Colorectal metastases isolated to the liver no longer portend a universally fatal outcome. In 2024, the TransMet study1demonstrated that liver transplantation in select patients could be life-saving—thus changing the treatment paradigm—but so can surgical resection when appropriately applied. Weighing these two approaches at the 2026 ASCO Gastrointestinal (GI) Cancers Symposium were Pål-Dag Line, MD, PhD, Director of the Department of Transplantation Medicine at Oslo University Hospital and Professor of Surgery at the University of Oslo in Norway, and Yuman Fong, MD, Chair of the Department of Surgery at City of Hope in Duarte, California.2,3
Liver Transplantation: Why, and in Whom?
“Liver transplantation can provide substantial treatment benefit in patients with unresectable colorectal liver disease,” said Dr. Line. “However, we have to select patients very carefully, and we have to view recurrence slightly differently than we do with other malignancies.”
He said that it is most useful to view transplantation in terms of outcome, which in this setting means survival gain with transplantation vs standard systemic therapy. In TransMet, the survival gain with transplantation was “tremendous,” he noted, citing a 5-year overall survival of 56.6% vs 12.6% with chemotherapy alone in the intention-to-treat population (hazard ratio [HR] = 0.37; P = .0003) and 73.3% vs 9.3% in the per-protocol population (HR = 0.16; P < .0001).1
Importantly, Dr. Line noted that the criteria for patient selection have been refined since TransMet was designed 10 years ago. Contemporary criteria include radical resection of the primary tumor, favorable tumor biology, disease confined to the liver, and a response to neoadjuvant chemotherapy of at least 6 months. Patients with nonmodifiable negative predictors—such as right-sided tumors, undifferentiated or signet ring cell differentiation, or N2 nodal status, as well as microsatellite instability–high tumors—are excluded. Those with BRAF V600–mutated tumors and co-mutated tumors of RAS and TP53 are usually excluded, although these factors are less relevant in patients with responses lasting at least 2 years, he said.
At his own institution, candidates must have a maximum tumor size of 5.5 cm, a carcinoembryonic antigen level of less than 80 ng/mL, a metabolic tumor volume of less than 70 cm3, and demonstrate more than a 10% reduction in tumor burden by RECIST criteria. “We have documented that, in this setting, you are looking at a 5-year survival between 75% and 80% and a 10-year survival well above 50% or 55%,” he said.
Dr. Line noted that recurrence after surgery for colorectal cancer liver metastases is common—occurring in 50% to 90% of patients—and is highly dependent on tumor volume. “That is one of the strengths of transplant,” he said: although recurrence remains common, it more often occurs in the lung. He noted recurrence rates after transplantation of approximately 60% in the lung and 3% in the liver. “The majority of lung metastases are actually resectable, and a significant proportion, if not all, are probably staging errors, so a lot of patients who recur can be offered curative-intent therapy,” he added. Curative-intent therapy for recurrence was shown to improve overall survival in TransMet and SECA-II.1,4 Pattern of recurrence and ability to provide curative-intent therapy are better indicators of treatment efficacy and overall survival than time to first relapse, he emphasized.
Is Resection of Liver Metastases More Reasonable?
“I believe that transplantation is not a solution to everything, but it’s a good solution for select patients,” Dr. Fong said. He described the advantages of surgical resection but emphasized the need for careful patient selection with this approach as well. “Whether something is resectable or nonresectable is really a judgment call. Not every case that is thought to be immediately unresectable is truly unresectable.”
Although TransMet impressed the oncology community with its outcomes, Dr. Fong reminded conference attendees that resection remains an effective treatment for most liver metastases and that enthusiasm for transplantation should be tempered, despite the TransMet data.
In TransMet, in highly selected patients who underwent liver transplantation and chemotherapy, the median overall survival was not reached, and the 5-year overall survival was 57% in the intention-to-treat population and 73% by per-protocol analysis.1 In patients from Memorial Sloan Kettering Cancer Center (MSKCC) who underwent complete resection of colorectal cancer liver metastases plus adjuvant hepatic arterial infusion (HAI) pump chemotherapy, themedian overall survival was 71 months, 5-year survival was 56%, and 10-year survival was 38% (not available for TransMet).5 While TransMet excluded patients with extrahepatic disease, the MSKCC series included them and thus represented a broader, more complex population, he noted.
“We know that control of liver disease is most important for survival, but 25% are curable with just surgery alone, even without chemotherapy. Resection is safe [< 5% mortality in most major centers] and effective. The number of tumors is no longer an absolute exclusion criterion. Chemotherapy converts nonresectable to resectable disease. Robotic resections may be done as outpatient procedures. In addition, extrahepatic disease is no longer an absolute exclusion for resection,” Dr. Fong said.
In discussions with The ASCO Post after the debate, Dr. Line wished to emphasize to readers, “The discussion of liver transplantation in the setting of colorectal liver metastasis as well as the TransMet study and our SECA studies all are about improving outcomes for selected patients with nonresectable disease, hence liver resection is not [always] an option.”
The Reality of Transplantation
Dr. Fong acknowledged, in his talk, agreeing with Dr. Line, “No doubt, if a patient is transplantable, has good-biology disease, the imaging staging says ‘go,’ and there are liver resources for this, transplantation is a good therapy,” but he said, “I want to point out that, for benign disease, liver transplantation offers 5-year survival of 80% and 10-year survival of about 70%, and therefore, for every cadaveric liver that’s given for cancer, someone else may be missing out on better survival.”
“But here’s the reality,” Dr. Fong said. He continued that the US population includes an estimated 80,000 patients with colorectal cancer metastases; about 12,000 liver transplants are performed for any type of liver disease, and of these, less than 1,000 are from living donors. “Cost is not insignificant either,” he further noted. “[It costs] about $900,000 for a transplant vs $150,000 for a resection—a difference of [nearly] a million dollars per patient when also factoring in the cost of immune suppression for transplantation. For the 50,000 resections that are actually done in America every year for various cancers in the liver, that’s a $50 billion difference.”
Dr. Line countered that while this “may to some extent be a valid point in a U.S. setting…, the costs as well as the imbalance between availability of donor organs in many countries does actually allow transplantation for a wider range of patients with malignant tumors. Extrapolating from the U.S. situation is therefore not necessarily valid for many other countries/regions.”
Although the potential complications of organ transplantation are well recognized for recipients, they can also occur in donors, Dr. Fong further noted. The donor mortality rate has been documented as 0.2%.6 Drilling down, for the approximately 9,400 livers transplanted from living donors, 6 deaths were recorded within 30 days, 3 more within 9 months, 9 within 2 years, and 61 thereafter (though details are unknown).7 “Long-term complications from donating a liver are also real,” he added.
Additional Thoughts
Dr. Fong pointed out that surgery can be curative only with low liver tumor burden; when patients have high tumor burden, liver transplantation is necessary for cure. For moderate-burden disease, he said that systemic therapies can convert patients with unresectable disease to resectable status; combination therapies and multidisciplinary care are needed. He reported generally following the treatment algorithm below, noting the last two points are the scenarios in which he sees transplantation playing a role:
- Low liver tumor burden, no extrahepatic disease: resection or ablation (needle ablation, especially for a small solitary lesion deep in the liver); systemic therapy with or without resection or ablation
- Moderate liver tumor burden, extrahepatic disease: systemic therapy with or without HAI; resection with or without systemic therapy
- Large liver tumor burden, extrahepatic disease: systemic therapy or supportive care
- Moderate liver tumor burden, no extrahepatic disease: resection plus HAI, transplantation, and possibly adjuvant systemic therapy
- Large liver tumor burden, no extrahepatic disease: transplantation and possibly adjuvant systemic therapy.
Offering a few more parting thoughts regarding the consequences of transplantation, he commented that “extrahepatic recurrence after transplant means looking for treatment in an immunosuppressed patient.” Today, this is often found in clinical trials of immunotherapy, he indicated; posttransplant patients, however, do not qualify for trials. He further emphasized that recurrence within the liver itself, after resection, can be treated with a salvage transplant. He concluded, “Resection or ablation first allows for the most rational use of cadaveric livers and live donor livers.”
Finally, he said his overriding concern is that patients with colorectal cancer and liver metastases receive timely treatment. In 2020, Dr. Fong’s group published a study establishing the “systematic failure” of colorectal cancer liver metastases resection in California. The team determined that of 154,890 cases of colorectal cancer and 77,445 cases of liver metastases, 5.5% of patients underwent resection.8 This represented a “likely missed opportunity” of more than 34,000 cases, he said—translating to a 5-year overall survival rate of 10% compared with a potential 60%, or roughly 240,000 years of life lost without resections. “I don’t want a patient waiting on a transplant list and dying on the transplant list to be a reason that someone is not given the opportunity for cure,” he said.
DISCLOSURE: Dr. Line reported no conflicts of interest. Dr. Fong reported relationships with Imugene, Medtronic, Sangamo Therapeutics, Sovato Health, and Vergent Bioscience. Viral vector technologies have been licensed to Merck and Imugene.
REFERENCES
1. Adam R, Piedvache C, Chiche L, et al: Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): Results from a multicentre, open-label, prospective, randomised controlled trial. Lancet 404:1107-1118, 2024.
2. Line P-D: For: Liver transplantation for liver metastasis. 2026 ASCO GI Cancers Symposium. Presented January 10, 2026.
3. Fong Y: Against: Liver transplantation for liver metastasis. 2026 ASCO GI Cancers Symposium. Presented January 10, 2026.
4. Dueland S, Syversveen T, Solheim JM, et al: Survival following liver transplantation for patients with nonresectable liver-only colorectal metastases. Ann Surg 271:212-218, 2020.
5. Koerkamp BG, Sadot E, Kemeny NE, et al: Perioperative hepatic arterial infusion pump chemotherapy is associated with longer survival after resection of colorectal liver metastases: A propensity score analysis. J Clin Oncol 35:1938-1944, 2017.
6. Cheah YL, Simpson MA, Pomposelli JJ, et al: Incidence of death and potentially life-threatening near-miss events in living donor hepatic lobectomy: A world-wide survey. Liver Transpl 19:499-506, 2013.
7. King EA, Hernandez-Alejandro R, Emamaullee J, et al: Over 30 years of living liver donation in North America: Mortality associated with donation. Ann Surg 282:650-657, 2025.
8. Raoof M, Jutric Z, Haye S, et al: Systematic failure to operate on colorectal cancer liver metastases in California. Cancer Med 9:6256-6267, 2020.
Belgian Study Validates TransMet Outcomes
Belgian investigators conducted a real-world study of liver transplantation for colorectal cancer liver metastases, showing that their results substantiated the positive outcomes of the landmark TransMet trial.1,2 “Our findings support further uptake of liver transplantation for unresectable colorectal cancer liver metastases. In clinical practice, they emphasize the importance of standardized national selection protocols to improve long-term outcomes, and they challenge the TransMet inclusion criteria,” said Gertjan Rasschaert, MD, of Universitair Ziekenhuis Leuven in Belgium, who presented the new findings at the 2026 ASCO Gastrointestinal (GI) Cancers Symposium.
“Liver transplantation in this specific indication gained momentum after the pivotal TransMet trial last year. At least in Belgium, we witnessed a true tsunami of referrals and questions from referring doctors and patients. In the midst of what I will call ‘chaos,’ in 2025, we established a national consensus for patient selection,” Dr. Rasschaert said. “The aim of this retrospective series was to consolidate real-world data to inform future practice and contribute to international policymaking on this emerging liver transplant indication.”
The investigators focused on all liver transplantations performed in all six accredited Belgian liver transplant centers between June 2016 and August 2025. Patient selection was guided by differing local practice. They identified 29 patients, 69% of whom were male, with a median age of 56 years. Most tumors were left-sided, all were mismatch repair–proficient, and 86% were BRAF/KRAS wild-type. The majority of metastases were synchronous presentations, and the median duration of chemotherapy was 13 months. Donor type was living donor in 34%, donation after brain death in 28%, and donation after circulatory death in 38%.
Eighteen (62%) patients had at least one adverse event of grade 3 or higher, primarily acute graft rejection (10%), biliary fistula (7%), and ascites (7%). There was one intraoperative death, and there were no retransplantations. All adverse events occurred within 30 days of transplant, and none required surgery, he reported. The three episodes of acute rejection were managed by increasing the corticosteroids.
At a median follow-up of 20.5 months, 11 (38%) patients experienced recurrence, mostly in the lung (73%) and none in the liver. Subsequent therapy was primarily systemic (73%), with some patients undergoing surgery (18%) and radiotherapy (9%). The median time to recurrence was 6.3 months, and the median overall survival afterward was 26.5 months. Posttransplant overall survival was 96.6% at 1 year and 90.1% at 2 years; recurrence-free survival was 64.8% and 54.8%, respectively, he reported.
Dr. Rasschaert noted that two patients with BRAF V600E mutations have not relapsed in more than 4 years, “which might question the exclusion criteria” for most protocols.
The Belgian Protocol
Based on the findings, the investigators established a national consensus protocol for future patient selection. It involves an independent central validation committee, like that of the TransMet trial, but is more restrictive in terms of the timing of transplantation. The protocol requires partial response and/or stable disease per RECIST criteria for at least 6 months (rather than 3 months) on the same treatment regimen. It also requires a therapeutic pause for at least 8 weeks with stable disease or liver-only progressive disease. Patients are not excluded based on point mutations (eg, BRAF) or histology.
DISCLOSURE: Dr. Rasschaert reported relationships with Merck, Ipsen, MSD, and Servier.
REFERENCES
1. Rasschaert G, Vandermeulen M, Van den Eynde M, et al: Liver transplantation for unresectable colorectal liver metastases: Pooled real-world data from all Belgian liver transplant centers. 2026 ASCO GI Cancers Symposium. Abstract 20. Presented January 10, 2026.
2. Adam R, Piedvache C, Chiche L, et al: Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): Results from a multicentre, open-label, prospective, randomised controlled trial. Lancet 404:1107-1118, 2024.
