Anatomical Resection of Liver MetAstases iN patIents With RAS-mutated Colorectal Cancer

Anatomical Resection of Liver MetAstases iN patIents With RAS-mutated Colorectal Cancer

the ARMANI trial will test the hypothesis, if an anatomic resection (AR) improves long-term outcome vs. a non-anatomical resection (NAR) in patients undergoing surgery for RAS-mutated colorectal liver metastasis (CRLM).

Despite increasing application and success of personalized treatment in medical oncology, little progress has been made in personalized surgical cancer therapy. The ARMANI trial presents the first prospective, randomized trial to evaluate effectiveness and safety of molecular-guided resection in patients with colorectal liver metastasis (CRLM). While CRLM might be removed independently of the liver's segmental borders, retrospective data favor anatomic resections in the subgroup of patients with a mutation in the RAS oncogene. Therefore, the ARMANI trial will test the hypothesis, if an anatomic resection (AR) improves long-term outcome vs. a non-anatomical resection (NAR) in patients undergoing surgery for RAS-mutated CRLM. The trial will be carried out among 11 high-volume centers of hepato-biliary surgery in Germany. A total of 220 patients will be enrolled and randomized in a 1:1 ratio to undergo an AR vs. NAR. The primary endpoint is intrahepatic disease-free survival (iDFS). In addition, the study will provide important data on perioperative outcomes and quality of life for both surgical techniques. Given the trend among liver surgeons to aim for parenchymal-sparing operations to preserve liver parenchyma, a positive trial will be practice changing and present the first piece of high-level evidence on benefits of personalized surgical therapy guided by the tumor's mutational profile in patients with CRLM.

Inclusion Criteria:

• Colorectal cancer with RAS mutation (KRAS or NRAS)
• Colorectal liver metastases (single or multiple)
• Planned R0 resection of liver metastases (and primary tumor, if present)
• Anatomical and non-anatomical liver resection technically feasible
• Male and female patients, age ≥ 18 years
• Written informed consent

Exclusion Criteria:

• Extrahepatic metastases
• Planned staged liver resection (e.g. two-stage hepatectomy)
• Diagnosis of another cancer < 5 years prior to randomization Exceptions: curatively treated in situ cervical cancer, curatively resected non-melanoma skin cancer
• Expected lack of compliance
• Addiction or other illnesses which do not allow the person concerned to assess the nature and extent of the clinical trial and its possible consequences