Review Articles

Prognostic and predictive clinical, pathological, and molecular biomarkers in metastatic colorectal carcinoma – a review

Ongoing research increasingly reveals that metastatic colorectal carcinoma (mCRC) is a highly heterogeneous entity. Despite extension of the median survival of mCRC patients due to advances in therapeutic options available, further improvement and better rationalisation of resources could be achieved by more accurately predicting individual patient prognoses and responses to specific treatments. It is hence important to further our understanding of prognostic and predictive biomarkers in mCRC to enable accurate estimation of treatment benefit for individual patients and therefore guide patient selection. This information can also be used for improving patient stratification in future studies. The aim of this literature review is to highlight potential prognostic and predictive clinical, pathological and molecular biomarkers in mCRC. Broad categories include patient and tumour markers, protein markers and cell-free DNA, inflammatory markers and genetic markers.

The potential prognostic and predictive values of factors such as performance status, BRAF mutational status and neutrophil:lymphocyte ratio (NLR) >5 are supported by consistently strong evidence, but interpretation of the roles of other factors is difficult due to inconsistent findings between studies; however, many studies examine only small cohorts of patients, thereby limiting statistical power and variability in cut-off points may have contributed to different findings between trials. Although existing evidence may be used to select patient treatments and guide stratification in trials, future research with larger patient cohorts and clarification of appropriate cut-off values may prove helpful in elucidating the value of these biomarkers.

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