The impact of lag time to cancer diagnosis and treatment on clinical outcomes prior to the COVID-19 pandemic: a scoping review of systematic reviews and meta-analyses
- McGill University, Canada
Abstract
Background: The COVID-19 pandemic has disrupted cancer care, raising concerns regarding the impact of wait time, or 'lag time', on clinical outcomes. We aimed to contextualize pandemic-related lag times by mapping pre-pandemic evidence from systematic reviews and/or meta-analyses on the association between lag time to cancer diagnosis and treatment with mortality- and morbidity-related outcomes.
Methods: We systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library of Systematic Reviews for reviews published prior to the pandemic (1 January 2010-31 December 2019). We extracted data on methodological characteristics, lag time interval start and endpoints, qualitative findings from systematic reviews, and pooled risk estimates of mortality- (i.e., overall survival) and morbidity- (i.e., local regional control) related outcomes from meta-analyses. We categorized lag times according to milestones across the cancer care continuum and summarized outcomes by cancer site and lag time interval.
Results: We identified 9,032 records through database searches, of which 29 were eligible. We classified 33 unique types of lag time intervals across 10 cancer sites, of which breast, colorectal, head and neck, and ovarian cancers were investigated most. Two systematic reviews investigating lag time to diagnosis reported different findings regarding survival outcomes among pediatric patients with Ewing's sarcomas or central nervous system tumours. Comparable risk estimates of mortality were found for lag time intervals from surgery to adjuvant chemotherapy for breast, colorectal, and ovarian cancers. Risk estimates of pathologic complete response indicated an optimal time window of 7-8 weeks for neoadjuvant chemotherapy completion prior to surgery for rectal cancers. In comparing methods across meta-analyses on the same cancer sites, lag times, and outcomes, we identified critical variations in lag time research design.
Conclusions: Our review highlighted measured associations between lag time and cancer-related outcomes and identified the need for a standardized methodological approach in areas such as lag time definitions and accounting for the waiting-time paradox. Prioritization of lag time research is integral for revised cancer care guidelines under pandemic contingency and assessing the pandemic's long-term effect on patients with cancer.
Funding: The present work was supported by the Canadian Institutes of Health Research (CIHR-COVID-19 Rapid Research Funding opportunity, VR5-172666 grant to Eduardo L. Franco). Parker Tope, Eliya Farah, and Rami Ali each received an MSc. stipend from the Gerald Bronfman Department of Oncology, McGill University.
Data availability
This is a scoping review of peer-reviewed scientific literature. Data used came from scientific manuscripts which can be accessed online. All relevant information is included in the manuscript.
Article and author information
Author details
Funding
Canadian Institutes of Health Research (VR5-172666)
- Eduardo L Franco
McGill University, Gerald Bronfman Department of Oncology (MSc Stipend)
- Parker Tope
- Eliya Farah
- Rami Ali
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Diane M Harper, University of Michigan, United States
Version history
- Preprint posted: June 22, 2022 (view preprint)
- Received: June 23, 2022
- Accepted: January 24, 2023
- Accepted Manuscript published: January 31, 2023 (version 1)
- Version of Record published: February 14, 2023 (version 2)
Copyright
© 2023, Tope et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The impact of lag time to cancer diagnosis and treatment on clinical outcomes prior to the COVID-19 pandemic: a scoping review of systematic reviews and meta-analyses
eLife 12:e81354.
https://doi.org/10.7554/eLife.81354
Further reading
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Background:
Few national-level studies have evaluated the impact of ‘hybrid’ immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Methods:
From May 2020 to December 2022, we conducted serial assessments (each of ~4000–9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results:
Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11–14%) before omicron to 78% (76–80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions:
Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform.
Funding:
Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael’s Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
