A multi-centred, partially randomised, patient-preference trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer.

Prior treatment

• Incomplete or inconclusive resection margin with macroscopic residual tumour.
• Previous pelvic radiation.
• Treatment with any other investigational agent, or participation in another clinical trial that might influence study outcomes within 28 days prior to enrolment.
• Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (<6 months prior to randomisation), myocardial infarction (<6 months prior to randomisation), unstable angina, New York Heart Association (NYHA) grade II or higher, congestive heart failure, serious cardiac arrhythmia requiring medication.

Other illness

• Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
• History of severe and unexpected reactions to fluoropyrimidine therapy.
• Hypersensitivity to capecitabine.
• Patients with severe hepatic impairment.
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent.
• Presence of metastatic disease or recurrent rectal tumour.
• Concomitant malignancies, except for adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri. Subjects with prior malignancies must be disease-free for at least 5 years.

Other

• Patients known with dihydropyrimidine dehydrogenase deficiency.
• Any contra-indications to undergo MRI imaging.
• T1 tumour with carcinoma <3 cm, moderate/well differentiated, without sm3/Haggit4, tumour budding, venous or lymphatic invasion.
• T1 tumour with carcinoma of >5 cm and T2 tumour with carcinoma of >3 cm.
• Pregnancy, breast-feeding or fertile women without active birth control.

• The patient has had an endoluminal local excision (by TEM, TAMIS, TSPM, EMR, ESD, endoscopic full thickness resection, endoscopic intramuscular dissection or polypectomy) of an early rectal cancer without carcinoma in the resection plane.
• Male or female, age > 18 years.
• Life expectancy of at least 12 months.
• Medically fit (WHO 0-2) to undergo radical surgery and/or radiation.
• No contraindications to chemotherapy, including adequate blood counts; white blood count >= 4.0 x 10 9/l, platelet count >=100 x 109/l, clinical acceptable haemoglobin levels, bilirubin < 35 umol/l, creatinine levels indicating renal clearance of >=50 ml/min
• The patient is willing and able to comply with the protocol for the duration of the study, and scheduled follow-up visits and examinations.
• Written (signed and dated) informed consent and be capable of co-operating with protocol.
• Patients with unreliable resection planes (EMR/ESD) are eligible for randomisation if no macroscopic residual tumour is found during endoscopy.
• Patients with carcinoma in the resection plane are eligible for randomisation after re-excision that shows no carcinoma in the resection plane.
• Only lesions for which TME surgery is indicated can be included (if a partial mesorectal excision (PME) is indicated the patient should be excluded).
• Pathological confirmation of the rectal adenocarcinoma fulfilling the following criteria: T1 with size 3-5 cm of carcinoma or pT1, maximum size of carcinoma of 3 cm, with at least poor differentiation, Haggit 4 and/or sm3, tumour budding, lymphatic and/or venous invasion.
• Pathological confirmation of the rectal adenocarcinoma fulfilling the following criteria: pT2, maximum size of carcinoma of 3 cm, well/moderate differentiated and without lymphatic or venous invasion.
• Complete colonoscopy, without synchronous colorectal cancer.
• cN0 stage based on pelvic MRI; lymph nodes smaller than 10 mm will be considered as benign, independent of morphologic features. Staging done within 6 weeks before randomisation.
• Adequate distant staging (X-thorax or CT-thorax and CT-abdomen) without signs of distant metastasis (cM0).