Preoperative Short-Course Radiation Therapy With PROtons Compared to Photons In High-Risk RECTal Cancer (PRORECT)

Inclusion Criteria: Inclusion Criteria - Primary tumour characteristics * Biopsy-proven, newly diagnosed primary rectal adenocarcinoma, i.e. with the lowest part of the tumour less than 16 cm from the anal verge detected using a rigid rectoscope. * Locally advanced tumour fulfilling at least one of the following criteria on pelvic MRI indicating high risk of failing locally and/or systemically: * Clinical stage (c) T4b, i.e. infiltration of an adjacent organ or structure like the prostate, urinary bladder, uterus, sacrum, pelvic floor or side-wall (according to TNM version 8). * cT4a, i.e. peritoneal involvement. * Extramural vascular invasion (EMVI+). * N2-status regarded as metastatic according to ESGAR consensus criteria * Positive MRF, i.e. tumor or lymph node one mm or less from the mesorectal fascia. * Metastatic lateral nodes (lat LN+) according to ESGAR consensus criteria Inclusion Criteria - General * Staging done within 6 weeks before start of radiotherapy. No contraindications to chemotherapy with CAPOX including adequate blood counts, (within 5 weeks prior to randomisation): * white blood count ≥4.0 x 10\*9/L * platelet count ≥100 x 10\*9/L * clinically acceptable haemoglobin levels * creatinine levels indicating renal clearance of ≥50 ml/min * bilirubin ˂35 µmol/l. * ECOG performance score ≤1 * Patient is considered to be mentally and physically fit for chemotherapy with CAPOX as judged by the oncologist. * Age ≥18 years * Written informed consent. * Adequate potential for follow-up. Exclusion Criteria: * Extensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerve roots indicating that surgery will never be possible even if substantial tumour down-sizing is seen. * Presence of metastatic disease or recurrent rectal tumour. Familial Adenomatosis Polyposis coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn's disease or active ulcerative Colitis. * 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. * Known DPD deficiency. * Any contraindications to MRI (e.g. patients with pacemakers). * Medical or psychiatric conditions that compromise the patient's ability to give informed consent. * Concurrent uncontrolled medical conditions. * Any investigational treatment for rectal cancer within the past month. * Pregnancy or breast feeding. * Patients with known malabsorption syndromes or a lack of physical integrity of the upper gastrointestinal tract. * Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial fibrillation, even if controlled with medication) or myocardial infarction within the past 12 months. * Patients with symptoms of peripheral neuropathy. * Patients with pacemaker or ICD * Patients with bilateral hip protheses