Journal: Nature medicine
This multicenter, randomized phase 2/3 trial evaluated the use of circulating tumor DNA (ctDNA) to guide adjuvant chemotherapy in stage III colon cancer.
Patients were tested for ctDNA 5-6 weeks post-surgery and assigned to either ctDNA-guided or standard treatment.
- ctDNA-negative patients received de-escalated therapy, resulting in significantly reduced oxaliplatin use and fewer hospitalizations.
- This group had a slight, non-inferior decrease in 3-year recurrence-free survival (RFS) compared to standard care (85.3% vs. 88.1%).
- ctDNA-positive patients showed that higher ctDNA levels correlated with worse outcomes.
- However, intensifying chemotherapy did not improve 2-year RFS (51% vs. 61%).
- Persistent ctDNA post-treatment strongly predicted poor prognosis (3-year RFS 14% vs. 79%).
Overall, ctDNA is validated as a strong prognostic biomarker. De-escalation guided by ctDNA reduces toxicity without compromising outcomes, while chemotherapy escalation requires alternative approaches.