Mortality due to cancer treatment delay: systematic review and meta-analysisBMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m4087 (Published 04 November 2020) Cite this as: BMJ 2020;371:m4087
- Timothy P Hanna, associate professor123,
- Will D King, associate professor3,
- Stephane Thibodeau, medical resident2,
- Matthew Jalink, research program manager12,
- Gregory A Paulin, medical resident2,
- Elizabeth Harvey-Jones, clinical oncology registrar4,
- Dylan E O’Sullivan, doctoral student3,
- Christopher M Booth, professor1235,
- Richard Sullivan, professor6,
- Ajay Aggarwal, associate professor467
- 1Division of Cancer Care and Epidemiology, Cancer Research Institute at Queen’s University, 10 Stuart Street, 2nd Level, Kingston, ON K7L3N6, Canada
- 2Department of Oncology, Queen’s University, Kingston, ON, Canada
- 3Department of Public Health Sciences, Queen’s University, Kingston, ON, Canada
- 4Department of Clinical Oncology, Guy’s & St Thomas’ NHS Trust, London, UK
- 5Department of Medicine, Queen’s University, Kingston, ON, Canada
- 6Institute of Cancer Policy, King’s College London, London, UK
- 7Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
- Correspondence to T Hanna (or @HannaRadOnc on Twitter)
- Accepted 16 October 2020
Objective To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways.
Design Systematic review and meta-analysis.
Data sources Published studies in Medline from 1 January 2000 to 10 April 2020.
Eligibility criteria for selecting studies Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models.
Results The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings.
Conclusions Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.
Dr Patti Groome is acknowledged for providing thoughtful comments on the evaluation of confounding by indication.
Contributors: Concept and design: TPH, WDK, CMB, RS, AA. Acquisition, analysis, or interpretation of data: TPH, WDK, ST, MJ, GAP, EHJ, DEO, CMB, RS, AA. Statistical analysis: TPH, WDK, DEO. Drafting of the manuscript: TPH, AA, WDK. Critical revision of the manuscript for important intellectual content: TPH, WDK, ST, MJ, GAP, EHJ, DEO, CMB, RS, AA. Administrative, technical, or material support: TPH, WDK, AA. Supervision: TPH, WDK, AA. TPH had full access to all of the data in the study, takes responsibility for the integrity of the data and the accuracy of the data analysis, and is guarantor for this work. TPH is the corresponding author and attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; unrestricted research funding for an unrelated project from Roche (TPH); no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: No ethical approval was required as this was a systematic review and meta-analysis of previously conducted studies.
Data sharing: No additional data available.
The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned (and, if relevant, registered) have been explained.
Dissemination to participants and related patient and public communities: We plan to disseminate the results to patient organisations. Dissemination to study participants is not applicable.
Provenance and peer review: Not commissioned; externally peer reviewed.
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