Abstract

Introduction: Neoadjuvant therapy (NT) is increasingly used prior to surgery for localized pancreatic ductal adenocarcinoma (PDAC). Given the importance of completing multimodality therapy, we sought to characterize rates and reasons for failing to undergo pancreatectomy following contemporary NT. Methods: A systematic review and meta-analysis of prospective trials and intention-to-treat retrospective studies since 2010 was performed to summarize rates of NT completion, surgical exploration, overall resection, and R0 resectionfollowing neoadjuvant chemotherapy and/or chemoradiation for potentially resectable (PR), borderline resectable (BR) and locally advanced (LA) disease. Pooled results were calculated using mixed effect models with restricted maximum likelihood estimation. Results: Of 117 studies that met inclusion criteria, 15 were randomized controlled trials, 62 nonrandomized prospective studies, and 40 retrospective cohort studies. NT consisted of chemotherapy alone (35.0%), chemoradiation alone (10.3%), or chemotherapy and radiation (54.7%). Among 11,147 patients, the pooled overall resection rates were 76.9%, 59.5%, and 30.0% for PR, BR, and LA PDAC, respectively. Rates of NT completion, exploration, and R0 resection rates (Figure 1a) and reasons for failing to undergo resection (Figure 1b) varied based on anatomic stage. Conclusion: In this meta-analysis of intention-to-treat studies, rates and reasons for failing to undergo pancreatectomy following NT vary based on anatomic stage. These pooled resection rates may inform patients and providers on the likelihood to attain surgical resection following NT for PR, BR, and LA PDAC and will serve as important benchmarks for future prospective trials. Future research should identify opportunities to decrease attrition and optimize outcomes of NT for PDAC.

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