Published online Apr 24, 2020. doi: 10.5306/wjco.v11.i4.205
Peer-review started: December 24, 2019
First decision: February 20, 2020
Revised: February 29, 2020
Accepted: April 8, 2020
Article in press: April 8, 2020
Published online: April 24, 2020
Processing time: 119 Days and 17 Hours
The prognostic significance of lymph nodes (LNs) metastases and the optimum number of LN yield in gastroenteropancreatic neuroendocrine tumours (GEP NETs) undergoing curative resection is still debatable. Many studies have demonstrated that cure rate for patients with GEP NETs can be improved by the resection of the primary tumour and regional lymphadenectomy
To evaluate the effect of lymph node (LN) status and yield on relapse-free survival (RFS) and overall survival (OS) in patients with resected GEP NETs.
Data on patients who underwent curative resection for GEP NETs between January 2002 and March 2017 were analysed retrospectively. Grade 3 tumours (Ki67 > 20%) were excluded. Univariate Cox proportional hazard models were computed for RFS and OS and assessed alongside cut-point analysis to distinguish a suitable binary categorisation of total LNs retrieved associated with RFS.
A total of 217 patients were included in the study. The median age was 59 years (21-97 years) and 51% (n = 111) were male. Primary tumour sites were small bowel (42%), pancreas (25%), appendix (18%), rectum (7%), colon (3%), gastric (2%), others (2%). Median follow up times for all patients were 41 mo (95%CI: 36-51) and 71 mo (95%CI: 63–76) for RFS and OS respectively; 50 relapses and 35 deaths were reported. LNs were retrieved in 151 patients. Eight or more LNs were harvested in 106 patients and LN positivity reported in 114 patients. Three or more positive LNs were detected in 62 cases. The result of univariate analysis suggested perineural invasion (P = 0.0023), LN positivity (P = 0.033), LN retrieval of ≥ 8 (P = 0.047) and localisation (P = 0.0049) have a statistically significant association with shorter RFS, but there was no effect of LN ratio on RFS: P = 0.1 or OS: P = 0.75. Tumour necrosis (P = 0.021) and perineural invasion (P = 0.016) were the only two variables significantly associated with worse OS. In the final multivariable analysis, localisation (pancreas HR = 27.33, P = 0.006, small bowel HR = 32.44, P = 0.005), and retrieval of ≥ 8 LNs (HR = 2.7, P = 0.036) were independent prognostic factors for worse RFS.
An outcome-oriented approach to cut-point analysis can suggest a minimum number of adequate LNs to be harvested in patients with GEP NETs undergoing curative surgery. Removal of ≥ 8 LNs is associated with increased risk of relapse, which could be due to high rates of LN positivity at the time of surgery. Given that localisation had a significant association with RFS, a prospective multicentre study is warranted with a clear direction on recommended surgical practice and follow-up guidance for GEP NETs.
Core tip: There is no consensus on the optimal number of lymph node (LN) retrieval in patients undergoing resection for gastroenteropancreatic neuroendocrine tumours (GEP NETs). The purpose of this study was to evaluate the LN status and yield on relapse-free survival and overall survival in patients with resected GEP NETs. By using the outcome-oriented approach to cut-point analysis, this study suggested a retrieval of a minimum of eight or more LNs in patients with GEP NETs undergoing curative surgery. The risk of relapse was high in patients who had ≥ 8 LNs retrieved and a high LN yield and LN positivity were seen in small intestinal NETs and pancreatic NETs. The localisation has a significant association with relapse-free survival, necessitating stricter surveillance especially for intestinal NETs and pancreatic NETs.