In this thesis, we discusse the management of nonmetastatic, locally advanced unresectable or borderline resectable exocrine pancreatic cancer (BR-PDAC), specifically pancreatic ductal adenocarcinoma (PDAC). Disease Overview • Surgical resection is the only curative treatments for nonmetastatic exocrine pancreatic cancer. • Only 15-20% of patients present with resectable disease at diagnosis. • Approximately 40% have distant metastases, and 30-40% have locally advanced unresectable tumors. Pretreatment Considerations • A multidisciplinary approach is important for optimal patient care. • Tissue diagnosis is crucial before starting neoadjuvant therapy. • Biliary decompression may be necessary for patients undergoing neoadjuvant therapy. Management of Locally Advanced, Unresectable Disease • Initial systemic chemotherapy is preferred over radiation therapy or chemoradiotherapy. • Treatment is tailored based on genetic testing results, particularly for homologous repair deficiency (HRD) gene variants. • Modified FOLFIRINOX or gemcitabine plus nab-paclitaxel are common treatment options. • Resectability is reassessed after 4-6 months of chemotherapy. Management of Borderline Resectable Disease • Neoadjuvant therapy followed by restaging and surgical exploration is preferred over upfront surgery. • Systemic combination chemotherapy is typically offered as neoadjuvant therapy. Adjuvant Therapy • Adjuvant systemic therapy is recommended to complete a total of six months of systemic chemotherapy. • Modified FOLFIRINOX is preferred for patients with excellent performance status. The approach emphasizes personalized treatment based on disease extent, patient factors, and genetic testing results, involving ongoing assessment of resectability throughout the treatment course.