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
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eLife assessment
The results of this work show a non-determinant effect of the COVID pandemic on the logistics of patient care from diagnosis to treatment modalities. The significance of this scoping review relates to the methodologic design of future outcome measures in cancer reporting that include time measurements between important clinical decision points or treatments in a standardized fashion. Without this standardization in reporting, comparisons to different length intervals are impossible and may have a significant impact on patient outcomes. The strength of the evidence is compelling, given the exhaustive nature of the literature review. This work should be seen by all oncologic units and research groups so that time benchmarks can be established that correlate to patient outcomes. These measurements require oncology society uptake and reporting to be effective.
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Abstract
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 9032 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 paediatric 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.
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Author Response
Public Review:
In this article, the authors have taken up the substantial task of combing through thousands of published meta-analyses and systematic reviews, with the goal of identifying the subset that specifically seeks to measure the association between elapsed time ("lag-time") in various milestones of cancer diagnosis or treatment (e.g. time elapse from symptom onset to first seen by primary care physician) and cancer outcomes. Within this subset, they have identified and summarized the findings on how these lag times are related to certain cancer outcomes. For example, how much does a delay in the start of adjuvant chemotherapy after surgery for breast cancer increase the mortality rate for these patients? The overarching goal of this work is to characterize the pre-Covid-19 landscape of these relationships and …
Author Response
Public Review:
In this article, the authors have taken up the substantial task of combing through thousands of published meta-analyses and systematic reviews, with the goal of identifying the subset that specifically seeks to measure the association between elapsed time ("lag-time") in various milestones of cancer diagnosis or treatment (e.g. time elapse from symptom onset to first seen by primary care physician) and cancer outcomes. Within this subset, they have identified and summarized the findings on how these lag times are related to certain cancer outcomes. For example, how much does a delay in the start of adjuvant chemotherapy after surgery for breast cancer increase the mortality rate for these patients? The overarching goal of this work is to characterize the pre-Covid-19 landscape of these relationships and thereby provide a basis for studying what impact the pandemic had on worsened outcomes for cancer patients due to treatment delays. The authors have done an excellent job in their review of systematic reviews and meta-analyses, both describing their methodology well and interpreting their findings. The immediate connection to the Covid-19 pandemic is somewhat tenuous and primarily left to the reader to determine.
We thank Dr. Boonstra for this positive feedback regarding our detail-oriented systematic search and review process. The main concern of Dr. Boonstra was the need to elaborate on the translation component of our results onto the pandemic. We clarify the utility of contextualizing our findings with the pandemic and corresponding revisions to our manuscript.
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eLife assessment
The results of this work show a non-determinant effect of the COVID pandemic on the logistics of patient care from diagnosis to treatment modalities. The significance of this scoping review relates to the methodologic design of future outcome measures in cancer reporting that include time measurements between important clinical decision points or treatments in a standardized fashion. Without this standardization in reporting, comparisons to different length intervals are impossible and may have a significant impact on patient outcomes. The strength of the evidence is compelling, given the exhaustive nature of the literature review. This work should be seen by all oncologic units and research groups so that time benchmarks can be established that correlate to patient outcomes. These measurements require oncology society …
eLife assessment
The results of this work show a non-determinant effect of the COVID pandemic on the logistics of patient care from diagnosis to treatment modalities. The significance of this scoping review relates to the methodologic design of future outcome measures in cancer reporting that include time measurements between important clinical decision points or treatments in a standardized fashion. Without this standardization in reporting, comparisons to different length intervals are impossible and may have a significant impact on patient outcomes. The strength of the evidence is compelling, given the exhaustive nature of the literature review. This work should be seen by all oncologic units and research groups so that time benchmarks can be established that correlate to patient outcomes. These measurements require oncology society uptake and reporting to be effective.
-
Public Review:
In this article, the authors have taken up the substantial task of combing through thousands of published meta-analyses and systematic reviews, with the goal of identifying the subset that specifically seeks to measure the association between elapsed time ("lag-time") in various milestones of cancer diagnosis or treatment (e.g. time elapse from symptom onset to first seen by primary care physician) and cancer outcomes. Within this subset, they have identified and summarized the findings on how these lag times are related to certain cancer outcomes. For example, how much does a delay in the start of adjuvant chemotherapy after surgery for breast cancer increase the mortality rate for these patients? The overarching goal of this work is to characterize the pre-Covid-19 landscape of these relationships and thereby provide a …
Public Review:
In this article, the authors have taken up the substantial task of combing through thousands of published meta-analyses and systematic reviews, with the goal of identifying the subset that specifically seeks to measure the association between elapsed time ("lag-time") in various milestones of cancer diagnosis or treatment (e.g. time elapse from symptom onset to first seen by primary care physician) and cancer outcomes. Within this subset, they have identified and summarized the findings on how these lag times are related to certain cancer outcomes. For example, how much does a delay in the start of adjuvant chemotherapy after surgery for breast cancer increase the mortality rate for these patients? The overarching goal of this work is to characterize the pre-Covid-19 landscape of these relationships and thereby provide a basis for studying what impact the pandemic had on worsened outcomes for cancer patients due to treatment delays. The authors have done an excellent job in their review of systematic reviews and meta-analyses, both describing their methodology well and interpreting their findings. The immediate connection to the Covid-19 pandemic is somewhat tenuous and primarily left to the reader to determine.
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