Can Liver Transplantation Offer Treatment? Colorectal Cancer and Liver Metastases

Colorectal cancer (CRC) is one of the most common cancers worldwide. At diagnosis, approximately 20-25% of patients have liver metastases. In addition, 50-60% of patients with CRC are at risk of developing liver metastases during the disease course. These high rates emphasize the need for effective treatment strategies for CRC that has spread to the liver.

Surgery is often impossible in CRC with liver metastases, severely limiting treatment options. Long-term survival with conventional treatment is low, and many patients receive only palliative care. However, recent studies suggest that liver transplantation may offer long-term survival and even a potential cure in carefully selected patients.

Liver transplantation has also been investigated for intrahepatic cholangiocarcinoma (cancer of the bile ducts inside the liver). Some studies have reported promising long-term survival after transplantation in these patients.

Why Liver Transplantation Rather Than Metastasectomy?

For colorectal liver metastases, the first question is whether the metastasis or metastases can be surgically removed, a procedure called liver metastasectomy. If this is impossible but removing the metastases is still considered beneficial, transplantation may be considered for liver-only disease with low recurrence scores, low metabolic tumor volume and a good chemotherapy response.

The History and Current Status of Liver Transplantation for Colorectal Metastases

Approximately 30 years ago, liver transplantation for colorectal cancer (CRC) metastases was largely abandoned because of poor survival. However, better outcomes in some patients encouraged renewed research. A study in Norway at Oslo University Hospital between 2006-2020 reported that half of 61 liver transplant recipients survived 5 years, and approximately one fifth survived 10 years.

Dr. Svein Dueland and colleagues from Oslo University Hospital's Transplant Oncology Research Group conducted the study, examining overall survival and prognostic factors. The 5-year survival rate was approximately 50.4%, and the 10-year rate was 20%. The most striking finding was that 21.7% (13 patients) had no recurrence after transplantation.

Who Can Benefit From Liver Transplantation?

The findings provide important clues for selecting suitable patients. Oslo and Fong Clinical Risk Scores (FCRS) are central to prognostic assessment. 10 patients with an Oslo score of zero had median survival of 151.6 months and approximately 89% survival at both 5 and 10 years. Those with an FCRS of 1 had median survival of 164.9 months. These data suggest that patients with low risk scores benefit more from transplantation.

In addition, on PET scans, patients with a metabolic tumor volume (PET-MTV) below 70 cm³ had nearly 67% 5-year survival, compared with 23.3% for volumes above 70 cm³. Survival was also lower with tumors larger than 5.5 cm, progression during chemotherapy, a primary tumor in the ascending colon, or nine or more liver lesions.

Liver Transplantation and New Approaches

Another study presented at the 2023 Gastrointestinal Cancers Symposium highlighted transplantation as an effective option for CRC metastases. Dr. Gonzalo Sapisochin of the University of Toronto stated that it would be effective only in liver-confined disease with an objective, sustained response to neoadjuvant treatment. He also emphasized that transplantation is not suitable for everyone and that clear inclusion and exclusion criteria must be defined beforehand.

Dr. Rafik Mark Ghobrial of Houston Methodist Hospital stated that increasing organ supply could enable more patients to benefit. Advances in hepatitis C treatment and technology are increasing the number of available livers. He reported performing 800 transplants over the previous five years, only two for hepatitis C. Donation after circulatory death has also increased, reaching 50% in some centers.

NOTE: Donation after circulatory death refers to people who die following cessation of cardiac and circulatory function and are considered suitable organ donors. Such donations help increase organ supply. Circulatory death occurs when someone cannot be revived for a specified period after cardiac arrest. In transplantation, organs are most commonly obtained from donors declared brain-dead. Brain death is irreversible cessation of all brain function; mechanical ventilation can maintain organ viability in these individuals. Both donor types are vital to transplantation and contribute substantially to organ supply.

Conclusion

Liver transplantation is emerging as a promising option for colorectal cancer metastases, potentially offering long-term survival and cure in carefully selected patients. Pioneering work by Dr. Svein Dueland and colleagues at Oslo University Hospital in Norway highlights progress and appropriate selection criteria. Limited organ supply, however, remains a major barrier to widespread use. Innovative approaches such as extended-criteria donor grafts and living-donor transplantation may increase access in the future.

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Oslo and Fong Clinical Risk Scores

These scores are important prognostic tools for treating colorectal liver metastases. They help predict long-term survival and recurrence risk.

Oslo Score

The Oslo score assesses overall survival in colorectal cancer patients undergoing liver transplantation. It is calculated from clinical and pathological factors, assigning one point for each adverse prognostic factor. The factors are:

1. Tumor Size: a large tumor (> 5.5 cm) is unfavorable.
2. Number of Liver Lesions: nine or more lesions are unfavorable.
3. Chemotherapy Response: progression during chemotherapy is unfavorable.
4. Primary Tumor Location: a primary tumor in the ascending colon is unfavorable.
5. PET-MTV (Metabolic Tumor Volume): metabolic tumor volume above 70 cm³ on PET is unfavorable.
6. Tumor Burden: a tumor burden score of 9 or higher is unfavorable.

One point is assigned for each adverse factor, and the total determines the Oslo score. Survival decreases as the score rises.

Fong Clinical Risk Score (FCRS)

The Fong score predicts recurrence risk after resection of colorectal cancer metastases. It is also based on clinical factors, assigning one point for each adverse prognostic factor. The components are:

1. Positive Lymph Nodes: positive lymph nodes at resection.
2. Short Disease-Free Interval: less than 12 months between primary tumor resection and the development of liver metastases.
3. CEA Level: carcinoembryonic antigen (CEA) above 200 ng/mL.
4. Number of Tumors: more than one liver tumor.
5. Tumor Size: the largest liver tumor measures more than 5 cm.

One point is assigned for each adverse factor, and the total determines the Fong score. Recurrence risk increases and survival decreases as the score rises.

Both scoring systems are important for treatment planning and prognostic assessment, helping identify who may benefit most from liver transplantation.