Outcomes in intraductal papillary mucinous neoplasm‐derived pancreatic cancer differ from PanIN‐derived pancreatic cancer

Abstract Background and Aim Intraductal papillary mucinous neoplasm (IPMN)‐derived pancreatic ductal adenocarcinoma (PDAC) management is generally extrapolated from pancreatic intraepithelial neoplasia (PanIN)‐derived PDAC guidelines. However, these are biologically divergent, and heterogeneity further exists between tubular and colloid subtypes. Methods Consecutive upfront surgery patients with PanIN‐derived and IPMN‐derived PDAC were retrospectively identified from international centers (2000–2019). One‐to‐one propensity score matching for clinicopathologic factors generated three cohorts: IPMN‐derived versus PanIN‐derived PDAC, tubular IPMN‐derived versus PanIN‐derived PDAC, and tubular versus colloid IPMN‐derived PDAC. Overall survival (OS) was compared using Kaplan–Meier and log‐rank tests. Multivariable Cox regression determined corresponding hazard ratios (HR) and 95% confidence intervals (95% CI). Results The median OS (mOS) in 2350 PanIN‐derived and 700 IPMN‐derived PDAC patients was 23.0 and 43.1 months ( P < 0.001), respectively. PanIN‐derived PDAC had worse T‐stage, CA19‐9, grade, and nodal status. Tubular subtype had worse T‐stage, CA19‐9, grade, nodal status, and R1 margins, with a mOS of 33.7 versus 94.1 months ( P < 0.001) in colloid. Matched ( n = 495), PanIN‐derived and IPMN‐derived PDAC had mOSs of 30.6 and 42.8 months ( P < 0.001), respectively. In matched ( n = 341) PanIN‐derived and tubular IPMN‐derived PDAC, mOS remained poorer (27.7 vs 37.4, P < 0.001). Matched tubular and colloid cancers ( n = 112) had similar OS ( P = 0.55). On multivariable Cox regression, PanIN‐derived PDAC was associated with worse OS than IPMN‐derived (HR: 1.66, 95% CI: 1.44–1.90) and tubular IPMN‐derived (HR: 1.53, 95% CI: 1.32–1.77) PDAC. Colloid and tubular subtype was not associated with OS ( P = 0.16). Conclusions PanIN‐derived PDAC has worse survival than IPMN‐derived PDAC supporting distinct outcomes. Although more indolent, colloid IPMN‐derived PDAC has similar survival to tubular after risk adjustment.