Adjuvant Chemotherapy Is Associated with Improved Survival in Advanced Ampullary Adenocarcinoma—A Population-Based Analysis by the German Cancer Registry Group

<b>Introduction</b>: Ampullary adenocarcinomas (AMPACs) represent rare malignant neoplasms arising in the Ampulla of Vater. Due to a lack of prospective studies and heterogeneous results from retrospective analyses, the outcomes of adjuvant chemotherapy (AC) in AMPAC are unclear. <b>Methods</b>: Pooled, pseudonymized data were retrieved from clinical cancer registries participating in the German Cancer Registry Group of the Association of German Tumor Centers (GCRG/ADT). Patients who underwent surgical resection of AMPACs (ICD-10: C24.1) with subsequent follow-up or AC were included. Patients with 90-day postoperative mortality were excluded. The epidemiologic and histopathologic features as well as the overall survival and recurrences were compared in both groups using R statistics. <b>Results</b>: In total, 830 patients with AMPACs were identified, of which 184 (22.2%) received AC. The surgery + AC patients showed more advanced tumor stages and more pronounced locoregional invasion as compared to the group undergoing surgery alone. AC was independently associated with an improved overall survival (OS) in a multivariable analysis (HR 0.57, <i>p</i> < 0.001), where pT3-4 status, lymph node metastases, vascular invasion, and advanced grading remained independent prognostic factors for OS. In the subgroup analyses, AC was associated with improved OS in the patients with pT3-4 tumors, lymph node metastases, lymphovascular invasion, and advanced grading, or UICC stage III, whereas no association with the OS was observed in the other subgroups. AC was also associated with superior disease-free survival (DFS) in a multivariable analysis. <b>Conclusions</b>: We provide a large-scale population-based analysis of AMPAC patients, showing an association of AC with improved OS in patients with advanced-staged disease or signs of locoregional invasion as compared to surgery alone.