Liver Transplant Offers Durable Survival in NET Liver Metastases Despite Recurrence

Liver transplantation provided durable long-term survival for highly selected patients with unresectable neuroendocrine liver metastases (NELM), with more than 40% of patients alive at 10 years, although most patients eventually experienced recurrence. Tumor burden emerged as the strongest predictor of outcome, according to a 25-year retrospective analysis from 3 Mayo Clinic sites presented by Joseph Kim, MD, PhD, of Mayo Clinic Florida, at the 2026 North American Neuroendocrine Tumor Society (NANETS) Symposium.¹

Among 47 patients who underwent liver transplant, overall survival (OS) was 81.8% at 3 years, 74.3% at 5 years, and 44.3% at 10 years, with a median OS of approximately 9 years. Disease-free survival (DFS) was lower, at 57.6%, 49.9%, and 20.1%, respectively, with a median DFS of approximately 4 years. At 10 years, roughly 1 in 5 patients were alive without recurrence, and about 1 in 4 were alive with recurrent disease.

Kim summarized the findings as evidence that transplant offers durable control rather than cure for most patients.

OPTN Criteria Identified Patients With the Best Outcomes

The investigators classified each patient according to whether they met the Organ Procurement and Transplantation Network (OPTN) criteria used to grant Model for End-Stage Liver Disease (MELD) exceptions for NELM. Overall, 25 patients (53%) met the criteria and 22 did not.

Patients who met OPTN criteria had markedly better outcomes. The 10-year OS rate was 61% among those who met the criteria vs 26% among those who did not (HR, 0.37; 95% CI, 0.17-0.80; P = .012), and the 10-year DFS rate was 30% vs 10%, respectively (HR, 0.35; 95% CI, 0.18-0.70; P = .003).

Tumor Burden Drives Risk

In univariable analyses, 2 factors defined a high-risk group. Patients whose tumors replaced more than 50% of the liver on imaging had more than 3 times the risk of death (HR, 3.75; 95% CI, 1.71-8.23) and 4 times the risk of recurrence or death (HR, 4.01; 95% CI, 1.85-8.70) compared with those with lower tumor burden. Disease progression within 3 months before transplant was also associated with worse OS (HR, 2.53; 95% CI, 1.10-5.83) and DFS (HR, 2.17; 95% CI, 1.03-4.57).

After multivariable adjustment, tumor replacement greater than 50% remained independently associated with both worse OS and DFS, with adjusted HRs of about 3. Pretransplant progression remained associated with worse OS but not DFS. Tumor grade 1 vs grade 2 or 3 was not significantly associated with outcomes after adjustment, and during the question-and-answer session, Kim noted that Ki-67 index did not appear to play a major role in their analyses.

Notably, the protective association of meeting OPTN criteria weakened once tumor burden was accounted for, with the adjusted HR for OS moving from 0.37 to 0.61 (P = .27), although the effect still trended in a protective direction.

“In other words, much of what the criteria [capture] seems to be [tumor replacement over 50%],” Kim said, referring to the OPTN requirement that tumor replacement not exceed 50% of total liver volume.

Recurrence Is Common, Late, and Often Treatable

Recurrence was the main limitation of transplant. Overall, 31 of 47 patients (66%) experienced recurrence, at a median of 2.3 years after transplant, and recurrences often appeared late, underscoring the need for long-term follow-up. Recurrence was usually multifocal, with 19 of 31 patients having disease at more than 1 site. The most common sites were lymph nodes, bone, and the transplanted liver, with less frequent involvement of the lung, brain, pancreas, muscle, and stomach.

“But recurrence is not the end of the story,” Kim said.

Median survival after recurrence was 4.2 years, and 84%, 57%, and 39% of patients were alive at 1, 3, and 5 years after recurrence, respectively. Of the 26 patients who received treatment after recurrence, most received somatostatin analogues, and others received radiation, peptide receptor radionuclide therapy, or chemotherapy or targeted therapy. The investigators also recommended the use of somatostatin receptor PET imaging in this setting.

Study Design and Rationale

The liver is the dominant site of metastasis in NETs, and because liver metastases are often multifocal and bilobar, unresectable disease is not uncommon. Liver transplant has therefore been explored as an option for these patients. In a landmark study of patients meeting Milan criteria, 10-year OS was 88.8% with transplant vs 22.4% without,² and later series have favored transplant over resection within Milan-type criteria. International consensus recommendations have also addressed the role of transplant in carefully selected patients with NELM.³

In the United States, patients with NELM are eligible for a MELD exception based on OPTN criteria, making patient selection particularly important.⁴ The criteria applied in this study included age younger than 60 years; resection of the primary tumor and any extrahepatic disease; no evidence of recurrence for at least 6 months before the exception request; metastases limited to the liver, bilobar, and not amenable to resection; gastroenteropancreatic origin; low or intermediate tumor grade; tumor replacement not exceeding 50% of total liver volume; and a negative metastatic workup. Kim noted that the age criterion was later dropped in updated OPTN guidance but was applied in this analysis.

The retrospective study included adults with unresectable NELM who underwent liver transplant at Mayo Clinic sites in Arizona, Florida, and Minnesota between 1998 and 2026. The median age was 48 years, and the primary tumor was in the pancreas in 23 patients and the small bowel in 22. About one-third of patients had tumor replacement greater than 50%, and about one-third had progression within 3 months before transplant. Median follow-up among survivors was 100.7 months. End points were OS and DFS from the time of transplant, analyzed with Kaplan-Meier methods and univariable and multivariable Cox models.

Kim acknowledged that the study involved very highly selected patients and was retrospective, with no control group. Next steps include refining selection around tumor burden and pretransplant progression, multicenter validation, and prospective trials of neoadjuvant and adjuvant strategies.

“We should tell [patients] that about two-thirds of the patients will eventually recur,” Kim said. “And recurrence is not the end of the story.”

References

1. Kim J. Long-term outcomes of liver transplantation for neuroendocrine liver metastases: the Mayo Clinic experience. Presented at: 2026 North American Neuroendocrine Tumor Society (NANETS) Symposium; November 5-7, 2026; Las Vegas, NV.

2. Mazzaferro V, Sposito C, Coppa J, et al. The long-term benefit of liver transplantation for hepatic metastases from neuroendocrine tumors. Am J Transplant. 2016;16(10):2892-2902. doi:10.1111/ajt.13831

3. Frilling A, Modlin IM, Kidd M, et al. Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol. 2014;15(1):e8-e21. doi:10.1016/S1470-2045(13)70362-0

4. National Liver Review Board guidance: adult transplant oncology. Organ Procurement and Transplantation Network. February 2025. Accessed November 7, 2026.