Nov. 20, 2021
Nearly 150,000 patients 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 initially unresectable patients into operative candidates, a majority of patients will present with disease that is too advanced for resection.
Renewed interest in liver transplant for colorectal liver metastases
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 have also demonstrated improved long-term survival when compared with systemic therapies alone. Initial attempts at liver transplantation for patients with colorectal liver metastases over two decades ago, however, were disappointing. Since then, much has been learned about the biology of colorectal cancer and the safety of liver transplantation has significantly improved.
In 2013, the Norwegian SECA-I 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 same group conducted an updated SECA-II study with more stringent inclusion criteria. The results of this study 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 five-year survival was 83%.
Further studies have sought to compare these results to current forms of treatment for colorectal liver metastases, showing increased survival when compared with chemotherapy, positive trends for low tumor load when compared with portal vein embolization and metastasectomy and 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 data around transplantation is really exciting for how we might treat patients with colorectal liver metastases in the future," said Jeremy C. Jones, M.D., Hematology Oncology at Mayo Clinic in Jacksonville, Florida. "While further data is needed to promote widespread adoption of this potentially curative therapy, we are excited to be at the forefront of such treatment changes."
A new protocol at Mayo Clinic in Florida
With support from Dr. Jones and his colleagues, Mayo Clinic physicians Kristopher (Kris) P. Croome, M.D., Denise M. Harnois, D.O., and Beau Toskich, M.D., Mayo Clinic's campus in Jacksonville, Florida, is one of only a few centers in the U.S. offering transplant as a treatment option for colorectal liver metastases. "In highly selected patients, liver transplant can offer significantly improved outcomes for patients with colorectal liver metastases and is an important option for when other therapies are not feasible," said Dr. Croome, who is a transplant and hepatobiliary surgeon.
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 65 years of age at the time of listing, have a body mass index less than or equal to 30, and have an Eastern Cooperative Oncology Group performance status of zero or one. Patients cannot have a history of significant cardiac disease.
Oncologic criteria for consideration for transplant include:
- T4a and N1c stage or less on primary tumor pathology
- No extrahepatic disease
- Carcinoembryonic Antigen (CEA) lower than 80 micrograms per liter
- Completion of six months of chemotherapy after presence of liver metastases
- Best tumor response of at least 10% on chemotherapy
- No BRAF v600E mutant
- No high microsatellite instability (MSI-H) or Lynch Syndrome
Patients must consent to receive a wide variety of liver donors and be staying within a two-hour radius of Mayo Clinic's Florida campus.
Potential candidates will undergo a standard work-up for transplant as well as an MRI of the abdomen and pelvis and a PET CT 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.