Grant: Project Grant

Introduction: Colorectal cancer (CRC) is the second most common cause of cancer death in Canada and one-third of patients diagnosed have cancer that has spread to their lymph nodes (called stage III). Surgery can cure these patients, but half have cancer return. Chemotherapy after surgery can improve the chance of cure but has significant side effects and many cancers return despite chemotherapy. If surgery did not remove all of a cancer, fragments of cancer DNA can enter the blood stream (called ctDNA). Detecting ctDNA after surgery is a new technology which may identify patients most likely to have cancer come back. This information may help determine which patients should get extra chemotherapy after surgery. There are also new ways to look at which genes a cancer turns on/off (gene expression) that can help explain why some cancers are more aggressive. DYNAMIC-III is a randomised trial that aims to show how we can use ctDNA and gene expression to better select chemotherapy after surgery in stage III CRC. Specific Aims: Determine whether ctDNA and/or gene expression can help select which patients with colorectal cancer are more likely to benefit from chemotherapy after surgery. Methods: This trial will recruit 1000 patients in Canada, Australia, and New Zealand with stage III colorectal cancer to either receive standard chemotherapy after surgery, or to use ctDNA to choose chemotherapy intensity after surgery. In patients without detectable ctDNA, suggesting a lower risk of cancer returning, chemotherapy will be reduced and we aim to show it is still effective, but has less side effects. In patients with ctDNA detected, more chemotherapy will be given to increase the chance of cure. Cancers will also be tested to see if gene expression is useful to help select chemotherapy after surgery. Significance: This trial aims to use new technologies to reduce toxicity and improve the chance of cure for patients with surgically removed colorectal cancer.