Clinicopathological features and prognostic outcomes in pancreatic ductal adenocarcinoma with elevated alpha fetoprotein: a single-center retrospective study

Alpha-fetoprotein (AFP) elevation is uncommon in pancreatic ductal adenocarcinoma (PDAC), and its clinicopathological and prognostic significance remains unclear. We retrospectively characterized AFP-elevated PDAC and evaluated its prognostic significance. Patients with pathologically confirmed PDAC treated at our institution over a 10-year period were retrospectively reviewed. Patients with elevated serum AFP at admission were identified, and an institutional cohort of patients with AFP-normal PDAC was included for comparison. Clinicopathological characteristics, treatment patterns, and survival outcomes were evaluated. Restricted cubic spline (RCS) analysis explored the nonlinear association between continuous AFP levels and overall survival (OS) among patients with AFP-elevated PDAC. A total of 50 patients with AFP-elevated PDAC and 93 patients with AFP-normal PDAC were identified. In the cohort with elevated AFP, the median AFP level was 9.0 (7.6, 14.3) ng/ml, and the majority of patients were staged as T4 (16 cases, 37.2%), with staging predominantly at stage II or higher. No significant difference in OS was observed between the two groups. AFP elevation was not associated with OS in univariable analysis or after adjustment for TNM stage and resection status (HR, 1.23; 95% CI 0.73–2.06; P = 0.442). RCS analysis suggested a nonlinear association between AFP level and OS, with an estimated breakpoint of approximately 44 ng/ml. However, this finding was not consistently reproduced after sensitivity analyses addressing extreme AFP values or logarithmic transformation. AFP-elevated PDAC represents a rare clinical phenotype that frequently presents with advanced disease. In this cohort, AFP elevation was not significantly associated with OS after adjustment for disease stage and resection status. The potential nonlinear association between absolute AFP level and survival should be considered exploratory and requires validation in larger, multicenter cohorts.