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

Joseph R Habib; Ingmar F Rompen; Ammar A Javed; Mahip Grewal; Benedict Kinny-Köster; Paul C M Andel; D Brock Hewitt; Greg D Sacks; Marc G Besselink; Hjalmar C van Santvoort; Lois A Daamen; Martin Loos; Jin He; Markus W Büchler; Christopher L Wolfgang; I Quintus Molenaar

doi:10.1111/jgh.16686

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

J Gastroenterol Hepatol. 2024 Jul 31. doi: 10.1111/jgh.16686. Online ahead of print.

Authors

Joseph R Habib^{1

2}, Ingmar F Rompen^{1

3}, Ammar A Javed¹, Mahip Grewal¹, Benedict Kinny-Köster³, Paul C M Andel², D Brock Hewitt¹, Greg D Sacks¹, Marc G Besselink^{4

5}, Hjalmar C van Santvoort², Lois A Daamen^{2

6}, Martin Loos³, Jin He⁷, Markus W Büchler⁸, Christopher L Wolfgang¹, I Quintus Molenaar²

Affiliations

¹ Department of Surgery, New York University Langone Health, New York, New York, USA.
² Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands.
³ Heidelberg University Hospital, Heidelberg, Germany.
⁴ Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands.
⁵ Cancer Center Amsterdam, Amsterdam, The Netherlands.
⁶ Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
⁷ Department of Surgery, Johns Hopkins Hospital, Baltimore, Maryland, USA.
⁸ Champalimaud Foundation, Lisbon, Portugal.

PMID: 39086101
DOI: 10.1111/jgh.16686

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.

Keywords: colloid; intraductal papillary mucinous neoplasm; invasive IPMN; pancreatic cancer; pancreatic cyst; pancreatic neoplasms; tubular.