Impact of the Extent of Resection of Neuroendocrine Liver Metastases on Survival: A Systematic Review and Meta-Analysis

Background: In patients with neuroendocrine tumors (NETs) with liver metastases(NELMs), complete resection of both the primary and liver metastases is a potentially curative option. However, where complete resection is not possible, debulking of the tumour burden has been proposed to prolong survival. The objective of current systematic review was to evaluate the effect of curative (R0-R1) and debulking surgery (R2) on overall survival (OS) in NELMs. For the subgroup of R2 resections, outcomes were compared by the degree of hepatic debulking (≥90%or≥70%). Methods: A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines using PubMed, Medline, CINAHL, Cochrane and Embase databases. Hazard ratios (HRs) were estimated for each study, and pooled using a random-effects inverse-variance meta-analysis model. Results: Of the 538 articles retrieved, 11 studies (1729 patients) reported comparisons between curative and debulking surgery; pooling these studies found OS to be significantly shorter in debulking resections, with an HR:3.49 (95% CI:2.70–4.51,p<0.001). Five studies (654 patients) compared outcomes between ≥90% and ≥70% hepatic debulking approaches. Whilst these studies reported a tendency for OS, as well as progression-free survival, to be shorter in those with a lower degree of debulking, they did not report sufficient data for this to be assessed on formal meta-analysis. Conclusion: In patients with NELM, OS following surgical resection is best achieved with R0-R1 resection. There is also evidence of a progressive reduction in the survival benefit with lesser debulking of tumour load.