Trends in the Management and Outcomes of Neuroendocrine Liver Metastases

OBJECTIVE: To describe the evolution of management strategies for neuroendocrine liver metastases (NE LM) and trends in patient outcomes over the preceding 3 decades. SUMMARY BACKGROUND DATA: Liver metastases are common in neuroendocrine neoplasms and impair prognosis. A broad therapeutic armamentarium has evolved over recent decades but there remains uncertainty regarding optimal treatment selection and sequencing. METHODS: Retrospective cohort study pooling data from 4 specialist centres of excellence in the United Kingdom and Germany for individuals diagnosed with neuroendocrine liver metastases between 1st Jan 1990 and 31st December 2020. We explored trends in theranostic strategies over three decades and quantified overall survival (cohort, and by decade-defined temporal periods). RESULTS: We identified 551 individuals with NE LM with a median age at diagnosis of 59.1 years; 453 (82.2%) had synchronous metastases, and 402 (73.0%) underwent multimodal therapy. In all centres somatostatin receptor-based PET/CT and MRI were the preferred imaging techniques. There were significant trends in the use of somatostatin analogues and peptide receptor radionuclide therapy but the number of surgical resections remained stable. Overall survival (OS) at 5- and 10-years was 77.5% and 58.1% respectively. Across the three time periods, 5-year OS significantly improved - period I: 45.2%, period II: 66.0%, and period III: 75.7%. Ten-year OS showed overlapping confidence intervals for Period I (23.5%) and Period II (18.3%) but doubled in period III (55.5%). On multivariate analysis, the use of multimodal therapy strategies was significantly associated with improved overall survival (HR=0.59, 95% CI: 0.40 to 0.88, P=0.009). CONCLUSIONS: Improved imaging modalities and modifications in specific therapies as components of multimodal treatment concepts are concordant with significantly improved survival outcomes in NELM over 30 years. The use of multimodal therapy improved overall survival in patients with NE LM. Future studies should determine optimal treatment selection and sequencing, and role of novel biomarkers to guide these.