Liver Transplantation in Colorectal Metastases

According to the 2023 estimates of the American Cancer Society, approximately 106,970 new colon cancer and 46,050 new rectal cancer cases are expected in the United States. In our country, around 20,000 new colorectal cancer cases are diagnosed annually. Based on 2020 data, approximately 12,200 of these are colon cancers and about 8,700 are rectal cancers. https://gco.iarc.fr/

Metastases (spread to other organs) develop in about 50% of colorectal cancer cases. Surgical resection of these metastases in suitable patients increases survival by 40–60%. Although modern systemic therapies and interventional methods can make initially inoperable patients eligible for surgery, it should be remembered that most patients are diagnosed at an advanced stage, where surgery is not an option.

Renewed interest in liver transplantation for colorectal liver metastases

Today, liver transplantation yields better outcomes than surgical resection, especially in primary liver cancers such as hepatocellular carcinoma and Klatskin tumors.

Patients who undergo liver transplantation for metastatic neuroendocrine tumors live significantly longer compared to those receiving only systemic therapy. Although early experiences with liver transplantation for colorectal liver metastases were not very promising, improved understanding of colorectal cancer biology has made transplantation a safer and more viable option.

In 2013, the Norwegian SECA-I study reported a 5-year survival rate of 60%. In this study, published in *Annals of Surgery* in 2015, 21 patients underwent liver transplantation after neoadjuvant chemotherapy. Although overall survival was acceptable, recurrence rates remained high, with only 33% of patients achieving disease-free survival at long-term follow-up.

The subsequent SECA-II study, which had stricter selection criteria, was published in *Annals of Surgery* in 2020. Patients were required to show at least a 10% radiological response to chemotherapy and have at least one year between diagnosis and transplantation. In this study, 5-year survival rates increased up to 83%.

Later studies compared these results for colorectal liver metastases with current treatment modalities. When compared to chemotherapy, transplantation showed superior outcomes—particularly in patients with low tumor burden, where metastasectomy following portal vein embolization provided clear advantages. These results supported the implementation of active liver transplant protocols for this patient group in certain U.S. centers.

Patient selection protocol for liver transplantation

With the support of Dr. Jones and colleagues, Mayo Clinic in Florida is among the few centers offering liver transplantation for colorectal liver metastases. Following a similar protocol in our center, we recommend liver transplantation for colorectal cancer patients with liver metastases for whom other treatment modalities are no longer suitable.

Eligibility criteria for liver transplantation

General criteria

The primary tumor must have been removed.
Liver metastases must be unresectable.
Patients must be under 65 years of age.
Body Mass Index (BMI) must be below 30.
ECOG performance status must be 0 or 1.
Patients must not have significant cardiac problems.

Oncologic criteria

Primary tumor pathology stage: T4a and N1c or lower.
No extrahepatic disease.
Carcinoembryonic Antigen (CEA) < 80 µg/L.
Completion of at least 6 months of chemotherapy after liver metastasis diagnosis.
At least a 10% tumor response to chemotherapy.
No BRAF V600E mutation.
No high microsatellite instability (MSI-H) or Lynch syndrome.
All patients must be approved by a multidisciplinary tumor board.

Patients must consent to receive only living-donor liver grafts.

Potential candidates will undergo a standard organ transplant evaluation, including full abdominal MRI and PET-CT to rule out extrahepatic disease. If deemed suitable by the multidisciplinary board—including the transplant team—these patients will proceed to liver transplantation.