Interpreting the GALAXY and BESPOKE CRC Data: Transient ctDNA Clearance and the Risk of Recurrence
Experts discuss how ctDNA dynamics after colorectal cancer surgery can guide personalized surveillance and treatment, with recurrent positivity signaling high relapse risk and potential therapy resistance, whereas sustained negativity may support less intensive monitoring, balancing effective oversight with patient quality of life.
The pooled analysis explored outcomes for colorectal cancer patients who were circulating tumor DNA (ctDNA)–ctDNA-positive after surgery, achieved transient ctDNA clearance during adjuvant chemotherapy, but later reverted to positivity. Data showed that approximately 80% of these patients experienced molecular recurrence within 12 to 15 months, indicating rapid recurrence kinetics and suggesting limited durability of ctDNA clearance in many cases. This pattern underscores the importance of ongoing surveillance and may signal early resistance to adjuvant therapy. Persistent or recurrent ctDNA positivity could guide clinicians to consider modifying treatment approaches, such as switching chemotherapy regimens earlier, to achieve better molecular responses.
On the other hand, patients who remain ctDNA-negative beyond 18 months after initially testing positive postoperatively appear to have more favorable outcomes. This prolonged negativity may indicate a meaningful and durable response to therapy. Clinically, it supports a more optimistic outlook for patients and may justify extending the intervals between surveillance scans. Since most gastrointestinal cancer recurrences occur within the first two 2 years after surgery, sustained ctDNA negativity during this period could suggest a lower likelihood of relapse, though ongoing vigilance remains essential due to the risk of late recurrences between years three 3 and five5.
These findings also point to the psychological and financial burden of intensive surveillance. Many patients experience "scanxiety" due to the stress and unpredictability surrounding frequent imaging and insurance coverage. By integrating ctDNA testing into follow-up care, clinicians may be able to personalize surveillance schedules more effectively—, providing reassurance to patients with durable ctDNA negativity while still maintaining careful oversight. This evidence-informed approach allows for more nuanced management of recurrence risk and patient well-being, aligning molecular trends with clinical decision-making to improve long-term outcomes and quality of life.
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