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Aims and potential for liver transplantation in patients with neuroendocrine tumours:

There is now good evidence that patients receiving liver transplantation within the ‘Milan Patient Selection Criteria for Neuroendocrine Tumours’ have improved survival outcomes. Although liver transplantation for neuroendocrine tumour liver metastases is an accepted form of treatment in most countries, only in the United Kingdom and the Republic of Ireland do we have a formal programme to develop, promote and fairly apply this treatment. Furthermore, the national panel of specialists that come together every month to help select patients have become the foremost experts in the field. This expertise is now helping identify new opportunities for the use of liver transplantation, beyond the Milan Criteria, in helping more patients with neuroendocrine tumours.

Ultimately, this programme is helping to constantly move forward both the fields of liver transplantation and its life prolonging application to patients with neuroendocrine tumours.

Background:

As patients and their healthcare professionals are all aware, neuroendocrine tumours can start anywhere in the body. They tend to involve the local lymph nodes first before spreading to more distant areas of the body, usually the more distant lymph nodes and the liver. The chest area and the bones may also become involved.

Although we are now diagnosing more patients with early-stage cancer when surgery may be curative, a great proportion of patients still have disease that has spread to distal areas by the time of diagnosis.

When the specialist teams are planning treatments for patients, they always consider the possibility of surgery to remove most, if not all, of the cancer provided it can be done safely and would lead to improved outcomes in terms of survival and quality of life. In general, surgery is feasible in 10-20% of patients (1 in 10 or 2 in 10 patients).  The majority of patients are either monitored without any cancer treatment or given ‘medical’ treatments such as Octreotide, Lanreotide or Everolimus, for example.

Surgery on the liver is possible when there are a limited number of areas affected by the cancer such that enough normal liver can be kept ensuring good patient health.

Usually, the tumours  in the liver are widespread, such that surgery to safely remove a significant amount of tumour is not possible. In patients with limited tumour outside the liver, consisting of the primary and nearby lymph nodes, it may be possible to consider liver transplantation, after successful removal of the primary and nearest lymph nodes, in order to try to provide a ‘cure’.

For patients potentially suitable for liver transplantation, we must bear in mind that for many the prognosis will be excellent without liver transplantation; for some it will not be a safe undertaking; whilst for others it may significantly improve life expectancy and the quality of life.

Since 2019, we have developed a national programme for liver transplantation for UK and Irish patients with neuroendocrine tumours.

We created a national panel of experts in neuroendocrine tumours and liver transplantation in order to provide the highest quality of decisions for each patient.

To date, we have assessed 74 patients and 12 have undergone liver transplantation. Some patients are still going through the transplant pathway, some do not need transplantation due to their excellent prognosis with standard treatments, some have decided against transplantation, and some are not suitable for transplantation due to poor overall health or due to the presence of tumours outside of the liver despite surgery to remove the primary.

Milan Criteria

We started by selecting patients for liver transplantation based on the internationally recognised Milan Criteria for neuroendocrine tumour liver metastases (Table 1). After an initial phase of 10 transplants, we modified the criteria taking into consideration additional evidence for the types of patients that would benefit from liver transplantation as well as the experience of the national panel from overseeing the outcomes in patients that were discussed at the national MDT meeting. A revised patient selection criteria was then proposed and has been accepted by the NHS Blood and Transplant authority and the Liver Advisory Group (Table 1 – expanded UK&I criteria). This will hopefully allow us to include more patients.

Expectations:  

Even though neuroendocrine tumours are slow-growing, with thankfully most patients living long and productive lives, there is nevertheless a pressing need to find ways of restoring normal life expectancy when it is compromised.

As can be seen by the testimonials from patients who have undergone the procedure, liver transplantation is challenging for all involved. However, it is an excellent way of achieving cure and prolonged survival that would mean a normal life expectancy in most transplant recipients. The overall feedback from these patients has been generally positive.

The expectations with this programme have been to:

• Raise knowledge of the role of liver transplantation amongst experts and patients

• Set up a programme that delivers fair, safe, appropriate, and equitable treatments

• Provide evidence for safety and effectiveness of liver transplantation in patients with neuroendocrine tumours

• Provide guidance on safely expanding patient selection criteria so that an increasing number of patients with neuroendocrine tumours can be helped

 

Challenges:

The patient stories point out several challenges with this programme.

Early on, the professionals involved were reluctant to provide strong advice and reassurance of the likely benefits of liver transplantation. This placed a fair amount of the decision-making burden on the patients. Although we can now be more reassuring, patient counselling remains challenging.

As pointed out by some, the benefits of liver transplantation are often not obvious to patients with neuroendocrine tumours since their livers function well and there are no features of liver failure. The survival benefits accrue in the long-term, starting about five years after the transplant, meaning the risks are front loaded while the benefits are delayed.

Better ways of explaining these issues to patients need to be devised. Better psychological support is needed for patients to help cope with the stress and anxiety of going through the transplant process.

Concept of liver transplantation is difficult for most professionals to comprehend since the neuroendocrine experts are not knowledgeable of liver transplantation and the liver transplant teams are not knowledgeable of neuroendocrine tumours.

The national MDT meeting, conferences and webinars have been used to bring the two groups of experts together to improve understanding and access to liver transplantation for patients with neuroendocrine tumours.

Another challenge has been the relative scarcity of livers for transplantation. The need for livers is greater than the donated organs available. We are trying to overcome this in UK by developing living donor liver transplantation where a relative can donate a part of their liver for transplantation.

Rewards:

Seeing 12 patients receive liver transplants successfully has been a big relief for all involved. Patients have been generally pleased with their transplants and those with carcinoid syndrome describe significant improvement in their medication requirements and bowel-related health.

The national MDT is now the most experienced in assessing patients for the likely benefits of liver transplantation. It can guide neuroendocrine tumour specialists and their patients on prognosis with or without transplantation.

The national MDT meeting has become the best teaching environment for the management of patients with neuroendocrine tumour liver metastases.

Conclusion:

The national programme has given us a clear start in trying to find cures for many more patients with neuroendocrine tumours.

We intend to continue developing the transplant programme to help increasing number of patients through liver transplantation. Continued effort to improve understanding and growing technical knowledge will help deliver on this aim.

Table 1: Updated and expanded UK and Ireland selection criteria for liver transplantation in patients with neuroendocrine tumour liver metastases. Phase II criteria incorporate the February 2026 LAG report and require individual national MDT approval.

Liver Transplant for NET Liver Metastases Pilot Programme	Phase I ‘Milan Criteria’: [1–10 liver transplants] — completed	Phase II ‘Expanded UK&I Criteria’: [11–50 liver transplants]
Histology	Grade 1/Grade 2 Well Differentiated NET	Grade 1/Grade 2 Well Differentiated NET
Primary site	GEP (bowel and pancreas) NET	GEP (bowel and pancreas) NET + selected other primaries (e.g. lung, ovary, renal)
Primary and associated lymph nodes	Completely resected before liver transplant surgery	Normally resected before LT. Resection during or after LT only in exceptional cases. Small residual nodal disease (e.g. mesentery or a single distal site) requires individual national MDT approval on adequate transplant benefit.
Liver metastatic burden	Less than 50% by volume	Up to 80% by volume and/or hepatomegaly (liver enlargement)
Disease stability	Stable disease and/or response to therapies for at least 6 months prior to transplant consideration	Stable disease and/or response to therapies for at least 6 months prior to transplant consideration
Patient age	< 60 (relative criteria)	National MDT recommendation based on transplant benefit irrespective of age

October 2026