Lay summary
New Zealand has one of the highest rates of rectal cancer in the world, and a quarter of people with rectal cancer have secondary spread of cancer at the time of diagnosis. We propose a single arm phase 2 study with blood and tumour biopsy collection to test the effectiveness of a ""chemo first"" approach to this group of patients. Circulating tumour DNA (ctDNA) will be collected and assessed as: a surrogate for biopsy of the primary and metastases; tumour response to therapy; and to detect developing mutations that might predict resistance to chemotherapy. Multiple biopsies will be collected over time to identify changes in tumour gene expression that will help understand molecular evolution of rectal cancer, and to identify (and later target) the emerging ""lethal clone"".