Para-aortic lymph node involvement should not be a contraindication to resection of pancreatic ductal adenocarcinoma

ARTICLE HIGHLIGHTS

Research background

Pancreatic ductal adenocarcinoma (PDAC) presents as localised disease for only a small subset of patients for whom only 20% are eligible for resection with 5-year survival of 6.8%. Nodal status is amongst the most important prognostic indicators. Para-aortic lymph nodes found in the aortocaval groove (PALN) are staged as distant metastatic (M1) disease and are found in 14%-18% of pancreatic head/uncinate PDAC at resection. Various studies have alluded to PALN metastases being associated with poor prognosis, whereas others have failed to replicate this effect and a meta-analysis has only concluded the need for intra-operative assessment of PALN. A consensus statement from the International Study Group for Pancreatic Surgery supported standard lymphadenectomy for pancreatic resections, which does not include PALN.

Research motivation

Currently, whether intra-operative assessment of PALN should be undertaken or whether there is sufficient evidence that resection should be abandoned depends on surgeon or unit policy.

Research objectives

The aim of this study was to determine the prognostic significance of PALN metastases on the oncological outcomes after pancreatic resections for PDAC.

Research methods

This is a retrospective cohort study of data from a prospectively maintained database on consecutive patients undergoing pancreatectomies for PDAC where PALN was sampled between 2011 and 2020 in a tertiary specialist centre. The study was conducted in line with STROBE (Strengthening the Reporting of Observational studies in Epidemiology) guidelines. Staging of the tumours was based on the NCCN staging criteria. PALN were sampled from the infra-renal, aortacaval lymph nodes and more specifically from the level of the third part of the duodenum to the angle of the left renal vein (station 16). PALN sampling was performed at the discretion of the operating surgeon. Over the last 3 years of the study 3 surgeons sampled PALN routinely, accounting for 36% of the cases in the study. Follow-up of patients was determined from time of diagnosis until disease recurrence or death. OS was defined as the time from diagnosis to death or last follow-up and disease free survival as the time from resection to diagnosis of disease recurrence.

The cohort characteristics are presented with standard descriptive statistical analysis. One way Anova, Chi-Square and Mann-Whitney U tests were used as appropriate for statistical comparisons with statistical significance set at P < 0.05. Exact statistics were used for all tests to account for small sample size. Survival analysis was performed with the Kaplan-Meier method and log rank test was used to compare survival curves. Univariable and multivariable time to event analyses were performed using the Cox proportional hazard model to determine risk factors for median OS and disease-free survival (DFS). Variables were subjected to a univariable analysis first and those with P < 0.2 were introduced into a multivariable model. Hazard ratios and associated 95% confidence intervals were calculated. A two-tailed P value < 0.05 was considered statistically significant. All statistical analyses were performed using the software package SPSS Statistics for Windows (version 25.0; SPSS Inc., Chicago, IL, United States).

Research results

81 cases had PALN sampling and 17 (21%) were positive. Pathological N stage was significantly different between PALN+ and PALN- patients (P = 0.005), while no difference was observed in any of the other characteristics. Preoperative imaging diagnosed PALN positivity in one case. OS and DFS were comparable between PALN+ and PALN- patients with lymph node positive disease (OS: 13.2 mo vs 18.8 mo, P = 0.161; DFS: 13 mo vs 16.4 mo, P = 0.179). No difference in OS or DFS was identified between PALN positive and negative patients when they received chemotherapy either in the neoadjuvant or in the adjuvant setting (OS: 23.4 mo vs 20.6 mo, P = 0.192; DFS: 23.9 mo vs 20.5 mo, P = 0.718). On the contrary, when patients did not receive chemotherapy, PALN disease had substantially shorter OS (5.5 mo vs 14.2 mo; P = 0.015) and DFS (4.4 mo vs 9.8 mo; P < 0.001). PALN involvement was not identified as an independent predictor for OS after multivariable analysis, while it was for DFS doubling the risk of recurrence.

Research conclusions

This study suggests that PALN sampling is safe and should be routinely performed during resection of PDAC for accurate staging, even in the absence of involvement in the pre-operative imaging. PALN involvement does not affect OS when patients complete the indicated treatment pathway (surgery and chemotherapy) and occult involvement identified intra-operatively should not be considered as a contraindication to resection.

Research perspectives

Future studies should focus on improving pre-operative diagnosis and on the value of NAT for these cases.