The effect of time before diagnosis and treatment on colorectal cancer outcomes: systematic review and dose-response meta-analysis

Abstract

Background: This systematic review and meta-analysis aimed to evaluate existing evidence on the relationship between diagnostic and treatment intervals and outcomes for colorectal cancer.

Methods: Four databases were searched for English language articles assessing the role of time before initial treatment in colorectal cancer on any outcome, including stage and survival. Two reviewers independently screened articles for inclusion and data were synthesised narratively. A dose-response meta-analysis was performed to examine the association between treatment interval and survival.

Results: One hundred and thirty papers were included in the systematic review, eight were included in the meta-analysis. Forty-five different intervals were considered in the time from first symptom to treatment. The most common finding was of no association between the length of intervals on any outcome. The dose-response meta-analysis showed a U-shaped association between the treatment interval and overall survival with the nadir at 45 days.

Conclusion: The review found inconsistent, but mostly a lack of, association between interval length and colorectal cancer outcomes, but study design and quality were heterogeneous. Meta-analysis suggests survival becomes increasingly poorer for those commencing treatment more than 45 days after diagnosis.

Registration: This review was registered, and the protocol is available, in PROSPERO, the international database of systematic reviews, with the registration ID CRD42021255864.

Fig. 1. PRISMA diagram.

Flowchart of included articles in the systematic review and dose-response meta-analysis.

Fig. 2. Intervals assessed more than once.

Names in brackets refer to intervals defined by the Aarhus statement [5].

Fig. 3. Dose-response meta-analysis results.

Results of the dose–response meta-analysis for all studies (a) and subset of studies (b).