Abstract

BackgroundThere is a clear need for systematic appraisal of models/factors predicting colorectal cancer (CRC) metastasis and recurrence because clinical decisions about adjuvant treatment are taken on the basis of such variables.MethodsWe conducted an umbrella review of all systematic reviews of observational studies (with/without meta-analysis) that evaluated risk factors of CRC metastasis and recurrence. We also generated an updated synthesis of risk prediction models for CRC metastasis and recurrence. We cross-assessed individual risk factors and risk prediction models.ResultsThirty-four risk factors for CRC metastasis and 17 for recurrence were investigated. Twelve of 34 and 4/17 risk factors with p < 0.05 were estimated to change the odds of the outcome at least 3-fold. Only one risk factor (vascular invasion for lymph node metastasis [LNM] in pT1 CRC) presented convincing evidence. We identified 24 CRC risk prediction models. Across 12 metastasis models, six out of 27 unique predictors were assessed in the umbrella review and four of them changed the odds of the outcome at least 3-fold. Across 12 recurrence models, five out of 25 unique predictors were assessed in the umbrella review and only one changed the odds of the outcome at least 3-fold.ConclusionsThis study provides an in-depth evaluation and cross-assessment of 51 risk factors and 24 prediction models. Our findings suggest that a minority of influential risk factors are employed in prediction models, which indicates the need for a more rigorous and systematic model construction process following evidence-based methods.

Highlights

  • There is a clear need for systematic appraisal of models/factors predicting colorectal cancer (CRC) metastasis and recurrence because clinical decisions about adjuvant treatment are taken on the basis of such variables

  • Umbrella review of systematic reviews of risk factors Literature search and eligibility criteria A systematic search was performed in PubMed, Cochrane Library (Wiley), Web of Science (Thomson Reuters), and EMBASE (Ovid) from inception to 7 October 2019, to identify systematic reviews of observational studies with or without a meta-analysis that evaluated the associations between risk factors and risk of metastasis and recurrence in CRC (Additional file 1: Table S1)

  • 51 unique meta-analyses were retained for analysis, which reported 34 unique risk factors for CRC metastasis and 17 risk factors for recurrence (Additional file 1: Table S6 and Table S7)

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Summary

Introduction

There is a clear need for systematic appraisal of models/factors predicting colorectal cancer (CRC) metastasis and recurrence because clinical decisions about adjuvant treatment are taken on the basis of such variables. Metastasis occurs when cancer cells from the original tumor are able to proliferate in local, regional, or distant tissues; lymph nodes; or organs via lymphatic, blood, or even transcoelomic spread [2]. CRC recurrence is defined as local, regional, and distant metastatic recurrence after a diseasefree period [3]. Local recurrence refers to CRC relapse that occurs at the site of original surgical resection [4], while regional recurrence occurs at draining lymph nodes and/or lateral pelvic lymph nodes [3]. It is estimated that 5-year survival rates are around 90%, 70%, and 10% for CRC localized, regional, and distant metastatic stages [6]

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