Does cell-free DNA influence MRD testing in post-operative colon cancer?

Although cell-free (cf)DNA is significantly increased in the first 14 days after surgery in patients with colon cancer, this did not influence circulating tumour (ct)DNA detection. Furthermore, minimal residual disease (MRD) testing delivered similar results between weeks 2 to 4 after surgery as did testing between weeks 4 to 8 after surgery, implying that standard MRD testing could be initiated as early as 2 weeks post-surgery.

“A sudden increase in cfDNA, which may occur after surgery in patients with colorectal cancer (CRC), could potentially reduce assay sensitivity in the context of measuring ctDNA,” said Dr Stacey Cohen (University of Washington, WA, USA) [1]. “Also, the ideal timing to test for ctDNA after surgery or other events increasing cfDNA, such as systemic therapy, is yet to be determined.” The current study analysed cfDNA kinetics and its impact on MRD detection via ctDNA measurement in patients with colon cancer [2]. The study included 14,425 patients with stage 1–3 colon cancer and at least 1 ctDNA result. In addition, a fully annotated cohort included 450 patients.

ctDNA was significantly increased in the first 2 weeks after surgery, decreased in weeks 2 to 4, and further decreased in weeks 4 to 8 (P<0.0001). In the fully annotated cohort, it was shown that patients on treatment had higher cfDNA levels than patients who were ‘on surveillance’ only. In the first 2 weeks after surgery, variability in ctDNA-positivity was reported. Although cfDNA levels were still high in weeks 2 to 4, ctDNA was consistently detected, with similar results as in weeks 4 to 12, indicating that ctDNA testing may be executed as soon as 15 days after surgery. It was further established that cfDNA concentration did not influence ctDNA-positivity, but that the results beyond 8 weeks after surgery are likely confounded by adjuvant chemotherapy.

In short, post-operative surges in cfDNA concentration did not impact ctDNA detection in a population of patients with colon cancer. Furthermore, according to the results of this study, standard MRD testing could be initiated 2 weeks after surgery.

1. Henriksen T, et al. Mol Oncol. 2020;14(8):1670–1679.
2. Cohen SA, et al. Circulating tumor DNA (ctDNA) for response assessment in patients with anal cancer treated with definitive chemoradiation. Abstract 5, ASCO-GI 2023, San Francisco, CA, USA, 19-21 January.

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Posted on 17 March, 2023