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.

Interventions: 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.
Primary outcome(s): 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.[Patients from both Arms will be followed up every 3 months for the first 2 years and then every 6 months for the next 3 years.]
Study Design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Efficacy