Organ Preservation in Rectal AdenoCa Using Hypofractionated Pelvic RT(Hypo-OPRA)

Inclusion Criteria: * Histologically confirmed invasive adenocarcinoma of the rectum * Pelvic MRI defined disease (at least one of the following): mesorectum involved or breached - includes involvement of adjacent organ(s) (T3-T4) * Patients are considered medically fit for oncologic resection * ECOG performance status 0 or 1 * No evidence of established metastatic disease (CT chest and abdomen) * Absolute neutrophil count \>1.5x109/L; platelets \>100x109/L, * Serum transaminase \<3 x ULN; * Adequate renal function (Cockroft Gault estimation \>50 mL/min) * Bilirubin \<1.5 x ULN * Ability to comply with oral medication * Willingness and ability to give informed consent and comply with treatment and follow up schedule * Age 18 or over Exclusion Criteria: * Previous chemotherapy * Previous radiotherapy to the pelvis (including brachytherapy) * Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months of randomisation) * T1 or T2 N0 disease without extra-mural venous invasion * Unequivocal evidence of metastatic disease (includes resectable metastases) * Major impairment of bowel function without defunctioning stoma/ileostomy (baseline grade 3 diarrhoea or clinically significant faecal incontinence * Known dihydropyrimidine dehydrogenase deficiency * History of another malignancy within the last 5 years except successfully treated basal cell cancer of skin or carcinoma in situ of uterine cervix. * Known Gilberts disease (hyperbilirubinaemia) * Taking warfarin or phenytoin or sorivudine * Gastrointestinal disorder which would interfere with oral therapy and its bioavailability * Pregnant, lactating, or pre-menopausal women not using adequate contraception * Unfit to receive any study treatment or subsequent surgical resection