Adjuvant Therapy in Pancreatic Ductal Adenocarcinoma—Past, Present, and Future

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies despite advances in surgical techniques and systemic therapy. Although surgical resection offers the only potential for cure, recurrence is common, underscoring the critical role of multimodal treatment. Over the past two decades, numerous clinical trials have cemented adjuvant chemotherapy as a cornerstone of multimodal management in resected PDAC, with progressive evolution from single-agent regimens to modern multiagent regimens. In contrast, the role of chemoradiation remains debated, with the body of evidence demonstrating conflicting results. Ongoing clinical trials are expected to elucidate optimal treatment modalities. Emerging targeted therapies, biomarker-directed treatment approaches, and immunotherapeutic strategies also hold promise for improving outcomes in select patient populations. This narrative review summarizes the landmark trials that have shaped adjuvant therapy, examines the evolution of adjuvant treatment over time, reviews current management guidelines, and highlights promising emerging therapeutic directions likely to influence the management of localized pancreatic cancer.