Management and outcomes of patients with recurrent neuroendocrine liver metastasis after curative surgery: An international multi-institutional analysis

Objective: We sought to characterize the treatment, as well as define the long-term outcomes, of patients with recurrent neuroendocrine liver metastasis (NELM). Methods: Between 1990 and 2014, 322 patients undergoing curative intent liver surgery for NELM were identified from a multi-institutional database. Recurrences were classified as intrahepatic, extrahepatic, and both intra- and extra-hepatic. Results: Overall, median, 1-, 5-, 10-year DFS were 3.1 years, 75.5%, 40.4%, and 32.1%, respectively. After curative intent liver surgery, 209 patients (64.9%) recurred within a median follow-up of 4.5 years, while 113 (35.1%) patients were alive without disease with a follow-up time ≥3 years. The site of recurrence was intrahepatic only (n = 111, 65.7%), extrahepatic only (n = 19, 11.2%), or intra- and extra-hepatic (n = 39, 23.1%). Compared with intrahepatic only recurrence, extrahepatic only, and combined intra- and extra-hepatic recurrence were associated with a worse long-term outcome (10-year OS: intrahepatic only, 42.5%, 95%CI, 24.9-59.0 vs extrahepatic only, 0% and combined intra- and extra-hepatic, 21.5%, 95%CI, 5.3-44.0) (P < 0.001). Most patients were treated with repeat surgery (n = 49, 36.6%), while 34 (23.5%) patients received a somatostatin analogue, 27 (18.6%) systemic cytotoxic chemotherapy, and 27 (21.4%) patients had intra-arterial therapy. Ten-year OS among patients who underwent repeat surgery or intra-arterial treatments was 60.3% (95%CI, 34.1-78.8) and 52.0% (95%CI, 30.6-69.9), respectively. Patients who received somatostatin analogues (45.9% 95%CI, 22.3-66.9) or systemic chemotherapy (0%) had a shorter long-term survival (P = 0.001). Conclusion: Recurrence after surgery for NELM occurred among half of patients. Repeat liver resection for recurrence may offer a reasonable 5-year survival benefit.