Clinical Research Directory

Inclusion Criteria: * Biopsy proven adenocarcinoma of the rectum * MRI-defined ≤T3b (with ≤5mm of mesorectal invasion) rectal tumour or endorectal ultrasound-defined ≤uT3b rectal cancer (optional: in centres where high quality endorectal ultrasound (ERUS) is available or patient unable to tolerate MRI) * MDT determines that all of the following treatment options are reasonable and feasible: --TME surgery, (b) CRT (c) SCRT d) TEM. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * For patients choosing organ preservation only: * If female and of childbearing potential, must: * Have a negative pregnancy test within 7 days prior to study entry * Agree to use adequate, medically approved, contraceptive precautions from trial entry until 6 months after the end of study treatment * If non-sterilised male male with a partner of childbearing potential, must: * Agree to use adequate, medically approved, contraceptive precautions from trial entry until 6 months after the end of study treatment * Patient able and willing to provide written informed consent for the study Exclusion Criteria: * Concomitant or previous malignancies within 3 years prior to trial entry, except those that in the opinion of the MDT are unlikely to relapse within 3 years or lead to death within 5 years * Unequivocal evidence of metastatic disease (includes resectable metastases) \-- Patients with equivocal radiological lesions (e.g. retroperitoneal, liver, lung) that are not classified as M1 are eligible if agreed by MDT * MRI node positive (≥N1, defined by protocol guidelines) \-- Patients with equivocal radiological findings that are either classified as NX or N0 are eligible * MRI extramural vascular invasion (mriEMVI) positive (defined by protocol guidelines) * MRI defined mucinous tumour * Mesorectal fascia threatened (≤1 mm on MRI or ERUS) * Maximum tumour diameter \> 40mm (either measured from everted edges on sagittal MRI or on ERUS) * Tumour position anterior, above the peritoneal reflection on MRI or EUS * No residual luminal tumour following endoscopic resection * Contraindications to radiotherapy including previous pelvic radiotherapy * Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction or arrhythmia within 6 months prior to trial entry) * Known complete dihydropyrimidine dehydrogenase (DPYD) deficiency * Known Gilbert's disease (hyperbilirubinaemia) * Taking coumarin-derivative anticoagulants (e.g. warfarin) that cannot be discontinued at least 7 days prior to starting treatment or substituted by low molecular weight heparin * Taking phenytoin or sorivudine or its chemically related anologues, such as brivudine, within 4 weeks of trial entry (see Section 8.3.5 for further details) * Taking metronidazole at study entry * Pregnant or lactating women * History of severe and unexpected reactions to fluoropyrimidine therapy * Age \<16 years (UK), \<18 years (other countries)