Initial Site of Metastasis Influences Prognosis in Pancreatic Ductal Adenocarcinoma

Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a highly aggressive malignancy. Prior studies suggest that the initial site of metastasis may impact prognosis. This study investigates whether overall survival in mPDAC patients differs between patients first presenting with lung metastases versus those presenting with liver metastases.

This retrospective analysis utilized the multi-institutional TriNetX database, identifying patients with histologically diagnosed PDAC who initially presented with either liver or lung metastases. Demographic, histologic, and outcome data were collected and analyzed. Patients were matched 1:1 using a nearest neighbor propensity score (PS) algorithm, and Kaplan-Meier survival analyses were performed. Cox regression was also used to further validate the results of the PS matching.

A total of 6256 patients were identified, including 5390 patients presenting with liver and 866 patients presenting with lung metastases at diagnosis. The mean age was 66.6 ± 10.5, the male-to-female ratio was 54%:46%, the mean carbohydrate-antigen (CA) 19-9 level was 1309 ± 2078 ng/mL, the mean carcinoembryonic-antigen (CEA) level was 117 ± 1044 U/mL. Propensity score matching yielded 848 matched pairs. Median survival from time of metastatic diagnosis was significantly longer for patients with lung metastases compared to liver (377 vs. 195 days, p < 0.0001). Cox regression identified several factors associated with increased risk of death: older age, obesity, malnutrition, and elevated CEA or CA 19-9. Additionally, initial lung metastases were associated with decreased risk of death (HR = 0.61, p < 0.0001).

Initial presentation with lung metastases appears to be associated with improved survival outcomes as compared to initial presentation with liver metastases in patients with mPDAC.