Circulating tumor DNA using a plasma-only assay predicts survival in patients with oligometastatic colorectal cancer after definitive therapy.

Background: Patients with colorectal cancer (CRC) and oligometastases are usually treated with surgery and radiation. The addition of adjuvant chemotherapy is controversial. The detection of circulating tumor DNA (ctDNA) may provide further insight in prognosis as well as help in decision of adjuvant therapies. We aim to show that detection of ctDNA after definitive therapy in oligometastatic CRC is associated with worse outcomes.

Methods: A single centre prospective study included patients with oligometastatic CRC treated with surgery or radiation with definitive intent. Plasma samples were collected before procedure and 4 weeks after, prior to adjuvant chemotherapy. Plasma samples were analyzed using a tumor-naive assay focusing on genomic and methylation alterations (Guardant Reveal). Disease-free survival (DFS) and overall survival (OS) were estimated using Kaplan Meier method.

Results: A total of 25 patients were included: 19 were evaluated at baseline and post-treatment. ctDNA detection at baseline was not associated with any clinicopathological characteristics, neither OS nor DFS. In contrast, patients with ctDNA detection post-treatment had worse OS [hazard ratio (HR): 11.28; 95% confidence interval (CI): 1.31-97.05] and a trend to shorter DFS (HR: 2.97; 95% CI: 0.97-9.06). Patients who were persistently negative or cleared ctDNA had similar outcomes.

Conclusions: ctDNA detection after surgery/radiation in oligometastatic CRC predicts worse OS and DFS. ctDNA could help to guide the decision regarding need of adjuvant chemotherapy in this population.