Total neoadjuvant treatment for pancreatic adenocarcinoma is associated with limited lymph node yield but improved ratio

Abstract

Presenter: Maitham Moslim MD | Fox Chase Cancer Center Background: The lymph node yield (LNY) and lymph node ratio (LNR) of nodal metastases to total harvested lymph nodes after pancreatoduodenectomy (PD) have been reported as essential parameters for the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). We present the first study comparing LNY and LNR in the setting of different neoadjuvant therapy approaches for PDAC. Understanding the influence of neoadjuvant therapy on LNY may help reassess the minimal requirement of 12 harvested lymph nodes to achieve adequate oncologic staging in PDAC. Methods: 134 patients diagnosed with resectable, borderline-resectable and locally-advanced PDAC who underwent PD between 2010-2019 were identified. Pathology reports were examined to obtain LNY and calculate LNR. Patients were categorized based on first-line treatment as: surgery first (SF), total neoadjuvant therapy (TNT) and non-TNT neoadjuvant therapy (NTNT). Patients who received TNT were stratified in three groups: incomplete TNT, induction TNT (chemotherapy prior to chemoradiotherapy) and consolidation TNT (chemoradiotherapy prior to chemotherapy). Results: 49 patients (36.6%), 38 (28.4%), 12 (9%), 27 (20%) and 8 (6%) underwent SF approach, NTNT, induction TNT, incomplete TNT and consolidation TNT, respectively. Patients who underwent the SF approach were older than the induction TNT group (median: 71 vs. 62 years, respectively; p = 0.0068). There were no statistically significant differences between groups comparing gender and index cancer antigen 19-9 (CA 19-9) levels (p = 0.95 and 0.62, respectively). Preoperative evaluation of sectional imaging declared 8.2% of tumors borderline resectable in the SF group, while this percentage was significantly higher in the NTNT, induction TNT, incomplete TNT and consolidation TNT groups (63,2%, 70.2%, 75% and 75%, respectively; p = < 0.0001). There was no difference in R0 resection and vascular resection between the groups (p = 0.09 and 0.79, respectively). The median counts of LNY on final pathology were 22, 15, 21, 11.5 and 10 for the SF approach, NTNT, incomplete TNT, induction TNT and consolidation TNT, respectively (p<0.0001). The median LNR was 0.16, 0.07, 0.03, 0.02 and 0.02, respectively (p = 0.0002). No significant differences in postoperative CA19-9 levels or recurrence rates between the groups were noted (p = 0.24 and p = 0.81). There was no difference in overall survival (OS) or disease-free survival (DFS) between the treatment groups. Conclusion: PDAC patients who undergo TNT prior to PD exhibits lower LNY and improved LNR compared to the SF approach and non-TNT neoadjuvant therapy groups, although no significant differences were demonstrated in DFS or OS. This is likely explained by the increased treatment response and lymph node obliteration associated with the TNT approach. Our study questions the minimal requirement of 12 harvested lymph nodes in patients who undergo PD for PDAC following TNT.