Histopathologic predictors of survival and recurrence in resected ampullary adenocarcinoma: International multicenter cohort study

Abstract

Background: A broad range of survival rates have been described for adenocarcinoma of the ampulla of Vater, presumably due to morphological heterogeneity which is a result of the different epitheliums AAC can arise from (intestinal or pancreaticobiliary). Large series with homogenous patient selection are scarce. The aim of the study was to define histopathologic characteristics that independently predict overall survival (OS) and disease-free survival (DFS), in patients who underwent resection of an ampullary adenocarcinoma (AAC) with curative intent. Methods: A retrospective multicenter cohort analysis of patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma in nine European tertiary referral centers between February 2006 and December 2017, was performed. Collected data included demographics, histopathologic details, survival and recurrence. OS and DFS analyses were performed using Kaplan-Meier curves and Cox proportional hazard models. Results: Overall, 887 patients were included, with a mean age of 66 ± 10 years. The median OS was 64 months with 1-, 3-, 5- and 10-year OS rates of 89%, 63%, 52% and 37%, respectively. Histopathologic subtype, differentiation grade, lymphovascular invasion, perineural invasion, T-stage, N-stage, resection margin and adjuvant chemotherapy were correlated with OS and DFS. N-stage (HR = 3.30 [2.09 – 5.21]), perineural invasion (HR = 1.50 [1.01 – 2.23]) and adjuvant chemotherapy (HR = 0.69 [0.48 – 0.97]) were independent predictors of OS in multivariable analysis, whereas DFS was only adversely predicted by N-stage (HR = 2.65 [1.65 – 4.27]). Sensitivity analysis performed in this study, revealed adjuvant chemotherapy was only an independent predictor of increased OS in the 293 patients with pancreaticobiliary subtype (HR = 0.61 [0.40 – 0.93, p = 0.023) but not for the 211 patients with intestinal subtype (HR = 1.06 [0.57 – 1.95], p=0.861). Conclusion: Unfavorable predictors of OS were LN involvement and perineural invasion. Whereas, adjuvant chemotherapy independently predicted improved OS. DFS was independently predicted by LN involvement. Sub-analysis of the histopathologic subtypes revealed that patients with the pancreaticobiliary subtype benefit from adjuvant chemotherapy in terms of survival, whereas patients with intestinal histopathologic subtype did not.