Lymph Node Metastatic Patterns and Survival Predictors Based on Tumor Size in Pancreatic Ductal Adenocarcinoma

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Larger tumor size is widely acknowledged to be associated with increased lymph node (LN) metastatic potential. However, the quantitative relationships between tumor size and LN metastasis or survival remain unclear. This study aims to quantify the objective relationship between tumor size and the prevalence of LN metastases across a spectrum primary tumor size.

Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 9958 patients with resected PDAC without distant metastasis. The prevalence of LN metastases, LN ratio (LNR), and N2/N1 ratio were assessed amongst different tumor sizes, and the relationships were displayed by matched curves.

Results: In the enrolled cohort, age, tumor site, grade, American Joint Committee on Cancer (AJCC) 8th node staging, tumor size, chemotherapy, and radiotherapy were identified as significant independent predictors for overall survival (OS) and cancer-specific survival (CSS). For tumors within 1-40 mm in size, the prevalence of node-positive disease is closely modelled using a logarithmic formula [0.249 × ln (size) + 0.452] × 100%. The prevalence plateaued between 70% and 80% beyond 40 mm. The mean LNR increased in a stepwise manner as tumor size increased from 1-5 mm (LNR = 0.024) to 41-45 mm (LNR = 0.177); then, beyond 45 mm, it plateaued near 0.170. N2/N1 ratio gradually increased along with tumor size from 1-5 mm (N2/N1 = 0.286) to 41-45 mm (N2/N1 = 1.016), and when tumor size reached to 41-45 mm or more, the ratio stabilized around 1.000. In addition, significant survival prediction by AJCC N staging was observed when tumors ranging between 16 and 45 mm in size.

Conclusion: Regional LN involvement demonstrated a logarithmic growth with increasing tumor sizes in patients with resected PDAC . The probability of metastasis in each regional LN for resected PDAC with tumors greater than 40 mm in size was near 17.0% and their overall prevalence of LN metastasis was 70-80%. Among which, 50% of patients had an N2 stage. Such prediction may be a potential and promising tool for guiding lymphadenectomy in PDAC surgery.

Keywords: Lymph node; Matched curve; Pancreatic ductal adenocarcinoma; Pancreatic neoplasms; Survival; Tumor size.