Ann Hepatobiliary Pancreat Surg.  2022 Feb;26(1):31-39. 10.14701/ahbps.21-101.

Impact of the extent of resection of neuroendocrine tumor liver metastases on survival: A systematic review and meta-analysis

• Kulkarni R
• Kabir I
• Hodson J
• Raza S
• Shah T
• Pandanaboyana S
• Dasari BVM

• KMID: 2526830
• DOI: http://doi.org/10.14701/ahbps.21-101

Abstract

In patients with neuroendocrine tumors with liver metastases (NETLMs), complete resection of both the primary and liver metastases is a potentially curative option. When complete resection is not possible, debulking of the tumour burden has been proposed to prolong survival. The objective of this systematic review was to evaluate the effect of curative surgery (R0-R1) and debulking surgery (R2) on overall survival (OS) in NETLMs. For the subgroup of R2 resections, outcomes were compared by the degree of hepatic debulking (≥ 90% or ≥ 70%). 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. Of 538 articles retrieved, 11 studies (1,729 patients) reported comparisons between curative and debulking surgeries. After pooling these studies, OS was found to be significantly shorter in debulking resections, with an HR of 3.49 (95% confidence interval, 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 and 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 in a formal meta-analysis. In patients with NETLM, OS following surgical resection is the best to achieve R0-R1 resection. There is also evidence for a progressive reduction in survival benefit with lesser debulking of tumour load.

Keyword

Neuroendocrine tumors; Liver metastasis; Debulking surgery; Survival

Figure

• 

  Fig. 1 PRISMA flowsheet showing selection of studies.

• 

  Fig. 2 Forest plot of overall survival by cytoreductive strategy. Elias et al. [12], Nave et al. [25], and Wängberg et al. [21] treated R0 rather than R0-R1 as the reference category, whilst Woltering et al. [15] compared 70%–89% and < 90% debulking for small bowel and pancreatic neuroendocrine tumors, respectively. The lower confidence interval reported by Elias et al. [12] was truncated to improve scaling. a)Studies indicated by squares defined groups using liver-specific rather than overall R-status—excluding these studies returned a similar pooled hazard ratio of 3.28 (95% confidence interval, 2.26–4.77; p < 0.001; I2 = 0%).

• 

  Fig. 3 Funnel plot of overall survival by cytoreductive strategy. Studies included in the plot and pooled hazard ratio used to generate the funnel are the same as for Fig. 2. SE, standard error; ln, natural logarithm.

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