Carlo Pulitano, Scott A. Celinksi, Jennifer Strub, Giles Mentha, Carrie K. Chu, Timothy M. Pawlik, Michael A. Choti, Brian M. Clary, Jayme B. Stokes, Reid B. Adams, Charles A. Staley, Alessandro Ferrero, Srinevas K. Reddy, David A. Kooby, Skye C. Mayo, Lorenzo Capussotti, Mechteld C. de Jong, Luca Aldrighetti, Richard D. Schulick, T. Clark Gamblin, Todd W. Bauer, Mayo Skye, C., de Jong Mechteld, C., Pulitano, Carlo, Clary Brian, M., Reddy Srinevas, K., Gamblin T., Clark, Celinksi Scott, A., Kooby David, A., Staley Charles, A., Stokes Jayme, B., Chu Carrie, K., Ferrero, Alessandro, Schulick Richard, D., Choti Michael, A., Mentha, Gile, Strub, Jennifer, Bauer Todd, W., Adams Reid, B., Aldrighetti, L, Capussotti, Lorenzo, and Pawlik Timothy, M.
BACKGROUND: Management of neuroendocrine tumor liver metastasis (NELM) remains controversial, with some advocating an aggressive surgical approach while others have adopted a more conservative strategy. We sought to define the efficacy of the surgical management of NELM in a large multicenter international cohort of patients. METHODS: We identified 339 patients who underwent surgical management for NELM from 1985 to 2009 from an international database of eight major hepatobiliary centers. Relevant clinicopathologic data were assessed using Kaplan-Meier and Cox regression models. RESULTS: Most patients had a pancreatic (40%) or small bowel (25%) neuroendocrine tumor (NET) primary. The majority of patients (60%) had bilateral liver disease. At surgery, 78% of patients underwent hepatic resection, 3% ablation alone, and 19% resection + ablation. Major hepatectomy was performed in 45% of patients, and 14% underwent a second liver operation. Carcinoid was the most common NET histological subtype (53%). Median survival was 125 months, with overall 5- and 10-year survival of 74%, and 51%, respectively. Disease recurred in 94% of patients at 5 years. Patients with hormonally functional NET who had R0/R1 resection benefited the most from surgery (P = 0.01). On multivariate analyses, synchronous disease [hazard ratio (HR) = 1.9], nonfunctional NET hormonal status (HR = 2.0), and extrahepatic disease (HR = 3.0) remained predictive of worse survival (all P < 0.05). CONCLUSIONS: Liver-directed surgery for NELM is associated with prolonged survival; however, the majority of patients will develop recurrent disease. Patients with hormonally functional hepatic metastasis without prior extrahepatic or synchronous disease derive the greatest survival benefit from surgical management.