Use of circulating tumour DNA (ctDNA) results to inform the decision for adjuvant chemotherapy in patients with locally advanced rectal cancer who have been treated with pre-operative chemo-radiation and surgery.

INTERVENTION: The study involves blood collection for ctDNA analysis in patients with locally advanced rectal cancer who have undergone pre‐operative long course chemo‐radiation and surgery. Two ctDNA samples are collected initially in the outpatient setting; at weeks 4 and 7 post surgery. Patients are then randomised to either the standard of care (SOC) arm or the ctDNA‐informed arm. ctDNA‐informed arm: Patients who have either a positive ctDNA result OR a negative ctDNA result and have a tumour that is at high‐risk of recurring (based on the standard pathology risk assessment of their tumour) will go on to have chemotherapy which will consist of 4 months of either 5FU or Capecitabine with or without Oxaliplatin. Up to a total of five ctDNA blood samples will be collected from each patient during (monthly) and at completion of chemotherapy. SOC arm; A decision regarding adjuvant chemotherapy will be based on the standard pathology risk assessment of their tumour. Chemotherapy will consist of 4 months of treatment with either 5FU or Capecitabine with or without Oxaliplatin. No further ctDNA samples will be collected in this group of patients. All patients will be follow up in the outpatient setting every 3 months for the first 2 years then every 6 months for 3 years out to 5 years in total. In the follow up period, a blood test for CEA (carcinoembryonic antigen; a tumour marker) will be collected at each visit. A CT scan will be done every 6 months for the first 2 years then at 3 years and thereafter only if clinically indicated. CONDITION: Locally advanced rectal cancer treated with pre‐operative long course chemo‐radiation and surgery PRIMARY OUTCOME: To evaluate whether an adjuvant therapy strategy based on ctDNA results in addition to standard pathologic risk assessment may affect the number of patients treated with chemotherapy. SECONDARY OUTCOME: To correlate the change of serial ctDNA measurements during treatment with disease recurrence and overall survival. To evaluate whether an adjuvant therapy strategy based on ctDNA results affects overall recurrence‐free survival in patients with locally advanced rectal cancer. Recurrence is assessment by blood tests for CEA and CT scans. To evaluate whether an adjuvant therapy strategy based on ctDNA results may affect overall survival in patients with locally advanced rectal cancer INCLUSION CRITERIA: 1. Aged 18 years of age and over 2. Subjects with locally advanced rectal cancer treated with curative intent 3. Subjects treated with pre‐operative long course chemo‐radiation and surgery 4. CT scan of chest/abdomen/pelvis prior to commencing pre‐operative chemo‐radiation demonstrating no metastatic disease 5. A tumour sample (from the pre‐treatment biopsy or surgery specimen is available for molecular testing within 35 days after surgery 6. Fit for adjuvant (post surgery) chemotherapy