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 to characterize clinicopathological features, treatment approaches, and survival outcomes, and to explore potential prognostic factors. Kaplan–Meier analysis was used to estimate recurrence-free survival (RFS) and overall survival (OS), while prognostic factors were assessed using univariate and multivariable Cox regression models. Results: Most patients presented with resectable disease and underwent pancreaticoduodenectomy (96.2%). The predominant histological 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. In univariate analyses, adverse prognostic factors for both RFS and OS included the advanced T TNM category, nodal involvement, lymphovascular invasion, perineural invasion, high-grade histology, and R1 resection margins; however, only R1 resection margin remained independently associated with shorter RFS in the multivariate analysis (HR 2.5, 95% CI 1.02–5.94, p = 0.046). Survival outcomes did not differ significantly according to histological subtype. Exploratory adjusted analyses accounting for nodal status and surgical resection margin suggested an association between adjuvant therapy and improved survival, while unadjusted analyses showed no significant associations. Median OS for metastatic patients was 13.6 months. Discussion/Conclusion: R1 resection margin emerged as the only independent prognostic factor for RFS, with no independent association with OS, in resected AC. These findings highlight the importance of surgical margin optimization, high-quality pathological assessment, and multidisciplinary management in routine clinical practice.
Furtado et al. (Sun,) studied this question.