Impact of Adjuvant Chemotherapy on Resected Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Cancer: Results From an International Multicenter Study
Authors: Joseph R. Habib, Benedict Kinny-Köster, Ammar A. Javed, Poitr Zelga, Lily V. Saadat, Rachel C. Kim, Myrte Gorris, Valentina Allegrini, Shuichi Watanabe, Jeremy Sharib, Massimo Arcerito, Jörg Kaiser, Kelly J. Lafaro, Min Tu, Manish Bhandre, Chanjuan Shi, Michael P. Kim, Camilo Correa, Lois A. Daamen, Paul E. Oberstein, C. Max Schmidt, Nader N. Hanna, Peter Allen, Martin Loos, Shailesh V. Shrikhande, I. Quintus Molenaar, Isabella Frigerio, Matthew H.G. Katz, Kevin C. Soares, Yi Miao, Marco Del Chiaro, Jin He, Thilo Hackert, Roberto Salvia, Markus W. Büchler, Carlos Fernandez-del Castillo, Marc G. Besselink, Giovanni Marchegiani, Christopher L. Wolfgang, Laura R. Prakash, Mahip Grewal, Antonio Pea, Giovanni Butturini, Max Hecker, Floortje van Oosten
Journal: Journal of Clinical Oncology (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 &lt; .001) and elevated (≥37 to &lt;200 µ/mL, HR, 1.44, P = .006) or markedly elevated (≥200 µ/mL, HR, 2.53, P &lt; .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 &lt; .001). Node-negative patients, regardless of CA19-9, did not have an associated benefit from adjuvant chemotherapy (all P &gt; .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.