What is the accuracy of the novel imaging method magnetic resonance tumour regression grade (mrTRG) in assessing tumour response to chemoradiotherapy in patients with rectal cancer?

Study setting 1. University Surgical Unit of the Colombo South Teaching Hospital 2. National Cancer Institute, Maharagama

Method of Randomisation - simple randomisation with 2:1 ratio to intervention and control arms

Intervention
Patients in the intervention arm will be split into one of two groups according to their response to chemoradiotherapy. Patients who show a good response (mrTRG I&II) will be offered deferral of surgery and receive the standard 24-weeks of chemotherapy.

Patients who show a poor response (mrTRG III-V) will receive 12 weeks of chemotherapy (CAPOX [capecitabine and oxaliplatin] or FOLFOX [5-fluorouracil, oxaliplatin, folinic acid], or single agent capecitabine or 5-fluorouracil), undergo repeat restaging, and then continue to surgery or defer surgery, and receive the remaining 12 weeks of chemotherapy.

Control
Patients in the control arm will undergo surgery and then receive a 24-week course of chemotherapy (CAPOX [capecitabine and oxaliplatin] or FOLFOX [5-fluorouracil, oxaliplatin, folinic acid], or single agent capecitabine or 5-fluorouracil) and follow-up assessments as standard i.e. standard clinical practice. The doses will be titrated according to standard protocols.

All doses will be titrated according to standard protocols Both groups will be received other supportive care with no difference.

1. Male and female patients aged 18 years and older
2. Have a biopsy-confirmed adenocarcinoma 0-15cm from the anal verge (on MRI or rigid sigmoidoscopy).
3. Have locally Advanced Rectal Carcinoma diagnosed by MRI (mrCRM unsafe or >mrT3c [>5mm beyond muscularis propria] or mrEMVI positive disease)
4. Be deemed to require chemoradiotherapy.
5. Scheduled to receive 45Gy - 55Gy long course radiotherapy.
6. Have provided written informed consent to participate in the study.

1. Have metastatic disease (including resectable liver metastases).
2. Are contraindicated for MRI e.g. non-MR compatible hip prosthesis, cardiac pacemaker.
3. Are scheduled to receive less than 45Gy or more than 55Gy long course radiotherapy.
4. Are contraindicated for chemoradiotherapy (CRT)
5. Hypersensitivity or contraindication to the drug(s) associated with the planned choice of systemic chemotherapy (CAPOX, FOLFOX or single agent 5-FU or capecitabine) as stated in the SmPC for each of the drugs.
6. Are receiving or planned to receive treatment outside of that stipulated by the protocol, such as an alternative cytotoxic or investigational drug.
7. Are pregnant, breastfeeding or unable / unwilling to comply with pregnancy prevention guidelines.
8. Any other malignant disease within the preceding 5 years with the exception of non- melanomatous skin cancer, carcinoma in situ and early stage disease with <5% recurrence risk