What are the MILAN (Milan Criteria) criteria for liver transplantation in patients with neuroendocrine tumor (NET) metastases?

MILAN Criteria for Liver Transplantation in Neuroendocrine Tumor Metastases

Selected patients with unresectable liver-only G1-2 neuroendocrine tumor metastases who have had the primary tumor resected, followed by a period of disease stability, may be considered for liver transplantation in centers experienced in treating neuroendocrine tumors. 1

Milan Criteria for NET Liver Metastases

The Milan criteria for neuroendocrine tumor liver metastases include:

• Primary tumor must have been resected and drained by the portal system 2, 3
• Stable disease or response to therapies for at least 6 months prior to transplantation 3, 4
• Metastatic diffusion to less than 50% of the total liver volume 2, 3
• Confirmed histology of low-grade tumor (Ki-67 <10%) 4
• Age ≤60 years 2
• Absence of extrahepatic disease 3, 4

Outcomes and Benefits

• Long-term outcomes for NET patients meeting Milan criteria who undergo liver transplantation show excellent results:

  • 5-year overall survival rates of 97.2% 3
  • 10-year overall survival rates of 88.8% 3
  • Significantly lower tumor progression rates compared to non-transplant options 3

• The transplant-related survival benefit increases over time:

  • 6.82 months at 5 years 3
  • 38.43 months at 10 years 3

Comparison with Liver Resection

• For patients with resectable NET liver metastases meeting Milan criteria, liver resection remains the first treatment option 2
• However, recent evidence suggests liver transplantation may provide superior outcomes compared to resection:
  • 10-year survival rate of 93% for transplantation vs. 75% for resection 5
  • 10-year disease-free survival rate of 52% for transplantation vs. 18% for resection 5
  • Median disease-free interval of 78 months for transplantation vs. 24 months for resection 5

Recurrence Patterns

• Recurrence patterns differ between transplantation and resection:
  • Transplant patients tend to have more multisite recurrences (48% vs. 12% in resection) 5
  • Resection patients predominantly have intrahepatic recurrences (88% vs. 8% in transplantation) 5

Considerations for Patient Selection

• Better outcomes have been reported for gastrointestinal NETs compared to pancreatic NETs for both survival and risk of recurrence after transplantation 4
• Tumor burden should be carefully assessed, as it is a key determinant of outcomes 2, 3
• Patients with G1 tumors have particularly favorable outcomes (5-year OS of 92% after resection) 2

Caveats and Limitations

• Despite promising results, few patients are completely free of tumor 5 years after liver transplantation 4
• The risk of tumor recurrence remains a significant clinical problem after transplantation 4
• Limited organ availability necessitates careful patient selection and consideration of alternative treatments 6
• There are no universally accepted strategies for prevention of recurrence or standardized follow-up protocols 4