Can we Save the Rectum by Watchful Waiting or TransAnal Surgery Following (Chemo)Radiotherapy Versus Total Mesorectal Excision for Early REctal Cancer?

Bowel cancer is the second most common tumour with 41 000 new cases diagnosed annually in the UK, 447 000 across Europe and 1.36 million worldwide; of which one third are located in the rectum. Standard primary radical Total Mesorectal Excision (TME) surgery is an oncologically effective treatment for early stage rectal cancer. However, resection of a low rectal tumour requires a permanent stoma in approximately 10% of cases while many more patients have a temporary stoma, some of which are not reversed. Radical surgery, which evolved to treat locally advanced, symptomatic tumours, may not be the optimal method of treatment for early screen-detected tumours and an organ preserving strategy may generate significantly less morbidity without substantially compromising oncological outcomes. STAR-TREC is a rolling phase II/III study. Phase II aimed to assess the feasibility of a large, multi-centre randomised trial comparing radical surgery versus two contrasting organ saving treatments followed by selective transanal microsurgery. Phase III will evaluate two contrasting organ preservation strategies in terms of organ preservation rates, toxicity (clinician and patient-reported) and Health-Related Quality of Life (HRQoL).

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 \