Recurrence monitoring using ctDNA in patients with metastasis of colorectal cancer: COSMOS- oligo study

Abstract The best treatment strategy for resectable metastatic colorectal cancer is surgical resection of the metastatic site. However, approximately 60% of patients show recurrence after the resection of metastatic lesions, and some patients require aggressive perioperative chemotherapy. We initiated new trials to evaluate the clinical benefits of circulating tumor DNA analysis and refine precision adjuvant therapy for resectable metastatic colorectal cancer, named COSMOS-oligo trials, including two studies. The COSMOS-CRC03 study is a prospective observational study to monitor circulating tumor DNA in patients with metastatic colorectal cancer who can undergo complete surgical resection. The AURORA trial is a randomized Phase II study designed to test whether postoperative mFOLFOXIRI plus bevacizumab is superior to the standard therapy with FOLFOX6 for 6 months in patients with metastatic colorectal cancer if the circulating tumor DNA status is positive at week 4 after curative surgery in the COSMOS-CRC03 study. In these studies, only patients with resectable distant metastases of colorectal cancer will be included. The study will examine the negative predictive value of circulating tumor DNA for recurrence, whether stratification using 28-day postoperative circulating tumor DNA results can select a population with a good prognosis, and whether circulating tumor DNA testing every 12 weeks will detect recurrence earlier than diagnostic imaging. Further, the Phase II trial will determine whether intensive treatment of circulating tumor DNA-positive cases can reduce recurrence. Stage IV colorectal cancer has no standard perioperative treatment. We designed this study to stratify patients using circulating tumor DNA and determine the optimal treatment. COSMOS-CRC03(jRCT2072220055); AURORA trial(jRCT1071220087)