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 info…