Day two of the European Conference on Interventional Oncology (ECIO; 16–19 April, Stockholm, Sweden) opened with a session dedicated to posing and responding to the most burning questions regarding colorectal cancer (CRC) metastases. Alessandro Vitale (University of Padua, Padua, Italy) presented current advice and practice concerning bridging colorectal liver metastases (CRLM) to liver transplantation.
A “difficult” subject to tackle, Vitale first pointed out that liver transplant has gained new indications in recent years, enumerating “not only HCC [hepatocellular carcinoma],” but perihilar cholangiocarcinoma, liver metastases from neuroendocrine tumours, intrahepatic cholangiocarcinoma, and CRLM as tumours which are now among the tumours for which liver transplant can be indicated. However, Vitale proceeded to note that there is a “low” level of evidence concerning liver transplants for patients with CRLM. “Excluding case reports,” the presenter shared, “the expected long-term outcomes of liver transplants for CRLM [between 1981 and 2023] can be extrapolated from less than 100 cases”.
Data on CRLM—then versus now
He then acknowledged that there are ongoing trials across Europe, including TRANSMET out of France and SOULMATE from Sweden, the results of which are expected shortly. Vitale also mentioned his centre’s MELODIC study, which is among the same group of trials.
Before 2000, Vitale stated that it was only one team out of Vienna, Austria, to have gathered any data on liver transplant for CRLM, but that “history changed about 10 years ago” when the Norway-based Hagness et al published their paper which reported an overall survival rate at five years among 21 patients of 60%. They found “some important prognostic factors,” the speaker added, listing lesion size and progressive disease after chemotherapy among these. At 10 years, this year, Vitale informed the audience that the study had found a 42.9% overall survival rate among the original patient cohort.
In addition, Vitale underlined findings from Maspero et al published in 2023 in Cancers that suggest the main risk factors for poor prognosis post-liver transplant for CRLM patients are related to molecular biomarkers, the presence of extrahepatic disease, the size, number, and progression of the liver metastases, as well as “some parameters” relating to the primary tumour, such as it being right-sided, or it having been resected less than two years before transplant.
With this in mind, Vitale described the ideal CRLM patient candidate for transplant—they are fit, with unresectable CRLM but high tumour burden, without any extrahepatic metastases, and have a left-sided primary CRC.
Potential for expanding transplant offering
Looking to the future, the speaker mused that patients with unresectable CRLM, yet “not good” tumour biology—their disease had progressed on all standard lines of chemotherapy, or patients with single extra-hepatic metastasis—may become candidates for transplant. These patients may face “very poor outcomes” without the transplant, so the potential for benefit with transplant is “very good,” Vitale summarised. “The more interesting future transplant [CRLM] patients,” Vitale went on to say, are those whose metastases are “borderline unresectable.” If the patient is considered “borderline” for poor fitness, the presenter said they would not be good transplant candidates. However, for those who are “borderline” because the surgery would be technically complex or those whose cancer is “highly likely” to recur intrahepatically, a liver transplant may be viable in the future. Furthermore, “patients with a high tumour burden but good [oncologic] biology have an important transplant benefit,” Vitale proffered, referring to a 2021 study published in Transplant International by Lanari et al.
The role of ablation and locoregional therapies
“Ablation, now, is competitive with resection for small lesions,” the speaker averred, homing in on the interventional radiology (IR) side of bridging CRLM patients to transplant. “But there is no evidence on [its] use before liver transplantation,” Vitale lamented. “And the situation is completely different for CRLM compared to HCC,” he added, implying that one cannot directly relate the use of ablation in the latter patients to the former. “Ablation and locoregional therapy play a big role in selection for transplant and bridging to avoid dropout from the waiting list,” Vitale said of the situation with regard to HCC. On the other hand, “only systemic therapy” is used for selection and bridging for CRLM currently due to the high tumour burden in comparison to HCC. This is reflected in the guidelines, the speaker supplemented.
“A potentially important role is possible,” Vitale volunteered, speaking of ablation in bridging CRLM patients to transplant, “only if we extend our indication to initially unresectable patients with a very good response to chemotherapy.” Other potential patient demographics currently not receiving ablation to bridge to transplant are those who are oncologically borderline unresectable or technically borderline, Vitale suggested, as ablation would remove the need for challenging surgery. The same would be true of patients with repeatedly recurring CRLM—“We can choose to ablate,” the speaker asserted.
Concluding, Vitale spoke to the ethical dilemma of increasing the number of liver transplant candidates in countries where demand due to liver disease is already high. He put forward using more cadaveric livers for transplantation than is the case currently as one solution to the donor liver shortfall. On the subject of ablation as a bridge to transplant once more, Vitale conceded that it would become relevant “strictly linked to future indications, namely borderline resectable CRLM,” but with the current indications for transplant, this is not the case. From this perspective, the “transplant radiologist figure will become fundamental in the multidisciplinary evaluation of these patients.”