Circulating tumor DNA (ctDNA) analysis is emerging as a precise tool to determine which patients with resected colorectal cancer and liver metastases benefit from adjuvant chemotherapy. According to findings from the phase II GALAXY study presented at the ESMO Gastrointestinal Cancers Congress, patients who test positive for molecular residual disease (MRD) via ctDNA after surgery show significantly improved survival rates when treated with adjuvant chemotherapy compared to those who forgo the treatment.
Predicting Adjuvant Chemotherapy Benefit via ctDNA
The GALAXY study, a component of the broader CIRCULATE-Japan trial, evaluated whether monitoring ctDNA could refine post-surgical treatment plans. By testing patients 2 to 10 weeks after surgery using the Signatera tumor-informed assay, researchers aimed to identify who truly requires systemic therapy. The updated analysis included 298 patients, split between those who underwent upfront surgery (191 patients) and those who received neoadjuvant chemotherapy (107 patients).
In the upfront surgery cohort, 63 of 129 evaluable patients tested positive for MRD. This presence of residual DNA was a strong predictor of poor outcomes, with a hazard ratio of 4.15 for disease-free survival. These data suggest that ctDNA could eventually serve as a biological marker to guide clinical decision-making, moving away from a one-size-fits-all approach to adjuvant care.
Did you know?
According to Per Pfeiffer, MD, PhD, of Odense University Hospital, only about 1 in 10 patients is currently cured by adjuvant therapy, yet almost all patients face treatment-related side effects. Identifying the right candidates could significantly reduce unnecessary toxicity.
Survival Outcomes in the GALAXY Study
The study’s findings highlight a stark difference in long-term prognosis based on post-surgical treatment choices. Among patients in the upfront surgery cohort, those who received adjuvant chemotherapy demonstrated a 4-year overall survival rate of 65%, compared to only 33% for those who did not receive chemotherapy.
Disease-free survival rates followed a similar trend. Patients treated with adjuvant chemotherapy reached a 38% disease-free survival rate at four years, while those who skipped the treatment saw a rate of just 7%. These figures provide a clear link between ctDNA-guided treatment and reduced risks of cancer recurrence and death.
Clinical Limitations and Future Directions
Despite these promising results, experts caution against immediate, widespread adoption of ctDNA testing in routine clinical practice. Dr. Pfeiffer noted that while the data is compelling, it is not yet robust enough to replace current standard-of-care guidelines outside of clinical trial environments.
The oncology community remains focused on the need for further research, specifically randomized clinical trials, to validate these findings. Standardizing the use of ctDNA assays will be a critical step before they become a routine part of post-surgical monitoring for colorectal cancer patients. The CIRCULATE-Japan trial, which receives support from the Japan Agency for Medical Research and Development and the National Cancer Center Research and Development Fund, continues to lead these efforts.
Pro Tip:
When discussing treatment options with an oncologist, ask if your facility participates in clinical trials that utilize liquid biopsies or ctDNA monitoring, as these trials often provide access to emerging diagnostic technologies before they become standard practice.
Frequently Asked Questions
What is molecular residual disease (MRD) tracking?
MRD tracking uses highly sensitive blood tests—often called liquid biopsies—to detect trace amounts of tumor DNA remaining in the bloodstream after a tumor has been surgically removed. This can indicate that cancer cells are still present even if they are not visible on standard imaging scans.
Is ctDNA testing currently standard of care for colorectal cancer?
No. According to Dr. Per Pfeiffer, current evidence is not yet strong enough for ctDNA to be used routinely outside of clinical trials. Further randomized studies are required to confirm that this approach improves patient outcomes in a general clinical setting.
How does the GALAXY study help patients?
The GALAXY study aims to identify which patients are most likely to benefit from adjuvant chemotherapy. By identifying patients at high risk of recurrence through ctDNA, doctors may be able to provide life-saving treatment to those who need it while sparing others from the unnecessary side effects of chemotherapy.
For more updates on advancements in oncology and clinical trial results, subscribe to our newsletter or explore our cancer research archives. If you have questions about your specific treatment plan, always consult with your primary oncology team.
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