Early Metastatic Relapse in Resected Stage IB KRAS G12D Pancreatic Ductal Adenocarcinoma: Limitations of Anatomical Staging.

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor survival, although patients with localized resectable disease are generally expected to achieve improved outcomes following surgery and adjuvant chemotherapy. Increasing evidence, however, suggests that tumor biology may outweigh anatomical staging in determining prognosis. This case report describes the case of a 36-year-old male with low-risk factors diagnosed with stage IB pancreatic tail adenocarcinoma following evaluation for persistent dyspeptic symptoms. The patient underwent distal pancreatectomy with splenectomy and achieved a margin-negative, node-negative resection. Histopathology demonstrated lymphovascular and perineural invasion, while delayed molecular profiling identified a KRAS G12D mutation. Despite apparently favorable pathological staging and adjuvant FOLFIRINOX chemotherapy, the patient developed early biochemical progression with rapidly rising carbohydrate antigen 19-9 (CA 19-9) levels, followed by widespread metastatic dissemination involving the liver, lung, spine, skeletal muscle, and multiple visceral sites. Notably, disease progression occurred despite a transient biochemical response to second-line chemotherapy, highlighting discordance between tumor marker kinetics and true disease burden. The patient died 13 months after diagnosis. This case highlights the limitations of anatomical staging in PDAC and emphasizes the prognostic importance of tumor biology, including KRAS mutation status, lymphovascular invasion, and perineural invasion. It also demonstrates the potential limitations of CA 19-9 as a solitary marker of treatment response in biologically aggressive disease.