Studies have found that the ctDNA blood test can reliably detect “molecular residual disease” (MRD) – essentially, small traces of cancer left after surgery. Patients who test positive for MRD have a higher risk of their cancer returning. In colorectal cancer, circulating tumor DNA (ctDNA) has become a minimally invasive and dependable prognostic biomarker for identifying post-surgical MRD and assessing the risk of recurrence. Post-surgical ctDNA positivity is the most useful prognostic factor for determining recurrence risk in patients with colorectal cancer. The results help identify which patients are likely to benefit from adjuvant chemotherapy. Ongoing studies have been evaluating the impact of MRD and the role of ctDNA testing to predict overall survival.
In a recent update from the CIRCULATE-Japan GALAXY observational study, results reinforced previous studies demonstrating that monitoring ctDNA can help detect MRD and assess the risk of recurrence in patients with resectable CRC. With a 23-month median follow-up involving 2,240 patients with stage II–III colon cancer or stage IV CRC, the study highlights the importance of ctDNA positivity, which was linked to poorer disease-free survival (DFS) and overall survival (OS). Specifically, patients who tested positive for ctDNA had a higher risk of recurrence and shorter survival times, emphasizing the value of regular ctDNA monitoring.
For those undergoing adjuvant chemotherapy (ACT), the study revealed that patients who achieved sustained ctDNA clearance experienced significantly better outcomes compared to those with only temporary clearance. For example, after 24 months, 89% of patients with sustained clearance were disease-free, while only 3.3% of those with transient clearance remained disease-free. Additionally, the spontaneous clearance rate—where patients showed no clinical signs of recurrence—was very low at just 1.9%.
These findings underscore the role of ctDNA monitoring in guiding treatment decisions and improving post-surgical care by better assessing the risk of recurrence and mortality.
This study is part of ongoing research to improve care for colorectal cancer patients. Talk to your oncologist about how new developments like this might affect your treatment plan and whether MRD testing with ctDNA is appropriate for you.
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References:
Nakamura, Y., Watanabe, J., Akazawa, N. et al. ctDNA-based molecular residual disease and survival in resectable colorectal cancer. Nat Med (2024).
Reinert, T. et al. Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol. 5, 1124–1131 (2019).
Loupakis, F. et al. Detection of molecular residual disease using personalized circulating tumor DNA assay in patients with colorectal cancer undergoing resection of metastases. JCO Precis. Oncol. 5, PO.21.00101 (2021).
Kotani, D. et al. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nat. Med. 29, 127–134 (2023).
Kasi, P. M. et al. Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II/III colorectal cancer (CRC): interim analysis of BESPOKE CRC study. J. Clin. Oncol. 42, https://doi.org/10.1200/JCO.2024.42.3_suppl.9 (2024).
