Prevention Before Therapy in Pancreatic Ductal Adenocarcinoma: The Clinical, Economic, and Human Case for Weighting Resources Upstream

Abstract Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second-leading cause of US cancer death by 2030, and survival is dominated by stage at diagnosis: roughly 44% at five years for localized disease versus about 3% with distant metastases. Only about 15% of cases are detected while localized, surgery reaches a minority of patients, and no validated screening test exists for average-risk adults. This topical review examines the biologic, clinical, economic, psychological, equity, and therapeutic evidence bearing on where scarce resources should be directed. The long interval between initiating mutation and invasive disease provides a mechanistic rationale for prevention and interception, and the modifiable exposures of obesity, tobacco, type 2 diabetes, and alcohol act largely within that window. We consider innovations that extend prevention beyond lifestyle advice—incretin-based weight management, risk stratification anchored in new-onset diabetes and biomarkers, and immunoprevention—together with early-onset disease, implementation and policy, and the barriers and evidentiary limits that temper these arguments. We propose a three-tier framework of primary prevention, early detection in high-risk groups, and therapy, and argue that research, policy, and clinical investment should be weighted upstream, because every case prevented spares the cost, capacity, and suffering that the downstream tiers must otherwise absorb.