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; Verona IPMN Consortium
J Clin Oncol . 2024 Sep 10:JCO2302313. doi: 10.1200/JCO.23.02313. Online ahead of print.
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.