This is an experimental study without drug or device, randomized, open-label, non-profit, sponsored by the IRCCS Sacro Cuore Don Calabria Hospital in Negrar, which will take place at the Department of Advanced Oncological Radiotherapy and 18 other Italian centers.

The reason for this research study is to evaluate whether stereotactic radiotherapy treatment (SABR), in addition to the systemic chemotherapy treatment foreseen by clinical practice for low-intermediate risk oligometastatic colorectal cancer, is able to:

• delay possible local recurrence and/or distant polymetastatic progression
• improve disease-free survival
• reduce side effects in the short and long term

thus inducing an improvement in the quality of life of patients suffering from this type of pathology.

Therefore, as part of this randomized study, before starting first or second line systemic therapy for his tumor, the patient will be randomized to one of the following treatment arms:

• Experimental arm: ablative stereotactic radiotherapy on all sites of oligometastatic disease (from 1 to 3 sites, performed at most within the second cycle of systemic therapy)
• Control arm: no ablative stereotactic radiotherapy to sites of oligometastatic disease

The procedure that is intended to be tested in the experimental arm is a stereotactic radiotherapy treatment on oligometastases (up to a maximum of 3 sites), with ablative dosage (effective biological dose >100 Gy), performed before the start of systemic therapy of I or II line (at most within the second cycle of the same).

It is hoped that the addition of this type of radiotherapy will increase the potential clinical benefit of the treatment in the context of colorectal cancer.

Inclusion Criteria:

• Age ≥18 years
• Histologically confirmed CRC
• Low and intermediate risk oligometastatic colorectal cancer with 1 to 3 metastases, candidate to I or II line systemic treatment (Low risk: 1 to 3 metastases and cumulative tumor volume smaller than 10 cm3; Intermediate risk: 1 to 3 metastases and cumulative tumor volume bigger than 10 cm3).
• Controlled primary tumor regardless of primary surgery or primary systemic treatment
• ECOG/WHO 0-2
• Life expectancy > 6 months
• Lesions ≤ 5 cm
• Adequate organ function for the planned treatment according to local guidelines
• For patients with liver metastases: no cirrhosis or hepatitis, and evidence of adequate hepatic function (Total bilirubin level < 1.5 x institutional ULN; ALT and AST levels < 3.0 x institutional ULN, GGT and alkaline phosphatase levels < 3.0 x institutional ULN; INR and APTT levels < 1.5 x institutional ULN, Albumin > 2.5 mg/dL)
• For patients with liver metastases: unresectable liver metastases (assessed by a surgeon, preferably hepatobiliary) or refusal of liver surgery before study screening.
• If childbearing potential, willing to use an effective form of contraception throughout the duration of the study
• Signed informed consent and willingness to follow the trial procedures

Exclusion Criteria:

• Age < 18 years
• Brain metastases
• Having more than 3 metastases
• Malignant pleural effusion or ascites
• Unable to undergo imaging by either CT scan or MRI
• Evidence of any other medical conditions (such as psychiatric illness, infectious diseases, neurological conditions, physical examination or laboratory findings) that may interfere with the planned treatment or affect patient compliance.
• Pregnancy or breast-feeding