Why liver transplant is back in the NET conversation

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1. Big picture: why liver transplant (LT) is back in the NET conversation

• Rationale: For a very small, highly selected subset of patients with unresectable liver-only or liver-dominant metastases from well-differentiated NETs, LT can offer long-term disease control or potential cure when other options are exhausted or insufficient.
• Shift in tone: Historically poor outcomes (early days of LT) made most centres very cautious. More recent series using strict criteria (e.g. Milan criteria) have shown much better survival, prompting ENETS, UNOS and national groups to formally recognise LT as a valid but rare indication.

2. Europe/UK: current initiatives and pilot programmes

2.1 UK & Ireland national pilot programme

• Programme: UK & Ireland National Pilot Programme of Liver Transplantation in Neuroendocrine Patients with Liver Metastases (NET LM), endorsed by NHS Blood and Transplant and guided by a national expert panel.
• Scale: Planned for around 50 patients over ~5 years, functioning as a prospective, case-controlled pilot to generate robust outcome data.
• Governance:
  • Central virtual national MDT (nMDT) meets monthly.
  • Referrals from NET specialist teams using a standard proforma.
  • nMDT advises on eligibility, further work-up, and referral to linked liver transplant centres.

2.2 Early pilot data (UK & Ireland)

• Timeframe: August 2021–April 2024.
• Activity:
  • 36 patients considered appropriate for the liver transplant pathway.
  • 5 patients transplanted, 2 listed, 4 in assessment, 9 potentially appropriate pending further results.
  • 11 centres have referred patients; some patients opted out.
• Purpose: Build a national database, tissue/blood banking and a research platform for trials and longitudinal cohorts in NET LT.

2.3 European context

• ENETS position: ENETS recognises LT as a valid option for grades 1–2 well-differentiated NETs with unresectable liver metastases in highly selected cases, generally aligned with Milan-type criteria.
• Practice pattern: Still rarely used across Europe; mostly concentrated in a few high-volume transplant/NET centres, often within research or structured programmes rather than routine practice.

3. United States: current stance and initiatives

• UNOS/OPTN recognition: LT for NET liver metastases is an accepted but uncommon indication; centres may apply for MELD exception points for carefully selected NET patients, often referencing Milan-type criteria and published series.
• Model of care:
  • No single national “pilot” like the UK, but centre-led programmes in major transplant/NET hubs.
  • Use of strict selection criteria, multidisciplinary review, and often inclusion in institutional or multi-centre registries.
• Trend: Growing interest, but constrained by organ scarcity, ethical considerations, and the need to show clear survival and quality-of-life benefit versus non-transplant options.

4. Patient selection criteria (Milan-type and UK pilot)

Most programmes now converge on Milan criteria or close variants. The UK & Ireland pilot explicitly bases its selection on the Milan group’s criteria.

4.1 Core biological and pathological criteria

• Tumour grade:
  • Well-differentiated NET, Grade 1 or Grade 2 (Ki-67 usually ≤10%, sometimes ≤20% depending on protocol).
• Primary site:
  • Gastro-entero-pancreatic (GEP) origin (small bowel, pancreas, etc.).
  • Primary tumour resected (and regional lymph nodes addressed) before LT, or at least clearly resectable with intent for complete clearance.

4.2 Disease distribution and burden

• Liver involvement:
  • <50% of liver volume involved by metastases in the UK pilot.
• Extrahepatic disease:
  • No uncontrolled extrahepatic disease; any extrahepatic sites must be resectable/eradicated or absent. (This is a key Milan principle, even if phrased slightly differently across centres.)

4.3 Disease behaviour and stability

• Stability:
  • Stable disease or response to therapy for at least 6–12 months prior to transplant consideration (UK pilot uses ≥6 months).
• No high-grade transformation:
  • No evidence of progression to poorly differentiated NEC or high-grade biology.

4.4 Patient-related criteria

• Age:
  • UK pilot uses <60 years as a relative criterion (younger patients generally preferred).
• Performance status:
  • Good functional status (e.g. ECOG 0–1), adequate cardiopulmonary reserve.
• Comorbidities:
  • No major contraindications to major surgery or lifelong immunosuppression.

5. Summary

• “Liver transplant is not a standard treatment for most people with NETs.”
• “In a very small group of people—usually younger, with slow-growing, well-differentiated NETs where the cancer is mainly in the liver and has been stable for some time—liver transplant may be considered in specialist centres.”
• “In the UK and Ireland, this is currently being studied in a national pilot programme, with strict rules about who can be referred. Decisions are made by a national expert panel, not by one doctor alone.”
• “In Europe and the US, expert groups recognise liver transplant as an option in carefully chosen cases, but it remains rare because donor livers are limited and other treatments can control the disease for many years.”

 

🌍 Latest Updates on Liver Transplantation for NETs (mainly UK/Ireland, Europe, USA)

6. References (any available links will be in blue):

UK & Ireland: Latest Updates (2024–2025)

1. Updated National Guidance (Nov 2024 Edition V2.1)

The UK & Ireland programme released a major updated guidance document in November 2024, confirming:

• Continued use of Milan criteria for Phase I, with planned expansion in Phase II.
• Target: 50 patients in the service evaluation.
• National Advisory Board established to oversee consistency and governance.
• 1‑year survival target >60% (equivalent to 50% 5‑year survival) as a success benchmark.

2. Updated Pilot Data (2025 UKINETS Conference)

As of July 2025:

• 56 referrals from 18 centres
• 9 suitable, 25 potentially suitable, 22 not suitable
• 8 patients transplanted (all under follow‑up)
• Age range of transplanted patients: 44–64
• All were Grade 1–2, mostly GI primaries

3. Earlier 2024 Progress Report (Gut Journal)

From August 2021–April 2024:

• 36 patients considered appropriate
• 5 transplanted, 2 listed, 4 in assessment
• 11 centres referring

Rest of Europe: Latest Developments

1. ENETS Position (2024–2026)

ENETS continues to recognise liver transplantation as a valid option for G1–G2 well‑differentiated NETs with unresectable liver metastases, aligned with Milan criteria.

• ENETS 2024–2026 publications emphasise structured pathways, multidisciplinary evaluation, and harmonisation across European Centres of Excellence.

2. European Expert Review (2023, still current)

A major review summarises:

• LT for NET LM is now accepted by ENETS and UNOS.
• Still rarely used, but evidence supports benefit in highly selected patients.
• UK/Ireland pilot highlighted as a model for structured national programmes.

United States: Latest Updates (2024–2025)

1. Major Policy Change: MELD Exception Points for NETs (2024–2025)

In July 2024, the National Liver Review Board (NRLB) introduced non‑standard exception points for:

• Metastatic neuroendocrine tumours
• Colorectal liver metastases
• Intrahepatic cholangiocarcinoma
• Hepatic epithelioid hemangioendothelioma

In July 2025, these were codified into OPTN allocation policy as standardised exception pathways — a major shift that formally recognises NET LM as a transplant‑eligible indication under defined criteria.

2. OPTN/NLRB Guidance (Dec 2025)

The OPTN issued detailed guidance for MELD exceptions in hepatic neoplasms, including neuroendocrine tumours, to standardise review and ensure consistent national decision‑making.

3. US Clinical Perspective (2025 Review)

A 2025 review confirms:

• OLT offers meaningful survival benefit in carefully selected NET LM patients.
• Reinforces importance of Milan‑NET criteria and multidisciplinary evaluation.

Disclaimer

I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me.

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Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

Thanks for reading.

Ronny

 

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