Short RT Versus RCT,Followed by Chemo and Organ Preservation for Interm and High-risk Rectal Cancer Patients

Inclusion Criteria:

* diagnosis of rectal adenocarcinoma localised 0 - 12 cm from the anocutaneous line as measured by rigid rectoscopy (i.e. lower and middle third of the rectum)
* Staging requirements: High-resolution, thin-sliced (i.e. 3mm) magnetic resonance imaging (MRI) of the pelvis is the mandatory local staging procedure.
* MRI-defined inclusion criteria: presence of at least one of the following high-risk conditions:
* any cT3 if the distal extent of the tumor is \< 6 cm from the anocutaneous line, or
* cT3c/d in the middle third of the rectum (≥ 6-12 cm) with MRI evidence of extramural tumor spread into the mesorectal fat of more than 5 mm (\>cT3b), or
* cT3 with clear cN+ based on strict MRI-criteria
* cT4 tumors, or
* Tany middle/low third of rectum with clear MRI criteria for N+
* mrCRM+ (\< 1mm), or
* Extramural venous invasion (EMVI+)
* Trans-rectal endoscopic ultrasound (EUS) is additionally used when MRI is not definitive to exclude early cT1/T2 disease in the lower third of the rectum or early cT3a/b tumors in the middle third of the rectum.
* Spiral-CT of the abdomen and chest to exclude distant metastases.
* Aged at least 18 years. No upper age limit.
* WHO/ECOG Performance Status 0-1
* Adequate haematological, hepatic, renal and metabolic function parameters:
* Leukocytes ≥ 3.000/mm\^3, ANC ≥ 1.500/mm\^3, platelets ≥ 100.000/mm\^3, Hb \> 9 g/dl
* Serum creatinine ≤ 1.5 x upper limit of normal
* Bilirubin ≤ 2.0 mg/dl, SGOT-SGPT, and AP ≤ 3 x upper limit of normal • Informed consent of the patient

Exclusion Criteria:

* Lower border of the tumor localised more than 12 cm from the anocutaneous line as measured by rigid rectoscopy
* Distant metastases (to be excluded by CT scan of the thorax and abdomen)
* Prior antineoplastic therapy for rectal cancer
* Prior radiotherapy of the pelvic region
* Major surgery within the last 4 weeks prior to inclusion
* Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
* Subject (male or female) is not willing to use highly effective methods of Contraception during treatment and for 6 months after the end of treatment.
* On-treatment participation in a clinical study in the period 30 days prior to inclusion
* Previous or current drug abuse
* Other concomitant antineoplastic therapy
* Serious concurrent diseases, including neurologic or psychiatric disorders (incl. dementia and uncontrolled seizures), active, uncontrolled infections, active, disseminated coagulation disorder
* Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) \< 6 months before enrolment
* Prior or concurrent malignancy \< 3 years prior to enrolment in study (Exception: non-melanoma Skin cancer or cervical carcinoma FIGO stage 0-1), if the patient is continuously disease-free
* Known allergic reactions on study medication
* Known dihydropyrimidine dehydrogenase deficiency
* Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule (these conditions should be discussed with the patient before registration in the trial).