Colorectal cancer is the third most commonly diagnosed cancer in the world and the second leading cause of cancer-related deaths, with approximately 1.23 million new cases each year. While survival rates are high for localized disease - approaching 91% at five years - they drop sharply once the cancer has spread. Patients with distant metastases have a five-year survival rate of only about 14%.
The liver is the most common site where colorectal cancer spreads, largely because blood from the colon and rectum drains directly through the portal vein to the liver. Synchronous colorectal liver metastases (CRLMs) - meaning metastases present at the same time as the primary tumor - are found in 20 to 25% of patients at diagnosis. A further 30% develop liver spread after their initial treatment.
Surgery remains the only treatment with potential to cure liver metastases, offering roughly 38% survival at five years and 26% at ten years. However, only about 20% of patients with liver metastases are eligible for surgery at the time of diagnosis. The remaining 80% face a prognosis of less than 10% survival at five years, making the search for alternative treatments critically important.
For many decades, liver transplantation (LT) was considered inappropriate for colorectal cancer patients because of concerns about cancer recurrence after immunosuppressive therapy. However, pioneering work from Norway demonstrated that carefully chosen patients with unresectable colorectal liver metastases could achieve surprisingly good outcomes after transplantation, reigniting interest in this approach.
A landmark randomized controlled trial (the TransMet trial) reported that patients who received liver transplantation achieved a five-year overall survival of 57%, compared to only 13% in patients treated with chemotherapy alone. This striking difference suggests that transplantation may represent a transformative option for patients who have exhausted standard therapies.
Advances in living donor liver transplantation (LDLT), machine perfusion technologies for organ preservation, and better patient selection tools have made this approach more feasible. At the same time, important questions remain about which patients are most likely to benefit, how to allocate scarce donor organs ethically, and how transplantation compares to other liver-focused treatments.
This study followed the PRISMA 2020 guidelines - an internationally recognized framework for conducting and reporting systematic reviews - and was registered in the PROSPERO database before data collection began. The review searched ten major electronic databases, including PubMed, MEDLINE, Embase, Cochrane Library, Scopus, and others, covering studies published between November 2015 and November 2025.
To be included, studies had to focus on adult patients with unresectable colorectal liver metastases who had failed or were not suitable for standard treatments, and who received liver transplantation as the primary treatment approach. A wide range of study designs was accepted, including randomized trials, cohort studies, case series, and registry analyses, to capture as much evidence as possible from this relatively new and rare field.
Data extraction was performed by two independent reviewers using a standardized form, with a third reviewer resolving any disagreements. The extracted information included patient characteristics, tumor features, pre-transplant treatments, and outcomes. In total, 23 studies involving 540 patients were included, comprising both deceased donor and living donor transplants across multiple countries and institutions.
Quality assessment was performed using the ROBINS-I tool (Risk of Bias in Non-randomized Studies of Interventions), which evaluates seven potential sources of bias. Because all but one included study was non-randomized, this tool was the most appropriate instrument for evaluating methodological quality across the evidence base.
The most important source of bias was confounding: patients selected for transplantation were already a highly filtered group based on tumor biology, response to chemotherapy, and institutional criteria. This means transplant recipients were not representative of all patients with liver metastases - they were the best candidates - which makes it difficult to directly compare outcomes to non-transplant patients.
Statistical analyses used random-effects meta-analysis models to pool survival rates, disease-free survival, and recurrence rates across studies. This approach accounts for the expected variability between studies. Heterogeneity - how much variation existed between study results - was quantified using the I2 statistic, where values above 75% indicate substantial differences between studies that must be interpreted with caution.
The pooled overall survival rates after liver transplantation for unresectable colorectal liver metastases were remarkably favorable: 96.6% at one year, 73.4% at three years, and 49.4% at five years. At ten years, survival was approximately 27%. For comparison, patients with unresectable liver metastases who receive chemotherapy alone typically have less than 10% five-year survival.
These survival estimates came with notable heterogeneity between studies - the I2 values for three-year and five-year survival exceeded 90%, meaning results varied considerably across institutions and patient populations. This variation likely reflects differences in patient selection criteria, transplant techniques, and the evolution of this approach over the study period, as earlier cohorts often included higher-risk patients.
The randomized TransMet trial, the most rigorous evidence source included in this review, confirmed a five-year overall survival of 57% in the transplant group versus 13% in chemotherapy-only patients. This head-to-head comparison provides the strongest evidence that transplantation offers a meaningful survival benefit over systemic therapy alone in properly selected patients.
Despite encouraging overall survival rates, cancer recurrence remained common after liver transplantation. The pooled recurrence rate was 63.5% (95% CI: 52.5 to 76.8%). This means that nearly two-thirds of transplanted patients experienced cancer returning at some point after their procedure - a rate substantially higher than recurrence following transplantation for other cancers such as hepatocellular carcinoma.
Importantly, most recurrences occurred outside the liver - most commonly in the lungs. This pattern of extrahepatic recurrence is different from what is seen after liver resection for colorectal metastases, where recurrence often returns to the liver. The shift toward pulmonary and other distant sites after transplantation may reflect the fact that liver disease is definitively treated, but microscopic disease elsewhere can later become apparent.
Disease-free survival - the time without any evidence of cancer - was 64.1% (95% CI: 47.5 to 80.7%), again with very high heterogeneity between studies (I2 = 95.6%). Despite frequent recurrence, the fact that many patients continued to survive for years after recurrence detection suggests that some patients have biologically favorable disease that grows slowly even after transplantation, and that post-recurrence treatments can provide additional benefit.
One of the most consistent findings across studies was that tumor biology predicted outcomes better than tumor burden. Patients with smaller or fewer metastases did not always do better than those with extensive liver involvement. Instead, biological markers reflecting the cancer's behavior and aggressiveness were more predictive of long-term survival.
Carcinoembryonic antigen (CEA) levels measured before transplantation consistently emerged as a strong prognostic factor. CEA is a protein that some colorectal cancers release into the blood, and elevated levels suggest more aggressive disease. Studies used various thresholds, but CEA levels above 80 micrograms per liter were generally associated with worse outcomes. Patients with low pre-transplant CEA - indicating biologically favorable disease - were the best candidates.
Other important selection tools included the Oslo score (a composite score based on tumor characteristics and CEA that was developed specifically for transplant candidacy), the Fong Clinical Risk Score, and metabolic tumor volume (MTV) measured on FDG-PET scans. Patients with low Oslo scores and low MTV consistently achieved better outcomes. These tools highlight that the best transplant candidates are those whose tumors show favorable biology - stable or responding disease, low metabolic activity, and low circulating biomarker levels.
Liver transplantation for colorectal liver metastases is considered only after conventional treatments have failed. Virtually all patients included in this review had received systemic chemotherapy before transplantation, typically using fluoropyrimidine-based regimens such as FOLFOX or FOLFIRI, often combined with biologic agents such as bevacizumab or cetuximab. Most patients had received at least two lines of chemotherapy.
Resection of the primary colorectal tumor was performed in essentially all patients before transplantation. This represents a fundamental prerequisite - patients must have their colon or rectal cancer surgically removed before being considered for liver transplantation. Many also underwent liver-directed procedures such as radiofrequency ablation or partial liver resection as part of their treatment history.
A key eligibility requirement across most programs was demonstration of stable or responding disease on systemic therapy - that is, the cancer should not be actively progressing at the time of transplantation. Good physical performance status (ECOG score 0 to 1) was also universally required. These criteria ensure that the patient is healthy enough for the major surgery and that the cancer is behaving in a biologically favorable way.
One of the most important constraints on using liver transplantation for colorectal metastases is the global shortage of donor organs. Donor livers are a scarce resource, and thousands of patients with end-stage liver disease from other causes - such as cirrhosis, hepatitis, or alcoholic liver disease - are waiting for transplants. Allocating organs to cancer patients raises ethical questions about fairness and how to balance competing needs.
Living donor liver transplantation (LDLT) offers a potential solution to this ethical dilemma. In LDLT, a healthy volunteer (typically a family member) donates a portion of their liver, which regenerates over time in both donor and recipient. This approach does not reduce the pool of deceased donor organs available for other patients. Several of the studies included in this review used LDLT specifically for this reason, and outcomes in LDLT recipients were comparable to those receiving deceased donor grafts.
The ethical framework for these decisions continues to evolve. Most transplant centers require patients to undergo careful multidisciplinary evaluation and have their cases reviewed by ethics committees. The availability of rigorous selection criteria, emerging evidence from randomized trials, and the potential to use living donors all contribute to a growing consensus that transplantation can be ethically justified in carefully selected patients at specialized centers with appropriate governance.
This systematic review and meta-analysis demonstrates that, in highly selected patients with unresectable colorectal liver metastases, liver transplantation can achieve five-year overall survival of approximately 49%, far exceeding the less than 10% expected with continued systemic therapy alone. The randomized TransMet trial confirms a survival benefit of 57% versus 13% at five years compared to chemotherapy, providing high-quality evidence supporting this approach.
However, the authors emphasize that this remains an investigational approach. The evidence base consists primarily of small, single-center studies with high methodological heterogeneity, moderate to high risk of bias, and highly selective patient populations that may not be generalizable. Further prospective randomized trials with standardized selection protocols are urgently needed to clarify which patients benefit most and to determine the optimal timing of transplantation relative to other treatments.
The future of this field will depend on developing better biological selection criteria, expanding access to living donor programs, and integrating new imaging tools such as metabolic tumor volume by FDG-PET into standardized decision-making frameworks. As evidence accumulates, liver transplantation for colorectal liver metastases may transition from an experimental last resort to an established component of multidisciplinary cancer care at specialized centers worldwide.