Revisiting chronic pancreatitis as a risk factor for pancreatic ductal adenocarcinoma: toward precision risk...

Chronic pancreatitis (CP) is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). However, individual risk varies substantially, and the association between CP and PDAC is more complex than a uniform inflammation-driven pathway. Reverse causation, shared etiological factors, and biological heterogeneity may contribute to the observed association.

We critically review epidemiological, mechanistic, and causal evidence linking CP with PDAC, focusing on heterogeneity across CP subtypes and disease trajectories. We examine five domains potentially relevant to individual PDAC risk: genetic susceptibility, cumulative pancreatic injury, metabolic trajectories including new-onset diabetes, longitudinal imaging phenotypes, and emerging molecular alterations. We propose a multidomain framework for individualized and dynamic risk stratification and risk-adapted surveillance.

CP should not be regarded as a uniformly high-risk condition for PDAC. Individual risk is shaped by the interaction of genetic, inflammatory, metabolic, structural, and molecular factors. The key question should therefore shift from whether CP increases PDAC risk to which patients are most likely to develop clinically consequential PDAC. Although multidomain and longitudinal assessment may enable targeted surveillance, most biomarkers and prediction strategies remain insufficiently validated. Prospective studies are required to determine whether this approach improves early detection and patient outcomes.