Tumor Biomarker Testing for Metastatic Colorectal Cancer: a Canadian Consensus Practice Guideline

Abstract

The systemic therapy management of metastatic colorectal cancer (mCRC) has evolved from primarily cytotoxic chemotherapies to now include targeted agents given alone or in combination with chemotherapy, and immune checkpoint inhibitors. A better understanding of the pathogenesis and molecular drivers of colorectal cancer not only aided the development of novel targeted therapies but led to the discovery of tumor mutations which act as predictive biomarkers for therapeutic response. Mutational status of the KRAS gene became the first genomic biomarker to be established as part of standard of care molecular testing, where KRAS mutations within exons 2, 3, and 4 predict a lack of response to anti- epidermal growth factor receptor therapies. Since then, several other biomarkers have become relevant to inform mCRC treatment; however, there are no published Canadian guidelines which reflect the current standards for biomarker testing. This guideline was developed by a pan-Canadian advisory group to provide contemporary, evidence-based recommendations on the minimum acceptable standards for biomarker testing in mCRC, and to describe additional biomarkers for consideration.

Real-World Study to Assess Patterns of Treatment Practices and Clinical Outcomes in Metastatic Colorectal Cancer Patients with RAS Wild-Type Left-Sided Tumours in Canada

“…Among these 977 patients, 725 (74%) underwent RAS testing prior to or within 30 days of initiating 1L systemic therapy. According to the Canadian Consensus Practice Guidelines on tumour biomarker testing for mCRC, the minimum biomarker testing required across all Canadian jurisdictions for mCRC patients requires testing for KRAS/NRAS, BRAF, and MMR/MSI prior to the initiation of 1L therapy [ 33 ]. The median time from diagnosis to receipt of RAS testing results was 38 days (IQR: 24–61).…”

“…The median time from diagnosis to receipt of RAS testing results was 38 days (IQR: 24–61). The Canadian Consensus Practice Guidelines strongly recommend that biomarker testing results should be reported to the medical oncologist by the time of first consultation to inform first-line treatment decisions [ 33 ]. They recommend a maximum of 10 working days from sample receipt by the testing laboratory to generation of a summary report, with the report being sent to the referring oncologist within 24 h [ 33 ].…”

“…The Canadian Consensus Practice Guidelines strongly recommend that biomarker testing results should be reported to the medical oncologist by the time of first consultation to inform first-line treatment decisions [ 33 ]. They recommend a maximum of 10 working days from sample receipt by the testing laboratory to generation of a summary report, with the report being sent to the referring oncologist within 24 h [ 33 ]. Given that these guidelines were published in 2022, we anticipate the proportion of patients tested for additional biomarkers to increase in future cohorts.…”

Extracellular vesicles in gastric cancer: role of exosomal lncRNA and microRNA as diagnostic and therapeutic targets

“…Biomarkers refer to biomolecules that occur in blood, tissues, and bodily fluids and that can be utilized to evaluate the normal and pathological states objectively ( Presti et al, 2022 ; Vandendriessche et al, 2022 ; Xu et al, 2022 ). The clinical significance of biomarkers lies in their application for the early detection and diagnosis of various diseases, as well as for monitoring the therapeutic response ( Yu I. S. et al, 2022 ; Davenport et al, 2022 ; Holper et al, 2022 ). Due to their stability, sensitivity, and specificity, these typical characteristics of biomarkers allow their use in clinical practice.…”

Current concepts of anti-EGFR targeting in metastatic colorectal cancer

“…For optimal induction therapy, four parameters are crucial to know in every routine clinical practice: RAS mutation status, MSI status, BRAF- V600E status and primary tumor localization ( 79 , 80 ).…”