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

Prior treatment

• 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)
• 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

Other illness

• 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
• Known Gilbert's disease (hyperbilirubinaemia)
• History of severe and unexpected reactions to fluoropyrimidine therapy

Age

• Age \<16 years (UK), \<18 years (other countries)

Other

• 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
• Known complete dihydropyrimidine dehydrogenase (DPYD) deficiency
• 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

• 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