Tumor necrosis of primary malignancy affects survival and outcome in patients with liver metastases from neuroendocrine tumors

Question. Reliable biomarkers represent a crucial unmet need in the management of neuroendocrine tumors. Histologic tumor necrosis has been suggested to have a prognostic value in selected solid tumors but is not included in established WHO NET Grading Systems. However, little is known regarding the influence of tumor necrosis on tumor progression and prognosis in patients with liver metastasis from neuroendocrine tumors.

Methods. We analyzed retrospectively all patients (n = 55) with liver metastasis form neuroendocrine tumors of pancreas and gastro-intestinal tract, who underwent surgery between January 2014 and September 2017, for formation of histologic tumor necrosis in primary cancer and hepatic metastases. Necrosis score was correlated with clinicopathologic characteristics, tumor recurrence and patients” survival. Statistical analysis was performed using SPSS software.

Results. Formation of tumor necrosis was associated with Ki67 proliferation index (ρ < 0.05) and showed a strong tendency to enhanced tumor recurrence and peritoneal carcinosis, fibrosis, higher grading, perineural sheet infiltration, and tumor synaptophysin expression. Furthermore, patients with occurrence of histologic tumor necrosis revealed reduced overall survival (ρ < 0.05). Tumor necrosis along with other established prognostic variables for NET, was confirmed as independent prognostic factor for survival in the multivariate analysis (all ρ < 0.05).

Conclusions. Overall survival of patients with NET liver metastasis significantly deteriorated in presence of histologic necrosis, when compared to patients with absence of tumor necrosis. These observations suggest the utilization of necrosis score, in addition to other established prognosticators, as valuable prognostic marker in NET, and might indicate more individualized management of these patients.