Neoadjuvant Therapy for Duodenal and Ampullary Adenocarcinoma: A Systematic Review

Background: The role of systemic therapy in the management of ampullary (AA) and duodenal adenocarcinoma (DA) remains poorly understood. This study sought to synthesize current evidence supporting the use of neoadjuvant therapy (NAT) in AA and DA. Methods: The study searched PubMed, Cochrane Library (Wiley), Embase (Elsevier), CINAHL (EBSCO), and ClinicalTrials.gov databases for observational or randomized studies published between 2002 and 2022 evaluating survival outcomes for patients with non-metastatic AA or DA who received systemic therapy and surgical resection. The data extracted included overall survival, progression-free survival, and pathologic response (PR) rate. Results: From the 347 abstracts identified in this study, 29 reports were reviewed in full, and 15 were included in the final review. The selected studies published from 2007 to 2022 were retrospective. Eight were single-center studies; five used the National Cancer Database (NCDB); and two were European multicenter/national studies. Overall, no studies identified survival differences between NAT and upfront surgery (with or without adjuvant therapy). Two NCDB studies reported longer survival with NAT/AT than with surgery. Five single-center studies reported a significant portion of NAT patients who achieved PR, and one study identified major PR as an independent predictor of survival. Other outcomes associated with NAT included conversion from unresectable to resectable disease, reduced lymph node positivity, and decreased local recurrence rate. Conclusion: Evidence supporting the use of NAT in AA and DA is weak. No randomized studies exist, and observational data show mixed results. For patients with DA and AA, NAT appears safe, but better evidence is needed to understand the preferred multidisciplinary management of DA and AA periampullary malignancies.