Introduction
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with survival rates rarely exceeding 10% at 5 years despite advances in surgery and systemic therapy. While tumour biology and stage are well-established prognostic factors, the role of tumour location—head versus body/tail—has remained controversial, with prior studies yielding inconsistent results.
Problem Statement
Existing evidence on the prognostic impact of tumour location in PDAC is limited by heterogeneity in study design, small sample sizes, and inadequate adjustment for confounding variables. This uncertainty creates difficulty in clinical decision-making, particularly regarding surgical risk stratification, perioperative planning, and patient counselling.
Summary
This large multi-institutional TriNetX analysis provides robust evidence that tumor location significantly influences outcomes after resection. Tumors located in the pancreatic head are associated with higher perioperative mortality, increased risk of sepsis, and worse long-term survival compared to body/tail tumors. Even after propensity matching, head tumors demonstrated shorter median survival and higher overall mortality, confirming tumor location as an independent prognostic factor. These findings highlight the need for location-specific surgical strategies, risk assessment, and postoperative management to improve outcomes in PDAC.