Editor's Note: October 21-27, 2024, Wuhan, at the 9th Academic Symposium of the Chinese Chapter of the International Hepato-Pancreato-Biliary Association (IHPBA), we interviewed Professor René Adam, the current President of the IHPBA and a famous surgeon at AP-HP Paul Brousse Hospital in Paris, France, to share his research explorations on the use of liver transplantation combined with chemotherapy for the treatment of colorectal cancer with liver metastases (CRLM).

Q1: At this forum, you also delivered a specialized report on the topic of ‘The Role of Liver Transplantation in the Treatment of Colorectal Cancer with Liver Metastases’. Could you please introduce the core points of your report to our readers?

Prof. René Adam：This is indeed a pivotal study, primarily because it is randomized, which is rare in surgical research. What we currently know about treating colorectal liver metastases is that partial hepatic resection is the optimal therapy for patients deemed resectable. However, only 20% of patients with colorectal liver metastases present with resectable disease.

For those initially deemed unresectable, chemotherapy can sometimes downsize the tumor, allowing for secondary resection of the liver metastases and offering a significant survival benefit, with a five-year overall survival rate of approximately 30% to 40%. Yet, 50% to 60% of patients present with definitively unresectable colorectal liver metastases.

In such cases, the standard of care has been chemotherapy, which has shown remarkable advancements over the past 15 to 20 years. However, these improvements have primarily impacted short- and medium-term survival; long-term survival remains poor, with almost no chance of five-year survival.

Therefore, in this study, we compared chemotherapy combined with liver transplantation to chemotherapy alone —the previous standard of care—. The results revealed that liver transplantation plus chemotherapy significantly improves both overall survival and progression-free survival in selected patients with unresectable colorectal liver metastases compared to chemotherapy alone.

These findings were achieved through rigorous patient selection and prioritization for organ allocation. An independent selection committee was established to ensure optimal patient selection. Notably, patients who underwent transplantation for colorectal liver metastases had a five-year survival rate of 73%, compared to only 9% in the chemotherapy-alone group—a notable difference.

Furthermore, this 73% five-year survival rate is comparable to that of patients transplanted for other established transplantation indications. Importantly, liver transplantation plus chemotherapy not only adds a survival benefit but also offers a potential cure for cancer patients who otherwise have a poor long-term prognosis: in the transplantation group, 42% of patients were free of disease at 50 months of follow-up, compared to only 3% in the chemotherapy-alone group. These results are highly significant and could potentially revolutionize the treatment of patients with colorectal liver metastases.

In conclusion, these findings support the idea that liver transplantation could become a new standard option, changing our approach to treating patients with definitively unresectable colorectal liver metastases.

Q2: Based on your clinical experience, which patients with colorectal cancer and liver metastases are primarily suitable for liver transplantation? What factors do you typically consider when making treatment decisions?

Prof. René Adam：Thank you very much for your question. It is incredibly significant and crucial. The selection process is arguably one of the primary factors in achieving favorable outcomes. In our protocol, patients were required to be under the age of 65 and have liver-only metastases. It was essential that the patient’s disease was confined solely to the liver; any extrahepatic disease was a contraindication. Therefore, we focused on younger patients with liver-only disease. Another pivotal aspect was that they must respond objectively to chemotherapy.

This is a vital consideration. Patients needed to demonstrate a response to chemotherapy. Additionally, they should not have the BRAF mutation. BRAF is a gene associated with a poor prognosis, so we excluded patients with this mutation. Furthermore, patients had to have undergone chemotherapy for at least three months and up to three lines of treatment. This was a highly stringent selection process.

Moreover, the selection was conducted by a university hospital and validated by an independent expert committee including oncologists, surgeons, and radiologists. Through this rigorous process, we excluded 40% of candidates who were submitted to the validation committee. It was a very strict selection process, but it allowed us to achieve a 73% five-year survival rate.

Looking to the future, I believe that any patient with liver-only metastases who responds well to chemotherapy and is relatively young should be considered for liver transplantation.