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

BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Its larger mass 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. Thus, this study aims to quantitatively identify the objective relationship between tumor size and prevalence of LN metastases across primary tumor size spectrums. METHODS 9,958 resected PDAC patients without distant metastasis were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The prevalence of LN metastases, LN ratio (LNR) and N2/N1 ratio were assessed amongst different tumor sizes, and the relationships were depicted 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%, and then fluctuated between 70.0% and 80.0% when 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. CONCLUSION Regional LN involvement demonstrated a logarithmic growth with increasing tumor sizes in resectable PDAC patients. The probability of metastasis in each regional LN for resectable PDAC patients 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.