Dec. 03, 2024
The American Cancer Society estimates that more than 150,000 people will be diagnosed with colorectal cancer this year in the United States, and approximately 50% of those patients will develop metastases.
Surgical resection to remove colorectal liver metastases can increase five-year survival to 40% to 60% in patients who are appropriate candidates. Despite advances in systemic therapy and interventional radiology that can convert patients who are not eligible for surgical resection into candidates for surgery, a majority of patients present with disease that is too advanced for resection.
Studies support liver transplant for colorectal liver metastases
In highly selective cases, liver transplant can offer significantly improved outcomes for patients with colorectal liver metastases and is an important option when other therapies are not feasible.
Liver transplant is an effective therapy for primary hepatic malignancies such as hepatocellular carcinoma and hilar cholangiocarcinoma with outcomes that are superior to surgical resection. Patients with metastatic neuroendocrine tumors treated with liver transplantation also have demonstrated improved long-term survival when compared with systemic therapies alone.
A 2024 TransMet study published in The Lancet is the first randomized controlled multicenter study to show an improvement in survival rates for patients who receive a liver transplant in addition to chemotherapy when compared with patients who only receive chemotherapy.
The study's authors believe the increased survival rate is likely due to three primary factors that include strict patient selection criteria, the implementation of an expert committee to evaluate liver transplant candidates and fast-tracking patients for transplant to reduce tumor progression.
The TransMet study's findings support unresectable colorectal liver metastases as a criterion for transplantation. The 73% five-year overall survival rate is comparable to the survival rate seen in other patients recommended for liver transplantation. The results also could signal a shift in how liver transplant is viewed as a treatment or cure for patients with metastatic dissemination.
Previous research that laid the foundation for innovative treatment
A Norwegian SECA-1 study showed 60% survival rates after five years. In this study published in the Annals of Surgery in 2015, 21 patients underwent neoadjuvant chemotherapy followed by liver transplantation. While the overall survival rates were acceptable, recurrence rates remained high and at the time of maximal follow-up, only 33% of patients had no evidence of disease.
The results of an additional study by the same group that used more stringent inclusion criteria were published in the Annals of Surgery in 2020. Patients included had a minimum 10% radiographic response to chemotherapy and more than one-year interval between diagnosis and transplant. In this study, the five-year survival rate was 83%.
Additional studies have sought to compare these results to current forms of treatment for colorectal liver metastases. Results showed increased survival when compared with chemotherapy as well as positive trends for low tumor load when compared with portal vein embolization and metastasectomy, in addition to a clear advantage for the same treatment with high tumor load. This data has inspired the adoption of active transplant protocols for patients with colorectal liver metastases at a few centers in the United States.
"The findings of these studies continue to support liver transplant as a viable treatment for patients who might not be candidates for other curative therapies," said Denise M. Harnois, D.O., a transplant hepatologist at Mayo Clinic in Florida. "Our transplant team has performed this innovative treatment since 2023, adding to our robust range of therapies designed to treat metastatic colorectal cancer."
Treatment option at Mayo Clinic
Mayo Clinic is a pioneer in transplant surgery for treating colorectal liver metastases and one of only a few centers in the U.S. to offer the highly complex operation.
To be eligible for transplant, patients must have surgically unresectable colorectal liver metastases and their primary colorectal tumors must have been removed. Patients must be no older than 70 years of age at the time of listing, and otherwise be candidates for liver transplant.
Oncologic criteria for consideration for transplant include:
- Less than or equal to T4a stage on primary tumor pathology.
- No extrahepatic disease.
- Carcinoembryonic antigen (CEA) lower than 80 micrograms per liter or > 50% decrease from the highest CEA.
- Completion of six months of chemotherapy after presence of liver metastases.
- Without evidence of tumor progression.
- No BRAF v600E mutant.
- No high microsatellite instability (MSI-H) or Lynch syndrome.
Potential candidates will undergo a standard work-up for transplant as well as have an MRI of the abdomen and pelvis and a PET-CT scan to rule out extrahepatic disease. If approved by the transplant board, patients will be switched from their current chemotherapy to capecitabine only before being put on the transplant list.
For more information
Dueland S, et al. Chemotherapy or liver transplantation for nonresectable liver metastases from colorectal cancer? Annals of Surgery. 2015;261:956.
Dueland S, et al. Survival following liver transplantation for patients with nonresectable liver-only colorectal metastases. Annals of Surgery. 2020;271:212.
Dueland S, et al. Survival outcomes after portal vein embolization and liver resection compared with liver transplant for patients with extensive colorectal cancer liver metastases. JAMA Surgery. 2021;156:550.
Adam R, et al. Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): Results from a multicentre, open-label, prospective, randomised controlled trial. The Lancet. 2024;404:1107.
Refer a patient to Mayo Clinic.