Neoadjuvant therapy is associated with a reduced lymph node ratio in patients with potentially resectable pancreatic cancer

Abstract

Background: The use of neoadjuvant therapy (NAC) for the treatment of potentially resectable pancreatic cancer remains controversial. In this study, we sought to evaluate cancer-specific endpoints in patients undergoing a NAC versus a surgery-first (SF) approach with specific emphasis on lymph node metastases.

Methods: A total of 222 patients who underwent NAC and 85 patients who underwent SF were identified from 1990 to 2008 and compared for cancer-related endpoints. Peripancreatic lymph nodes from 135 neoadjuvant therapy patients were evaluated for histologic tumor regression.

Results: Patients who underwent NAC followed by surgery had improved overall survival and time to local recurrence compared with the SF approach. NAC patients were less likely to have lymph node metastases (p = 0.001), lymphovascular invasion (LVI), and had smaller tumors. On multivariate analysis, lymph node positivity was associated with SF, tumor size, and the presence of LVI. NAC patients with N0 disease had equivalent outcomes to patients with a low-LNR (0.01-0.15), whereas patients with a LNR >0.15 had reduced survival, and time to local and distant recurrence. Ten of 135 (7.4 %) NAC patients had evidence of tumor regression in at least one lymph node.

Conclusions: Patients with potentially resectable PDAC selected to undergo NAC had improved survival and longer time to recurrence. Although some of these differences may be related to improvements in multimodality therapy completion rates, tumor regression in lymph node metastases exists and may demonstrate a biologic benefit of NAC compared with a SF approach.

Figures

Figure 1

Kaplan-Meier estimate of (A) overall survival for all patients who underwent neoadjuvant therapy (NAC, all), NAC +/− resection vs. surgery first. (B, C) Kaplan-Meier estimate of time to local recurrence (B) and time to distant recurrence (C) for patients who underwent neoadjuvant therapy and resection (NAC, resected) vs. surgery first. (D) 2 & 5-year overall Survival, local and distant recurrence rates for patients who underwent NAC + resection vs. surgery first.

Figure 2

Kaplan-Meier estimate of (A) overall survival (B) time to local recurrence and (C) time to distant recurrence for patients who underwent neoadjuvant chemoradiation stratified by LNR.

Figure 3

Hematoxylin & Eosin 40x section of lymph nodes. (A) Untreated: negative for metastasis; (B) Untreated: positive for metastasis; (C) Neoadjuvant CXRT: negative for metastasis; (D) Neoadjuvant CXRT: geographic area of fibrosis within lymph node, suggestive of treatment effect on a metastatic deposit.