Liver Transplantation Improves Survival in Colorectal Liver Metastases

Key Points:

• For unresectable liver metastases from colorectal cancer, there is understood to be no chance of a complete cure, and palliative chemotherapy is standard treatment.
• TRANSMET is the first randomized trial to evaluate combining chemotherapy with liver transplantation for initially unresectable colorectal cancer metastatic to the liver. It shows that this approach substantially improves survival compared with chemotherapy alone.
• The findings require confirmation in a larger trial. Further research should identify which patients benefit most, particularly in countries with organ shortages.

TRANSMET findings presented at the 2024 ASCO Annual Meeting may offer a potentially more beneficial treatment to patients whose only option is palliation (Abstract 3500).

We Are Now Beginning to Discuss Liver Transplantation for Metastatic Cancer

Colorectal cancer (CRC), one of the most common cancers worldwide, is associated, in approximately 20-25% of patients at diagnosis, with liver  metastases . In addition, 50-60% of patients with CRC are at risk of developing liver metastases during the disease course. These high rates highlight the importance of 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 is low with conventional treatment, and many patients can 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.

Outcomes in trials such as TRANSMET resemble those of liver transplantation in people without cancer, suggesting that allocating organs to these patients should no longer be a problem.

Resection of liver metastases is the only treatment that can offer long-term survival and potential cure for colorectal liver metastases. Unfortunately, only 10% to 20% of patients are initially eligible for surgery.

Chemotherapy for unresectable colorectal liver metastases can make surgery possible if tumors shrink sufficiently. However, for definitively unresectable disease, palliative chemotherapy is standard, with almost no prospect of long-term survival or cure.

In the United States, two groups with unresectable colorectal liver metastases may benefit from transplantation. One has healthy livers but entirely unresectable tumors and receives transplantation based on disease burden. The other has cirrhotic livers and needs transplantation because of both tumor burden and treatment-related hepatotoxicity.

A European Trial

TRANSMET used a detailed selection process for 157 patients initially referred to a validation committee by clinics in Belgium, France and Italy. Investigators found 63 ineligible and randomized 94 between February 2016 and July 2021 to chemotherapy plus liver transplantation or chemotherapy alone. All were aged 65 or younger, had ECOG scores of 0 or 1, had unresectability confirmed by expert surgeons and had no BRAF mutation. The per-protocol analysis included 36 in the transplantation/chemotherapy group and 38 in the chemotherapy group.

5-Year Overall Survival Results

At a median follow-up of 59 months, 5-year overall survival was 57% with chemotherapy plus liver transplantation and 13% with chemotherapy alone. Median progression-free survival was 17.4 months with chemotherapy/transplantation versus 6.4 months with chemotherapy alone.

Commentary

This trial matters not only to patients but also to transplant and oncology specialists. I believe it will change the overall approach to treating unresectable colorectal liver metastases.

Its most important finding is that the survival gain from liver transplantation far exceeds what palliative chemotherapy can achieve. Although this makes transplantation attractive, 40% of referred patients were considered unsuitable, emphasizing the need to identify those who will truly benefit.

Which patients are truly suitable for liver transplantation remains an open question. Beyond that, countries with organ shortages will need to resolve how to select fairly among patients needing transplantation.

These findings suggest that current treatment approaches for unresectable colorectal liver metastases should change. However, 74% of transplant recipients experienced recurrence, particularly in the lungs, highlighting the need for further investigation.

The aim is definitive cure. Better understanding the molecular biology and microscopic disease status of patients who do not recur will help improve selection for transplantation and chemotherapy and optimize treatment.

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