Dr Fakih on the Strategic Timing and Concordance of Biopsies in CRC

“[If] you have a patient coming in the door to see you, and that patient has metastatic disease, and you don’t have the NGS [ordered] yet, you’re at the mercy of the biopsy, [which] may not be sufficient.”

Marwan G. Fakih, MD, a professor in the Department of Medical Oncology & Therapeutics Research; associate director of Clinical Sciences; medical director of the Briskin Center for Clinical Research; division chief of GI Medical Oncology; and co-director of the Gastrointestinal Cancer Program at City of Hope, discussed why liquid biopsies should be performed at diagnosis to avoid uninformative results after chemotherapy begins.

At the 11th Annual School of Gastrointestinal Oncology®, an event held by Physicians’ Education Resource, LCC, Fakih delivered a presentation on concordance of liquid and tissue biopsy in colorectal cancer and detailed several case studies to illustrate the advantages vs limitations of using either method.

When a patient presents with metastatic disease, clinicians are often "at the mercy" of tissue next-generation sequencing (NGS) results that may be delayed or insufficient, Fakih began. He explained that initiating chemotherapy before obtaining these results creates a significant clinical risk. If the tumor responds to the treatment, circulating tumor DNA (ctDNA) shedding decreases, often leading to uninformative liquid biopsy results. Furthermore, attempting a repeat tissue biopsy on a responding tumor often yields necrotic tissue, leaving the clinician without actionable genomic insights until the disease eventually progresses, Fakih added.

To address this, Fakih advocates for performing a liquid biopsy at the time of diagnosis to serve as a vital backup for tissue NGS. Beyond the logistical advantages, he highlighted the complexities of discordance between liquid and tissue samples, which can occur due to tumor heterogeneity. For example, a patient may harbor two different KRAS mutations with varying allele frequencies depending on which metastatic site is more aggressive or dominant at the time of the draw.

This understanding of clonal dominance is vital for treatment selection. Fakih noted that a patient might harbor a KRAS G12C mutation, but if a concurrent KRAS G12V mutation is more dominant in the ctDNA, that patient is unlikely to derive benefit from a G12C inhibitor such as sotorasib (Lumakras). Ultimately, the strategic coordination of both biopsy modalities is essential for ensuring that clinicians can accurately interpret the tumor’s genetic landscape and provide the most effective personalized therapies, he concluded.