stage II/T2, 88 excess deaths and $12 million excess healthcare costs were predicted in Australia over 5 years for all patients diagnosed in 2020. For a 6-month delay, excess mortality and healthcare costs were 349 deaths and $46 million over 5 years. CONCLUSIONS: The health and economic impacts of delays in treatment initiation cause an imminent policy concern. More accurate individual patient data on shifts in stage of disease during and after the COVID-19 pandemic are critical for further analyses.

Prioritisation by FIT to mitigate the impact of delays in the 2-week wait colorectal cancer referral pathway during the COVID-19 pandemic: a UK modelling study.

OBJECTIVE: To evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent from the COVID-19 pandemic. DESIGN: We modelled the reduction in CRC survival and life years lost resultant from per-patient delays of 2-6 months in the 2WW pathway. We stratified by age group, individual-level benefit in CRC survival versus age-specific nosocomial COVID-19-related fatality per referred patient undergoing colonoscopy. We modelled mitigation strategies using thresholds of FIT triage of 2, 10 and 150 µg Hb/g to prioritise 2WW referrals for colonoscopy. To construct the underlying models, we employed 10-year net CRC survival for England 2008-2017, 2WW pathway CRC case and referral volumes and per-day-delay HRs generated from observational studies of diagnosis-to-treatment interval. RESULTS: Delay of 2/4/6 months across all 11 266 patients with CRC diagnosed per typical year via the 2WW pathway were estimated to result in 653/1419/2250 attributable deaths and loss of 9214/20 315/32 799 life years. Risk-benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients aged >60. Prioritisation out of delay for the 18% of symptomatic referrals with FIT >10 µg Hb/g would avoid 89% of these deaths attributable to presentational/diagnostic delay while reducing immediate requirement for colonoscopy by >80%. CONCLUSIONS: Delays in the pathway to CRC diagnosis and treatment have potential to cause significant mortality and loss of life years. FIT triage of symptomatic patients in primary care could streamline access to colonoscopy, reduce delays for true-positive CRC cases and reduce nosocomial COVID-19 mortality in older true-negative 2WW referrals. However, this strategy offers benefit only in short-term rationalisation of limited endoscopy services: the appreciable false-negative rate of FIT in symptomatic patients means most colonoscopies will still be required.

The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study.

BACKGROUND: Since a national lockdown was introduced across the UK in March, 2020, in response to the COVID-19 pandemic, cancer screening has been suspended, routine diagnostic work deferred, and only urgent symptomatic cases prioritised for diagnostic intervention. In this study, we estimated the impact of delays in diagnosis on cancer survival outcomes in four major tumour types. METHODS: In this national population-based modelling study, we used linked English National Health Service (NHS) cancer registration and hospital administrative datasets for patients aged 15-84 years, diagnosed with breast, colorectal, and oesophageal cancer between Jan 1, 2010, and Dec 31, 2010, with follow-up data until Dec 31, 2014, and diagnosed with lung cancer between Jan 1, 2012, and Dec 31, 2012, with follow-up data until Dec 31, 2015. We use a routes-to-diagnosis framework to estimate the impact of diagnostic delays over a 12-month period from the commencement of physical distancing measures, on March 16, 2020, up to 1, 3, and 5 years after diagnosis. To model the subsequent impact of diagnostic delays on survival, we reallocated patients who were on screening and routine referral pathways to urgent and emergency pathways that are associated with more advanced stage of disease at diagnosis. We considered three reallocation scenarios representing the best to worst case scenarios and reflect actual changes in the diagnostic pathway being seen in the NHS, as of March 16, 2020, and estimated the impact on net survival at 1, 3, and 5 years after diagnosis to calculate the additional deaths that can be attributed to cancer, and the total years of life lost (YLLs) compared with pre-pandemic data. FINDINGS: We collected data for 32 583 patients with breast cancer, 24 975 with colorectal cancer, 6744 with oesophageal cancer, and 29 305 with lung cancer. Across the three different scenarios, compared with pre-pandemic figures, we estimate a 7·9-9·6% increase in the number of deaths due to breast cancer up to year 5 after diagnosis, corresponding to between 281 (95% CI 266-295) and 344 (329-358) additional deaths. For colorectal cancer, we estimate 1445 (1392-1591) to 1563 (1534-1592) additional deaths, a 15·3-16·6% increase; for lung cancer, 1235 (1220-1254) to 1372 (1343-1401) additional deaths, a 4·8-5·3% increase; and for oesophageal cancer, 330 (324-335) to 342 (336-348) additional deaths, 5·8-6·0% increase up to 5 years after diagnosis. For these four tumour types, these data correspond with 3291-3621 additional deaths across the scenarios within 5 years. The total additional YLLs across these cancers is estimated to be 59 204-63 229 years. INTERPRETATION: Substantial increases in the number of avoidable cancer deaths in England are to be expected as a result of diagnostic delays due to the COVID-19 pandemic in the UK. Urgent policy interventions are necessary, particularly the need to manage the backlog within routine diagnostic services to mitigate the expected impact of the COVID-19 pandemic on patients with cancer. FUNDING: UK Research and Innovation Economic and Social Research Council.