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Meta-Analysis
. 2019 Feb:40:363-374.
doi: 10.1016/j.ebiom.2019.01.050. Epub 2019 Feb 4.

Biomarker concordance between primary colorectal cancer and its metastases

D S Bhullar  1 , J Barriuso  1 , S Mullamitha  1 , M P Saunders  1 , S T O'Dwyer  1 , O Aziz  2
Affiliations
Meta-Analysis

Biomarker concordance between primary colorectal cancer and its metastases

D S Bhullar et al. EBioMedicine. 2019 Feb.

Abstract

Background: The use of biomarkers to target anti-EGFR treatments for metastatic colorectal cancer (CRC) is well-established, requiring molecular analysis of primary or metastatic biopsies. We aim to review concordance between primary CRC and its metastatic sites.

Methods: A systematic review and meta-analysis of all published studies (1991-2018) reporting on biomarker concordance between primary CRC and its metastatic site(s) was undertaken according to PRISMA guidelines using several medical databases. Studies without matched samples or using peripheral blood for biomarker analysis were excluded.

Findings: 61 studies including 3565 patient samples were included. Median biomarker concordance for KRAS (n = 50) was 93.7% [67-100], NRAS (n = 11) was 100% [90-100], BRAF (n = 22) was 99.4% [80-100], and PIK3CA (n = 17) was 93% [42-100]. Meta-analytic pooled discordance was 8% for KRAS (95% CI = 5-10%), 8% for BRAF (95% CI = 5-10%), 7% for PIK3CA (95% CI = 2-13%), and 28% overall (95% CI = 14-44%). The liver was the most commonly biopsied metastatic site (n = 2276), followed by lung (n = 438), lymph nodes (n = 1123), and peritoneum (n = 132). Median absolute concordance in multiple biomarkers was 81% (5-95%).

Interpretation: Metastatic CRC demonstrates high concordance across multiple biomarkers, suggesting that molecular testing of either the primary or liver and lung metastasis is adequate. More research on colorectal peritoneal metastases is required.

Keywords: BRAF; Biomarker; Colorectal cancer; Concordance; PIK3CA; RAS.

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Figures

Fig. 1
Fig. 1
PRISMA flow diagram of the literature search.
Fig. 2
Fig. 2
Forest plot for proportion of discordance of KRAS. The estimate proportion and 95% CI interval at the level of the total number of cases reflects the calculation under a fixed effect model. The estimate proportion and 95% CI interval at the level of the Pooled Discordance Proportion are the random effects pooled estimates to take into account heterogeneity.
Fig. 3
Fig. 3
Forest plot for proportion of discordance of BRAF. The estimate proportion and 95% CI interval at the level of the total number of cases reflects the calculation under a fixed effect model. The estimate proportion and 95% CI interval at the level of the Pooled Discordance Proportion are the random effects pooled estimates to take into account heterogeneity.
Fig. 4
Fig. 4
Forest plot for proportion of discordance of PIK3CA. The estimate proportion and 95% CI interval at the level of the total number of cases reflects the calculation under a fixed effect model. The estimate proportion and 95% CI interval at the level of the Pooled Discordance Proportion are the random effects pooled estimates to take into account heterogeneity.
Fig. 5
Fig. 5
Forest plot for proportion of discordance of studies considering the overall molecular profiles. The estimate proportion and 95% CI interval at the level of the total number of cases reflects the calculation under a fixed effect model. The estimate proportion and 95% CI interval at the level of the Pooled Discordance Proportion are the random effects pooled estimates to take into account heterogeneity.
Supplementary Fig. 1
Supplementary Fig. 1
Funnel plots to study the publication bias of all the subsets analysed. “ALL” labels the studies considering the overall molecular profiles. P-values for asymmetry obtained by the method developed by Egger and colleagues.
Supplementary Fig. 1
Supplementary Fig. 1
Funnel plots to study the publication bias of all the subsets analysed. “ALL” labels the studies considering the overall molecular profiles. P-values for asymmetry obtained by the method developed by Egger and colleagues.
See this image and copyright information in PMC

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