Clinical Implications of Extensive Lymph Node Metastases for Resected Pancreatic Cancer

Outcomes of patients with resected pancreatic ductal adenocarcinoma (PDA) and extensive lymph node metastases have not been fully characterized.

A total of 637 patients underwent resection for pancreatic ductal adenocarcinoma (PDA) between 2002 and 2014 at the Thomas Jefferson University. Positive lymph node count (LNC) and positive lymph node ratio (LNR) were analyzed as predictors of cancer-specific outcomes, with a focus on outcomes of patients with extensive lymph node burden.

Resected patients with regional lymph node metastases had a median survival of 17.1 months (n = 425, 70%) compared with 25.5 months (n = 185, 30%) for patients without lymph node spread (N0) (hazard ratio [HR] = 1.9, p < 0.001). Overall survival decremented with increased lymph node spread, but plateaued for LNC ≥ 4 (HR 2.4 vs. N0, p < 0.001) and LNR ≥ 0.4 (HR 2.2, p < 0.001). Compared with historical cohorts with macroscopic metastatic disease, as opposed to microscopic, superior long-term survival was achieved in patients with extensive lymph node metastases (LNC ≥ 4); 24- and 36-month survivals were 25% (vs. 16%, p < 0.001) and 12% (vs. 6%, p < 0.001), respectively. Extensive lymph node burden was associated with increased baseline postoperative serum CA 19-9 (p = 0.044) and systemic recurrence (p < 0.001).

The prognostic impact of extensive lymph node spread after resection for PDA plateaus above a specific threshold (LNC ≥ 4 or LNR ≥ 0.4), supporting the new 8th edition AJCC criteria for N2 disease. Clinically, lymph node spread above this threshold seems to correlate with occult systemic disease (elevated postoperative CA 19-9 and systemic pattern of failure).