Circulating tumor DNA guided therapeutic strategies for colorectal cancer patients with multiple small pulmonary-limited nodules: Updated results from the open-label, prospective, phase II cohort study

BackgroundThe treatment of small pulmonary-limited nodules (SPN) in metastatic colorectal cancer (CRC) patients remains controversy since it is uncertain whether it is distant metastasis. This interventional study is the first to explore the clinical value of tumor-informed ctDNA test in identifying low-risk patients for de-escalation therapy and high-risk patients with no evidence of disease (NED) for escalation therapy in advanced CRC patients with SPNs.MethodsAccording to the longest diameter of the SPNs, patients were divided into two cohorts: Cohort 1 (0-1cm) and Cohort 2 (1-2cm). Tumor-informed ctDNA test (OriMIRACLE STM) was planned to perform every three months until progression or 2 years. In general, patients with negative MRD received active surveillance, while patients with positive MRD received intensive examination and local treatments.ResultsA total of 44 metastatic CRC patients with SPNs were successfully enrolled. The positive rate of MRD at baseline was higher in Cohort 2 (66.67%, 16/24) compared to Cohort 1 (45.00%, 9/20). The time of MRD changed from negative to positive was earlier than the time of image confirmation of disease progression (median advancement: 64.5 days, average advancement: 86.60 ± 76.99 days). The PFS was significantly shorter in patients with positive MRD at any time compared with patients with persistently negative MRD (median PFS :185 days vs. not reached, HR: 7.02; 95% CI: 1.639∼30.06; P = 0.002). The patients with MRD changed from negative to positive showed a significantly shorter PFS than those patients with persistently negative MRD (median PFS :175 days vs. not reached, HR: 8.655; 95% CI: 1.75∼42.81; P= 0.002).ConclusionsHigher baseline positive rate of MRD was observed in patients with 1-2 cm SPNs. For patients with initially negative MRD, positive MRD at any time during follow-up could predict extrapulmonary metastasis. Positive MRD could predict disease progression ahead of clinical routine imaging examination. MRD status are closely related to prognosis, which may indicate whether the intensity of imaging examination needs to be adjusted.Clinical trial identificationThis is an ongoing, open-label, prospective phase II cohort study (NCT05495672).Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.