From the Guidelines
The Milan criteria for liver transplantation in patients with hepatocellular carcinoma (HCC) state that patients are eligible for transplantation if they have either a single tumor ≤5 cm in diameter or up to three tumors, each ≤3 cm in diameter, with no evidence of vascular invasion or extrahepatic spread. These criteria were established to identify patients who would have the best post-transplant outcomes, with five-year survival rates of 70-80%, similar to patients receiving transplants for non-malignant conditions 1. The Milan criteria have become the standard benchmark for transplant eligibility worldwide, balancing the need to offer potentially curative treatment to HCC patients while ensuring appropriate allocation of scarce donor organs.
Key Points
- The Milan criteria are used to select patients with HCC who would benefit from liver transplantation
- Patients are eligible for transplantation if they have a single tumor ≤5 cm in diameter or up to three tumors, each ≤3 cm in diameter, with no evidence of vascular invasion or extrahepatic spread
- These criteria effectively balance the need to offer potentially curative treatment to HCC patients while ensuring appropriate allocation of scarce donor organs
- Patients who exceed these criteria generally have higher recurrence rates and poorer survival outcomes after transplantation
Assessment for Milan Criteria Eligibility
- Requires high-quality imaging studies, typically contrast-enhanced CT or MRI scans, performed within 1-3 months before transplant consideration to accurately determine tumor burden
- Patients with HCC beyond the transplant criteria adopted by each centre should be considered for liver transplantation after successful downstaging to within Milan criteria 1
Downstaging Strategies
- The choice of downstaging strategies should be based on patient and tumour characteristics, and no single locoregional procedure is recommended over the others
- There is insufficient evidence to recommend systemic therapy as a downstaging treatment 1
- Aggressive downstaging protocols are recommended for patients with HCC beyond Milan, as such patients have comparable outcomes to patients within Milan at presentation and better outcomes than with any other treatments 1
From the Research
Milan Criteria for Liver Transplantation in Patients with Hepatocellular Carcinoma (HCC)
The Milan criteria are a set of guidelines used to determine whether patients with HCC are eligible for liver transplantation. The criteria are as follows:
- A single tumor up to 5 cm in size
- Up to 3 tumors, each up to 3 cm in size
Rationale and Outcomes
Studies have shown that patients who meet the Milan criteria have favorable outcomes after liver transplantation. For example, a study published in 2007 found that patients with a single tumor ≤5 cm or 2-3 lesions all ≤3 cm in diameter had a recurrence-free survival rate of 84.7% at 1 year and 61.8% at 5 years 2. Another study published in 2008 reported that patients who received transplants within the Milan criteria had actuarial survival rates of 85.9%, 74.8%, and 64.1% at 1,3, and 5 years, respectively 3.
Expanded Criteria and Alternative Models
In recent years, there has been a trend towards expanding the Milan criteria to include patients with more advanced tumors. Some studies have proposed alternative models that take into account additional factors such as alpha-fetoprotein levels, tumor size, and number of nodules 4, 5. These models have been shown to outperform the Milan criteria in identifying patients with low risk of HCC recurrence or those who will survive for 5 years after liver transplantation.
Current Practice and Future Directions
Despite the potential benefits of expanding the Milan criteria, the current practice in many Western countries is still to select patients based on these criteria. However, there is a growing recognition of the need to reconsider the Milan criteria and to develop more personalized and effective selection strategies for patients with HCC 6. Further research is needed to determine the optimal criteria for selecting patients with HCC for liver transplantation and to improve outcomes for this patient population. Key points to consider include:
- The Milan criteria may be too restrictive and could be expanded to include patients with more advanced tumors
- Alternative models that take into account additional factors such as alpha-fetoprotein levels and tumor biology may be more effective in identifying patients with low risk of HCC recurrence
- The development of new treatment modalities and downstaging strategies has enabled more patients with HCC to be considered for liver transplantation
- Further research is needed to determine the optimal criteria for selecting patients with HCC for liver transplantation and to improve outcomes for this patient population 2, 3, 4, 5, 6