Anatomical vs. Non-Anatomical Resection of Liver Metastases—A Comparison of Two Surgical Techniques in Patients with RAS-Mutated Colorectal Cancer

Colon cancer and rectal cancer (collectively referred to as colorectal cancer) are malignant diseases caused by the uncontrolled proliferation of cells in the intestinal mucosa. An important protein involved in the development of colorectal carcinoma is the RAS protein. It regulates cell growth and can be altered by mutation in such a way that cancer cells grow uncontrollably. If a RAS mutation is detected, drug therapy must be adjusted, as certain targeted therapies are ineffective and alternative treatment options must be selected.

When the cancer spreads to other organs (metastasis), the liver is often affected. If there are only a few or isolated metastases, surgery may be an option; if the metastasis is completely removed surgically (R0), a cure may still be possible. There are two surgical methods for removing liver metastases in which only part of the liver is removed (partial liver resection): In what is known as an anatomical resection, entire liver segments are removed, guided by the liver’s natural blood supply. The second method is non-anatomical resection, in which only the tumor is removed with a small safety margin. The advantage of this method is that, as a rule, more healthy and functional liver tissue is preserved. However, recent data from the U.S. suggest that, in patients with liver metastases originating from colorectal carcinoma with a RAS mutation, anatomical resection is superior to non-anatomical resection. To date, the choice of surgical technique has been made independently of genetic alterations. Both methods are standard surgical procedures and are routinely performed.

The goal of the ARMANI study is to determine whether anatomical resection of liver metastases in RAS-mutated colorectal cancer prolongs disease-free survival compared to non-anatomical resection. To this end, patients are randomly assigned to one of the two study arms, and the metastases are resected either anatomically or non-anatomically. The study is double-blind, meaning that neither the patient nor the study evaluator knows which method was used. The surgeon is not blinded and knows which study arm the patient is in. Following the procedure, patients are monitored for up to 2 years as part of the study. The primary endpoint is intrahepatic disease-free survival (iDFS), defined as the time to recurrence of the disease in the liver. Other factors being monitored include the course of the surgery, as well as postoperative recovery and health. The resection is performed as a single surgical procedure.

Women and men with colorectal carcinoma harboring a RAS mutation (KRAS or NRAS mutation) who have one or more liver metastases are eligible to participate in the study. The liver metastases must be completely resectable. Metastases outside the liver are only eligible if they are resectable or treatable with radiation. Patients receiving palliative care are not eligible to participate in the study.