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
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 resection of the primary tumour and regional lymphadenectomy results in a high cure rate for patients with GEP NETs.
LN positivity and LN ratio (LNR) are independent prognostic factors for survival in patients with resected NETs, but limited evidence is available on the optimal predictive number of resected LNs required. Several retrospective studies in Pancreatic NETs (PanNETs) and Small Bowel NETs (SiNETs) have emphasized the importance of adequate resection of regional LNs in patients undergoing curative resection. The current guidelines (AJCC TNM staging 8th edition and ENETS) for the management of GEPNETs do not provide a recommendation regarding LN yield. The main purpose of the study was to identify a cut off value for LN retrieval in resected GEP NETs.
This retrospective study was conducted to identify the optimal number of LNs that should be harvested in patients with GEP NETS undergoing curative surgery and to evaluate the association between LN metastases and survival (relapse-free and overall) in patients with resected well differentiated GEP NETs.
Data on patients who underwent curative surgery for GEP NETs between January 2002 and March 2017 were identified and analysed retrospectively. Univariate Cox proportional hazard (CPH) 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. LN cut-point value was determined using the cut-point determination methods in survival analysis, using R. This is an outcome-oriented method providing a value of a cut-point that corresponds to the most significant relationship with survival.
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 (median 1.8) on RFS: P = 0.1 or OS: P = 0.75. LN cut-point value associated with RFS was 8. Tumour necrosis (P = 0.021) and perineural invasion (P = 0.016) were the only two variables significantly associated with worse OS. Retrieval of ≥ 8 LNs (HR = 2.70, 95%CI: 1.07-6.84, P = 0.036), tumour localisation: pancreas (HR = 27.33, P = 0.006) and small bowel (HR = 32.44, P = 0.005) were independent prognostic factors for shorter RFS on multivariable analysis.
The study has concluded that 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. A prospective multicentre study is warranted with a clear direction on recommended surgical practice and follow-up guidance for GEP NETs.