Chapter 19: Liver Transplantation for Unresectable Colorectal Liver Metastases

THE CURRENT CONTEXT OF THE TREATMENT STRATEGY OF COLORECTAL LIVER METASTASES

Complete surgical resection represents the standard treatment of colorectal liver metastases (CRLM) as the only option able to achieve long-term survival (5-year survival around 40%)^1,2 and a chance of cure. However, only about 10% to 20% of patients are considered initially resectable³ and suitable for an up-front surgery. In case of unresectable CRLM, the prognosis remains poor although longer median survival of 30 months has been obtained in selected patients with good performance status (ECOG 0 to 1), no (K)RAS or BRAF mutations(4–8), and left-sided tumors4–7 but very low chance of long-term survival.

In parallel with the progress of chemotherapy, tumor shrinkage of initially unresectable CRLM has become a main objective of the treatment strategy to induce secondary resection, since complete resection in case of response offers a 33% 5-year survival.⁴ When complete surgical resection could not be achieved despite tumor response, no other therapeutic option than palliative chemotherapy could be offered, with only 10% 5-year survival, even in the case of liver-only disease.⁵ In this situation, liver transplantation (LT) was considered an attractive procedure to achieve complete resection in patients with exclusive unresectable liver disease.

THE HISTORICAL EUROPEAN EXPERIENCE (EUROPEAN LIVER TRANSPLANT REGISTRY)

Since the beginning of LT, transplant surgeons have explored the potential benefit of this procedure for CRLM. The initial results of 50 patients transplanted between 1977 and 2004 for secondary CRLM collected through the European Liver Transplant Registry (ELTR)⁶ showed a 5-year survival of only 18% (Fig. 19-1).⁷ Because of this poor long-term result, CRLM was considered an unsuitable indication to LT compared to the excellent results obtained for other indications⁸ in a period of increasing organ shortage. The analysis of this experience was interesting, however, regarding many issues.¹ In this initial experience, the vast majority of procedures were performed before 1995, a period in which LT was still considered an “experimental” procedure and postoperative mortality was still prohibitive.² At this time, the experience of centers was anecdotal concerning LT for CRLM, with 1 or 2 cases per center, except for the group in Vienna.³ Also, posttransplant immunosuppression was very potent to reduce the risk of rejection,⁴ and the absence of efficient chemotherapy protocols limited the means to reduce the risk of recurrence.⁵ Finally, graft loss was not related to tumor recurrence in 44% of cases, and despite the 18% 5-year survival, 9 of the 50 patients had a survival exceeding 5 years, 2 of whom without tumor recurrence at 9 and 21 years post-LT. Therefore, the past experience of LT for CRLM suggested that LT could obtain a potential benefit in selected patients otherwise considered for palliative chemotherapy, mirroring the survival obtained when a R0 liver resection could be achieved.