A multi-institutional analysis on neuroendocrine liver metastasis from pancreatic neuroendocrine tumors

Abstract

Objective: Neuroendocrine tumors typically arise from pancreatic (PNET) vs. gastrointestinal or thoracic origins (non-PNET). The impact of primary tumor site on long-term prognosis following resection of neuroendocrine liver metastasis (NELM) remains poorly defined. The objective of the study was to define the association of primary tumor location on prognosis of patients undergoing hepatic resection for NELM. Methods: Between 1990 and -2014, 421patients who underwent resection of NELM were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified by location of the primary tumor (PNETvs non-PNET). A propensity score matched analysis was utilized to assess the impact of primary tumor location on long-term survival. Results: Overall, 197(46.8%) patients had NELM from a PNET primary while 224 (53.2% had a non-PNET primary (small bowel, n=145; rectal, n=10; bronchial, n=22; other, n=47). The extent of liver involvement was comparable among PNET vs. non-PNET patients (>50%: 70.6% vs. 76.3%, respectively; P=0.19). Patients with PNET and NELM were, however, more likely to have extrahepatic disease (5.6%) compared with non-PNET patients (12.9%) (P=0.01). At the time of surgery, most patients underwent a minor resection (<3 segments) (PNET, 63.8% vs. non-PNET, 60.3%; P=0.46). On final pathology, patients with a primary PNET were more likely to have NELM characterized as moderate- or poorly-differentiated (P=0.005). Post-operatively, patients with a history of primary PNET were less likely to receive somatostatin-analog/targeted adjuvant therapy than non-PNET patients (15.2% vs. 29.9%, respectively; P<0.001). Patients with PNET+NELM had a worse disease-free (DFS) and overall survival (OS) compared with patients who had non-PNET+NELM (DFS: PNET, 36.2% vs. non-PNET55.2%; OS: PNET, 69.5% vs. non-PNET 83.4%; both P<0.01). However, after propensity score matching, while the presence of extrahepatic disease and tumor grade were associated with DFS (extrahepatic disease: HR 2.12; 95% CI, 1.19–3.75; P=0.010; tumor grade: HR 1.91; 95% CI, 1.43–2.55; p<0.001)and OS (extrahepatic disease: HR 3.09; 95% CI, 1.65–5.79; P<0.001; tumor grade: HR 1.76; 95% CI, 1.25–2.48; P=0.001), primary tumor location was not associate with long-term outcomes (DFS: HR 0.92, 95% CI, 0.60–1.42; OS: HR 0.93. 95% CI, 0.58–1.49; both P>0.05). Conclusion: PNET patients present with NELM with extra-hepatic disease and worse tumor grade. On propensity matched analysis factors such as extra-hepatic disease and tumor grade, but not primary tumor location, were associated with prognosis.