The impact of extrahepatic disease among patients undergoing liver-directed therapy for neuroendocrine liver metastasis

Introduction: Management of neuroendocrine liver metastasis (NELM) in the presence of extrahepatic disease (EHD) is controversial. We sought to examine outcomes of patients undergoing liver-directed therapy (resection, ablation, or both) for NELM in the presence of EHD using a large international cohort of patients. Methods: 612 patients who underwent liver-directed therapy were identified from eight institutions. Postoperative outcomes, as well as and overall (OS) were compared among patients with and without EHD. Results: Most primary tumors were located in the pancreas (N=254;41.8%) or the small bowel (N=188;30.9%). Patients underwent surgery alone (N=471;77.0%), ablation alone (N=15;2.5%), or a combined approach (N=126;20.6%). Patients with EHD had more high-grade tumors (EHD: 44.4% vs no EHD: 16.1%; P<0.001). EHD was often the peritoneum (N=29;41.4%) or lung (N=19;27.1%). Among 70 patients with EHD, 20.0% (N=14) underwent concurrent resection for EHD. After median follow-up of 51 months, 174 (28.4%) patients died with a median OS of 140.4 months. Patients with EHD had a shorter median OS versus patients who did not have EHD (EHD: 87 months vs no EHD: not reached; P=0.002). EHD was independently associated with an increased risk of death (HR: 2.56, 95%CI 1.16-5.62; P=0.02). Conclusion: Patients with NELM and EHD had more aggressive tumors, conferring a twofold increased risk of death. Surgical treatment of NELM among patients with EHD should be individualized.