Impact of Adjuvant Chemotherapy on Resected Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Cancer: Results From an International Multicenter Study
Authors: Habib Joseph R. , Kinny-Köster Benedict , Javed Ammar A. , Zelga Poitr , Saadat Lily V. , Kim Rachel C. , Gorris Myrte , Allegrini Valentina , Watanabe Shuichi , Sharib Jeremy , Arcerito Massimo , Kaiser Jörg , Lafaro Kelly J. , Tu Min , Bhandre Manish , Shi Chanjuan , Kim Michael P. , Correa Camilo , Daamen Lois A. , Oberstein Paul E. , Schmidt C. Max , Hanna Nader N. , Allen Peter , Loos Martin , Shrikhande Shailesh V. , Molenaar I. Quintus , Frigerio Isabella , Katz Matthew H.G. , Soares Kevin C. , Miao Yi , Del Chiaro Marco , He Jin , Hackert Thilo , Salvia Roberto , Büchler Markus W. , Castillo Carlos Fernandez-del , Besselink Marc G. , Marchegiani Giovanni , Wolfgang Christopher L. ,   for the Verona IPMN Consortium, Prakash Laura R. , Grewal Mahip , Pea Antonio , Butturini Giovanni , Hecker Max , van Oosten Floortje 
Published: September 2024

PURPOSE
The benefit of adjuvant therapy for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) remains unclear because of severely limited evidence. Although biologically distinct entities, adjuvant therapy practices for IPMN-derived PDAC are largely founded on pancreatic intraepithelial neoplasia-derived PDAC. We aimed to evaluate the role of adjuvant chemotherapy in IPMN-derived PDAC.

METHODS
This international multicenter retrospective cohort study (2005-2018) was conceived at the Verona Evidence-Based Medicine meeting. Cox regressions were performed to identify risk-adjusted hazard ratios (HR) associated with overall survival (OS). Kaplan-Meier curves and log-rank tests were employed for survival analysis. Logistic regression was performed to identify factors motivating adjuvant chemotherapy administration. A decision tree was proposed and categorized patients into overtreated, undertreated, and optimally treated cohorts.

RESULTS

In 1,031 patients from 16 centers, nodal disease (HR, 2.88,
P
< .001) and elevated (≥37 to <200 µ/mL, HR, 1.44,
P
= .006) or markedly elevated (≥200 µ/mL, HR, 2.53,
P
< .001) carbohydrate antigen 19-9 (CA19-9) were associated with worse OS. Node-positive patients with elevated CA19-9 had an associated 34.4-month improvement in median OS (
P
= .047) after adjuvant chemotherapy while those with positive nodes and markedly elevated CA19-9 had an associated 12.6-month survival benefit (
P
< .001). Node-negative patients, regardless of CA19-9, did not have an associated benefit from adjuvant chemotherapy (all
P
> .05). Based on this model, we observed undertreatment in 18.1% and overtreatment in 61.2% of patients. Factors associated with chemotherapy administration included younger age, R1-margin, poorer differentiation, and nodal disease.

CONCLUSION
Almost half of patients with resected IPMN-derived PDAC may be overtreated or undertreated. In patients with node-negative disease or normal CA19-9, adjuvant chemotherapy is not associated with a survival benefit, whereas those with node-positive disease and elevated CA19-9 have an associated benefit from adjuvant chemotherapy. A decision tree was proposed. Randomized controlled trials are needed for validation.