Ampullary Carcinoma: Prognostic Factors and a Literature Review

Background/ Objectives: Ampullary carcinoma (AC) is a rare gastrointestinal malignancy arising from the ampullary complex, encompassing intestinal, pancreaticobiliary, and mixed subtypes with distinct biological behaviors. Surgery is the only potentially curative treatment, yet relapse occurs in more than half of patients. Due to the scarcity of AC-specific prospective trials, treatment guidelines are largely extrapolated from other gastrointestinal cancers. This study aimed to characterize the clinicopathological features, treatment approaches, and outcomes of AC, and to identify potential prognostic factors in a single-center cohort. Methods: We retrospectively analyzed 106 patients diagnosed with AC between January 2015 and December 2023. Clinical, pathological, and treatment data were extracted from institutional records. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and prognostic factors were assessed through univariate and multivariate Cox regression analyses. Results: Most presented with resectable disease and underwent curative-intent surgery (96.2%). The predominant histologic subtype was pancreaticobiliary (45.3%). In localized disease, median RFS and OS were not reached, with 36-month RFS and OS rates of 68.1% (95% CI, 59.2–78.3) and 70.1% (95% CI, 61.1–80.3), respectively. Adverse prognostic factors for both RFS and OS included advanced T stage, nodal involvement, lymphovascular invasion, perineural invasion, high-grade histology, and R1 resection margins; however, only R1 margin remained independently associated with shorter RFS in the multivariate analysis (HR 2.5, 95% CI 1.02–5.94, p = 0.046). Adjuvant therapy and intestinal subtype showed trends toward improved survival, without statistical significance. Median OS for metastatic patients was 13.6 months. Discussion/Conclusion: R1 resection margin emerged as the only independent prognostic factor for recurrence in resected AC. These results underscore the importance of meticulous pathology and multidisciplinary management, supporting individualized treatment strategies.