Circulating tumor DNA-guided de-escalation or escalation of adjuvant therapy in high-risk stage II and stage III colon cancer: the phase 2 PEGASUS trial

The phase 2 PEGASUS trial demonstrated the feasibility of a dynamic circulating tumor DNA (ctDNA)-guided strategy for personalizing adjuvant and post-adjuvant therapy in patients with resected microsatellite-stable, high-risk stage II or III colon cancer. Marsoni et al. showed that serial ctDNA monitoring can inform real-time decisions to de-escalate treatment in ctDNA-negative patients and escalate in ctDNA-positive patients, moving beyond a one-size-fits-all chemotherapy approach. The study, published in Nature Cancer, provides a framework for biomarker-driven adaptive therapy that could spare low-risk patients unnecessary toxicity while intensifying treatment for those at higher recurrence risk.