Operationalizing Comprehensive Biomarker Testing in Metastatic Colorectal Cancer

This segment centers on the practical implementation of biomarker testing in mCRC and the remaining gaps between evidence and real-world practice. The panel begins by affirming that single-gene testing alone is largely obsolete, with most institutions relying on comprehensive NGS using both tissue and liquid biopsy. However, targeted single-gene assays, such as rapid KRAS testing, still play a role in select scenarios, particularly when expedited results are needed for clinical trial eligibility.

Faculty discuss turnaround time expectations, noting that while 24-hour NGS would be ideal, it is not strictly necessary for routine care. Liquid biopsy with a 7–10-day turnaround is generally sufficient and can meaningfully alter treatment plans, even leading to same-day changes in systemic therapy when actionable results return. The panel emphasizes that timely testing requires deliberate workflow planning and clinician attentiveness, but the clinical benefit justifies the effort.

The discussion revisits the unexpectedly strong impact of early targeted therapy in BRAF V600E–mutated disease, reinforcing enthusiasm for moving additional targeted agents, such as KRAS inhibitors, into the frontline setting. Although early KRAS G12D inhibitors have shown more modest activity in CRC, faculty express optimism that combination strategies and earlier use may replicate the success seen in trials like BREAKWATER.

Despite progress, the panel highlights sobering real-world data showing that only 60–70% of patients with CRC undergo BRAF testing, underscoring persistent systemic barriers. Faculty stress the need for better institutional workflows, clinician education, and patient empowerment to close this gap.

Finally, the group cautions against overreliance on ctDNA alone, particularly in cases with low tumor fraction, and advocates for complementary tissue-based testing whenever feasible. The segment concludes with consensus that comprehensive, early, and multimodal biomarker testing is foundational to modern CRC care and essential to delivering precision oncology equitably.