The Evolving Role for Repeat Molecular Testing in Metastatic Colorectal Cancer

Next-generation sequencing (NGS) has impacted the treatment landscape for mCRC, leading to improved outcomes through the use of molecularly targeted and immune checkpoint inhibitor therapies. The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) recommend, at a minimum, initial testing to assess RAS, BRAF, HER2, and microsatellite instability (MSI)/mismatch repair (MMR) status, as these results determine therapeutic eligibility. Broader testing to identify the eligibility for tumor-agnostic therapy for a tumor mutation burden (TMB), NTRK gene fusions, and RET fusions is encouraged for all patients with advanced solid tumors. Patients with metastatic disease may develop progressive disease, often as a result of adaptive resistance mechanisms and selective therapeutic pressure on disease heterogeneity. Repeat biomarker testing at progression has the potential to define these resistance mechanisms and to guide the next therapy or clinical trial enrollment. While these practices have become more commonplace, unified guidelines have yet to be established. In this review of the literature, we evaluate the advantages and pitfalls of sequential biomarker testing during disease progression in patients with mCRC.