ctDNA Positivity Appears to Predict Risk of Recurrence, Benefit from Adjuvant Chemotherapy in Resectable CRC

An expert from Natera discusses ctDNA’s predictive and prognostic value in resectable colorectal cancer based on data from the GALAXY cohort of the CIRCULATE-JAPAN platform study.

Post-surgical circulating tumor DNA (ctDNA) level in patients with colorectal cancer (CRC) appeared to effectively predict disease recurrence as well as potential benefit from adjuvant chemotherapy, according to Minetta Liu, MD, chief medical officer of oncology at Natera.

CancerNetwork® spoke with Liu in an interview regarding efficacy findings from the observational GALAXY arm of the CIRCULATE-Japan platform study.

In the GALAXY cohort, post-surgical ctDNA detection 4 weeks following surgery was associated with a higher risk of recurrence (HR, 10.0; P <.0001) and helped to identify patients with stage II or III disease who derived benefit from adjuvant chemotherapy (HR, 6.59; P <.0001).

She also went to describe limitations for the research that should be addressed by ongoing randomized clinical research.


CIRCULATE-JAPAN, just to put this in context, is an adaptive platform with 3 clinical trials, and GALAXY represents the observational arm of that platform study. With this long median follow-up of 16.74 months, we demonstrated that that post-surgical time point at 4 weeks, that ctDNA positivity by [the] Signatera [assay] can be used to represent the higher risk of recurrence, but more importantly, predict benefit from adjuvant chemotherapy.

The major limitation is the simple fact that it's an observational study. This was non-interventional, although physicians were prescribing therapy based on their assessments of what patients’ risk of recurrence. But this [should] be supported by ongoing randomized clinical trials demonstrating utility.


Kotani D, Oki E, Nakamura Y, et al. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with clinical stage II-IV resectable colorectal cancer. Nature Medicine. Published online January 16, 2023. doi:10.1038/s41591-022-02115-4