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The Evolving Role for Repeat Molecular Testing in Metastatic Colorectal Cancer
Nicholas D Kendsersky1, Mariah R Erlick1, Emerson Y Chen1
1Knight Cancer Institute, Oregon Health & Science University, Portland, OR 97239, USA.
Abstract:
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.
Insights
Sequential biomarker testing in metastatic colorectal cancer (mCRC) aids in identifying resistance mechanisms and guiding subsequent treatments. Repeat testing post-progression is crucial for optimizing therapy and clinical trial selection.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Next-generation sequencing (NGS) has transformed metastatic colorectal cancer (mCRC) treatment by enabling targeted and immune therapies.
- Current guidelines (NCCN, ASCO) recommend initial biomarker testing (RAS, BRAF, HER2, MSI/MMR) for therapeutic eligibility.
- Broader molecular profiling for tumor-agnostic therapies (TMB, NTRK, RET fusions) is encouraged in advanced solid tumors.
Purpose of the Study:
- To review the advantages and disadvantages of sequential biomarker testing in mCRC patients during disease progression.
- To highlight the role of repeat biomarker analysis in understanding adaptive resistance mechanisms.
- To inform the development of unified guidelines for sequential testing in mCRC.
Main Methods:
- Comprehensive literature review on sequential biomarker testing in mCRC.
- Analysis of studies evaluating biomarker changes at disease progression.
- Evaluation of current NCCN and ASCO recommendations.
Main Results:
- NGS-driven therapies have improved outcomes in mCRC.
- Repeat biomarker testing can reveal resistance mechanisms and guide subsequent treatment decisions.
- Lack of unified guidelines for sequential biomarker testing presents a challenge.
Conclusions:
- Sequential biomarker testing is essential for managing adaptive resistance in mCRC.
- Repeat molecular profiling can optimize subsequent therapy selection and clinical trial enrollment.
- Standardized guidelines are needed to facilitate consistent implementation of sequential biomarker testing.
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