Extrapancreatic extension exhibits tumor size-dependent prognostic impact in pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy requiring precise prognostic stratification. Although extrapancreatic extension (EPE) was removed from the American Joint Committee on Cancer 8th edition staging system in favor of size-based classification, emerging evidence suggests EPE retains prognostic relevance. This population-based study analyzed 22,045 patients with surgically resected PDAC from the Surveillance, Epidemiology, and End Results database (2004–2022) to evaluate EPE’s prognostic significance and its interaction with tumor size. EPE was present in 78.0% of patients and independently predicted worse disease-specific survival (adjusted hazard ratio, 1.29; 95% confidence interval, 1.23–1.35). Notably, the prognostic impact of EPE varied nonlinearly with tumor size, exerting a stronger effect on smaller tumors. A modest but significant negative multiplicative interaction was identified (adjusted hazard ratio, 0.88; 95% confidence interval, 0.79–0.98), suggesting that patients with small EPE-positive tumors exhibited survival comparable to those with larger EPE-negative tumors. These findings were consistent across competing risk analyses. This study demonstrates that EPE remains an important prognostic factor in PDAC, with its effect modulated by tumor size. These results suggest that EPE assessment may warrant consideration in future postoperative staging and risk-stratification frameworks.