Clinical subtypes of stage IV pancreatic ductal adenocarcinoma: a new perspective of clinical practices

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies and becomes an increasing burden on our society, with nearly half of patients presenting with metastasis at diagnosis and a mortality rate that continues to rise during the past decade. Despite significant advances in understanding the molecular heterogeneity of PDAC, current classifications have yet to translate into clinical practice. In this review, we propose a novel clinical classification for stage IV PDAC based on distinct patterns of metastatic dissemination and highlight the ongoing efforts to tailor specific regimens for specific clinical subtypes. We further explore the underlying molecular mechanisms that may drive site-specific metastasis. We suggest that the new clinical subtypes could improve patient stratification, optimize clinical trial design, and ultimately enhance therapeutic outcomes in stage IV PDAC patients.