Dr Fakih on the Rational Application of Repeat ctDNA Testing in CRC

"The take-home message is that both liquid biopsy and tissue [biopsy] are important... making sense of both sets of data together and analyzing them is what's important, not relying on only one [or] the other."

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 the clinical utility and current limitations of circulating tumor DNA (ctDNA) in colorectal cancer (CRC) based on his presentation at the 11th Annual School of Gastrointestinal Oncology®, an event held by Physicians’ Education Resource.

A central take-home message from his presentation is the necessity of analyzing tissue and liquid biopsy data in tandem rather than relying on one exclusively, Fakih shared. However, he cautioned that repeat liquid biopsies are frequently "overdone" in the community setting without a clear clinical benefit. For instance, in patients with a known driver mutation such as KRAS G12D, repeating ctDNA testing upon progression on chemotherapy is unlikely to uncover new, actionable biomarkers. In such scenarios, repeated testing increases health care costs without providing information that would meaningfully alter the treatment trajectory, he explained.

Conversely, Fakih highlighted specific scenarios where repeat ctDNA testing is clinically rational and data driven. One such case involves patients who have progressed on anti-EGFR therapies, such as cetuximab (Erbitux) or panitumumab (Vectibix). Repeating ctDNA in this population can help oncologists identify the specific mechanisms of resistance. Furthermore, repeat testing is essential for patients being considered for an anti-EGFR rechallenge. If a liquid biopsy performed 6 to 8 months after stopping the initial therapy shows that resistance mutations have cleared, a rechallenge may be appropriate, he noted. Fakih concluded that although ctDNA is a powerful tool, its application must be governed by rational clinical questions to truly benefit the patient.