ctDNA in Upper GI Cancers: Promise, Pitfalls, and What’s Next

Interest in circulating tumor DNA (ctDNA) as a biomarker continues to grow across oncology, but its integration into routine care for esophageal and gastric cancers is still developing. In an interview with Targeted Oncology, Ryan H. Moy, MD, PhD, assistant professor of Medicine and medical oncologist at Columbia University Irving Medical Center, discusses how ctDNA is currently being used in practice and where it may fit into future treatment strategies for upper gastrointestinal malignancies.

Liquid biopsy can complement tumor-based genomic profiling, particularly when available tissue samples are limited or insufficient for comprehensive sequencing. By analyzing tumor-derived DNA circulating in the bloodstream, clinicians may identify actionable molecular alterations that could expand treatment options, including targeted therapies.

Another area of increasing focus is the use of ctDNA to detect minimal residual disease (MRD) following curative-intent treatment. Early research suggests that detectable ctDNA after surgery or perioperative therapy is strongly associated with a higher likelihood of disease recurrence. As a result, ctDNA may eventually play an important role in identifying patients at greatest risk of relapse.

However, while ctDNA shows promise as a prognostic marker, its clinical utility for guiding treatment decisions remains uncertain. Detecting MRD raises critical management questions, according to Moy: should therapy be intensified when ctDNA is present, or could treatment safely be reduced when it is not detected? Evidence to support these types of treatment adjustments is still emerging.

Multiple prospective studies are underway to better define how ctDNA results should influence patient management. As these data mature, ctDNA testing may become increasingly integrated into clinical workflows, helping to refine surveillance strategies, personalize treatment plans, and potentially intervene earlier in patients at high risk for recurrence.

For now, ctDNA represents a promising but still evolving component of precision oncology in esophageal and gastric cancer care.