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

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

  1. Parker Tope

    Division of Cancer Epidemiology, McGill University, Montreal, Canada
    Competing interests
    Parker Tope, received an MSc. Stipend from the Gerald Bronfman Department of Oncology, McGill University..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7903-1413
  2. Eliya Farah

    Division of Cancer Epidemiology, McGill University, Montreal, Canada
    Competing interests
    Eliya Farah, received an MSc. Stipend from the Gerald Bronfman Department of Oncology, McGill University..
  3. Rami Ali

    Division of Cancer Epidemiology, McGill University, Montreal, Canada
    Competing interests
    Rami Ali, received an MSc. Stipend from the Gerald Bronfman Department of Oncology, McGill University..
  4. Mariam El-Zein

    Division of Cancer Epidemiology, McGill University, Montreal, Canada
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5190-0370
  5. Wilson H Miller Jr.

    Department of Oncology, McGill University, Montreal, Canada
    Competing interests
    Wilson H Miller, reports grants to his institution from Merck, Canadian Institutes of Health Research, Cancer Research Society, Terry Fox Research Institute, Samuel Waxman Cancer Research Foundation, and CCSRI; consultancy for Merck, BMS, Roche, GSK, Novartis, Amgen, Mylan, EMD Serono, and Sanofi; honoraria from McGill University, JGH, BMS, Merck, Roche, GSK, Novartis, Amgen, Mylan EMD Serono, and Sanofi; payments to his institution for participation in a clinical trial within the past 2 years from BMS, Novartis, GSK, Roche, AstraZeneca, Methylgene, MedImmune, Bayer, Amgen, Merck, Incyte, Pfizer, Sanofi, Array, MiMic, Ocellaris Pharma, Astellas, Alkermes, Exelixis, VelosBio, and Genetech..
  6. Eduardo L Franco

    Division of Cancer Epidemiology, McGill University, Montreal, Canada
    For correspondence
    eduardo.franco@mcgill.ca
    Competing interests
    Eduardo L Franco, Senior editor, eLifeELF reports support for the present manuscript in the form of a grant to his institution is his name from the Canadian Institutes of Health Research and the Cancer Research Society (CIHR-COVID-558 19 Rapid Research Funding opportunity, VR5-172666 grant to Eduardo L. Franco); consultancy for Merck; a patent related to the discovery DNA methylation markers for early detection of cervical cancer".
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4409-8084

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

  1. Diane M Harper, University of Michigan, United States

Version history

  1. Preprint posted: June 22, 2022 (view preprint)
  2. Received: June 23, 2022
  3. Accepted: January 24, 2023
  4. Accepted Manuscript published: January 31, 2023 (version 1)
  5. 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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  1. Parker Tope
  2. Eliya Farah
  3. Rami Ali
  4. Mariam El-Zein
  5. Wilson H Miller Jr.
  6. Eduardo L Franco
(2023)
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

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https://doi.org/10.7554/eLife.81354

Further reading

    1. Epidemiology and Global Health
    2. Medicine
    3. Microbiology and Infectious Disease
    Edited by Diane M Harper et al.
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    Background:

    The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission.

    Methods:

    To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018.

    Results:

    Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low-level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes.

    Conclusions:

    Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors.

    Funding:

    This research was funded by the National Institutes of Health, grants R01AI121558, R01AI137395, R01AI155730, F30AI143172, and K24AI134990. Funding was also contributed from the Swedish Research Council, Erling-Persson Family Foundation, and the Yang Fund. RV acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 program supported by the European Union. RV also acknowledges funding by Community Jameel.