DISSECTING THE ROLE OF NODAL METASTASES LOCATION IN PANCREATODUODENECTOMY AFTER NEOADJUVANT TREATMENT FOR CANCER: RESULTS FROM A PROSPECTIVE LYMPHADENECTOMY PROTOCOL

Introduction
The role of lymph node (LN) parameters in pancreatoduodenectomy (PD) for cancer has been mainly investigated in the upfront surgery setting. Yet, due to the impact of neoadjuvant therapy (NAT) on nodal status, these results cannot be directly translated to post-NAT PD. This study aimed to examine LN yields and metastases per anatomical stations and how the extension of LN dissection affects nodal staging in post-NAT PD. Lastly, the prognostic role of LN parameters was investigated.
Methods
An institutional lymphadenectomy protocol was prospectively applied to all post-NAT PDs from June 2013. Lymphadenectomy included stations 5/6/8a-p/12a-b-c-p/13/14a-b/17 and jejunal mesentery LNs. Stations embedded in the PD specimen (13/14/17/jejunal) were defined as first-echelon, those sampled separately (5/6/8/12) as second-echelon. The prognostic impact of LN parameters in N+ patients was evaluated using uni- and multivariable Cox regression. To avoid collinearity, separate multivariable models were designed for each nodal parameter.
Results
Among 288 patients 61% received FOLFIRINOX, 30% Gem-Abraxane. The median number of examined (ELN) and positive LNs (PLN) were 43 and 1, and 185 patients were N+ (64%). The commonest metastatic sites were stations 13 (51%), 14 (34%) and 17 (32%). The overall rates of first and second echelon involvement were 60% and 20%. The median number of ELN and PLN in the first echelon were 29 and 1. The addition of second echelon LNs increased nodal counts by 9 ELN and 0 PLN, resulting in only minor changes in staging.
The median follow-up was 25.1 months, 35.8 in censored cases. At multivariable analysis, second echelon involvement, ≥4 metastatic stations, metastases to station 8 and jejunal mesentery LNs, but not N2 status, were independently associated with survival of N+ patients, along with adjuvant treatment.
The median recurrence-free survival (RFS) was 14.8 months and 176 patients experienced recurrence (71%), among which 41 were local relapses (23%). In N+ patients, nodal echelons, ≥4 metastatic stations and tumor involvement of station 8,14 and jejunal mesentery LNs were independent predictors of RFS, along with Ca 19.9 response, T- and R-status and adjuvant treatment. Distant recurrences incrementally increased with nodal involvement (Figure).
Conclusion
LN metastases most commonly occur in first-echelon LNs, and first-echelon dissection provides an adequate number of ELN for optimal staging. Examining second-echelon LNs does not improve the staging process substantially. Yet, second-echelon involvement is prognostically relevant, as well as metastases to station 8 and jejunal mesentery LNs. These data have potential implications when assessing surgical indication after NAT. Moreover, intraoperative frozen section of station 8 might help decision-making, especially in technically demanding cases or fragile patients.