Identifying occult high-risk features and stratified management strategies following curative resection for ampullary adenocarcinoma

The aim of the current study was to identify independent prognostic factors, evaluate differential adjuvant chemotherapy efficacy across clinicopathologic subgroups, and define adjuvant chemotherapy-sensitive populations.

A retrospective analysis of 168 AAC patients undergoing curative pancreaticoduodenectomy (2011–2020) was performed. Cases were classified into intestinal (28.0%), pancreatobiliary (30.4%), and mixed subtypes (18.5%) per NCCN (v2.2025) criteria. Independent prognostic factors for AAC patients were identified through uni- and multi-variable Cox proportional hazards modeling and subgroup analyses were stratified by age range, gender, differentiation, T stage, N stage, BVI, TDs, and PNI.

The pancreatobiliary signature (HR = 2.884, P < 0.001) and BVI (HR = 2.330, P = 0.001) were independent poor prognostic factors. Adjuvant chemotherapy improved overall survival (OS) in the following AAC patients: T3–T4 stage (HR = 0.485, P = 0.050); N1–N2 stage (HR = 0.365, P = 0.008); and TD-positive (HR = 0.401, P = 0.026). The median OS increased from 22.3–51.3 months with adjuvant chemotherapy in TD-positive patients (P = 0.019). TD positivity conferred a worse prognosis in BVI-negative subgroups (OS: HR = 3.840, 95% CI: 2.058–7.166, P < 0.001; and progression-free survival (PFS): HR = 2.950, 95% CI: 1.550–5.617, P = 0.002).

The pancreatobiliary signature and BVI constitute critical high-risk pathologic features in AAC. TD status identified high-risk cohorts, thus enabling postoperative risk-stratified treatment strategies. In patients negative for pancreatobiliary signature or BVI, TD positivity predicted significantly worse survival.