Histopathologic Subtype as a Determinant of Prognosis and Chemotherapy Benefit in Resected Ampullary Adenocarcinoma

Ampullary adenocarcinoma (AAC) is a rare malignancy with heterogeneous biological behavior. Although surgical resection is the only potentially curative option, the prognostic role of histopathologic features and adjuvant chemotherapy (AC) remains unclear.

Consecutive patients undergoing curative-intent pancreatoduodenectomy for AAC at the University of Colorado Hospital between January 2013 and May 2025 were retrospectively reviewed. Clinicopathologic variables associated with overall (OS) and recurrence-free survival (RFS) were analyzed using multivariable Cox regression.

Ninety-seven patients were included. Median OS was 93.9 months with 1-, 3-, 5-, and 10-year OS rates of 89%, 67%, 59%, and 46%. Older age (HR, 3.79; 95% CI, 1.71-8.41), lymph node (LN) involvement (HR, 4.92; 95% CI, 1.87-12.93), and R1 margin (HR, 4.33; 95% CI, 1.09-17.25) independently predicted poorer OS. The pancreatobiliary subtype (pbAAC) showed worse OS than the intestinal subtype (iAAC) (5-year OS, 48% vs. 75%; p = 0.012). In pbAAC, LN metastasis (HR, 4.16; 95% CI, 1.31-13.18) and R1 margin (HR, 5.47; 95% CI, 1.10-27.20) predicted worse OS, whereas AC was associated with improved survival (HR, 0.404; 95% CI, 0.18-0.91). No AC benefit was observed in iAAC (p = 0.323).

Histopathologic subtype is a key prognostic factor in AAC, with AC associated with better survival in pbAAC.