MONITORING circulating tumour DNA (ctDNA) status in patients who have undergone surgery for colorectal cancer (CRC) may play an important role in the decision-making process surrounding adjuvant chemotherapy. CtDNA may be used to detect molecular residual disease (MRD) in patients, and to monitor the effectiveness of treatment in patients who achieve sustained ctDNA clearance on adjuvant chemotherapy. This research was presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium 2024, in San Francisco, California, USA, between the 18th–20th January 2024.
The significance of this work lies with the high risk of experiencing cancer recurrence in patients who have detectable MRD, and do not receive treatment. The current research compared clinicopathologic factors, and found ctDNA status the most significant risk factor for predicting disease-free survival (DFS). In patients with detectable MRD after surgery (ctDNA+), sustained clearance correlated with 90% 24-month DFS. Furthermore, 98% of patients who initially experienced transient clearance followed by radiological recurrence experienced molecular recurrence by 18 months post-surgery.
A total of 2,860 patients provided ctDNA results in this investigation, during the 2–10 week window for detecting MRD following surgery. Of these, 369 (2.9%) were ctDNA+, and 2,491 (87.1%) were ctDNA-. An analysis of ctDNA dynamics from post-operative MRD detection to a 6-month timepoint revealed that patients who remained ctDNA+ were more than five times more likely to experience a cancer recurrence compared to those who had ctDNA clearance.
Among the 445 ctDNA+ patients in the full study population, 240 received adjuvant chemotherapy, 66.3% of whom had ctDNA clearance. For patients whose ctDNA was positive after surgery, and whose ctDNA turned negative upon chemotherapy treatment, 58% had sustained clearance, compared to 42% of patients who eventually returned to ctDNA+ status. Patients with sustained ctDNA clearance had significantly better DFS. Among ctDNA+ patients treated with adjuvant chemotherapy, ≥50% decrease in ctDNA levels at 6 months was associated with better DFS, compared to patients with a <50% decrease or increase in ctDNA levels (24-month DFS rate: 51% versus 29%).
The next steps will involve the researchers validating the use of ctDNA in guiding patient management, by studying how the addition of trifluridine/tipiracil compared to placebo affects patients with CRC who are ctDNA+ after surgery. In addition, they are also considering the possibility of omitting adjuvant chemotherapy in patients with CRC who are ctDNA- during the MRD detection window after surgery.