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Life sciences · Journal article
Frontiers in Oncology · September 18, 2026
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Background Ampullary cancer presents unique clinical challenges due to its rarity and diagnostic complexities. Current data addressing ampullary cancer therapy are limited. This retrospective study focused on advanced disease and explored the rational therapeutic strategies especially based on histopathological subtype, which maybe provide evidence-based guidance for this understudied malignancy. Methods We enrolled advanced ampullary cancer patients from two centers. Clinicopathological data and treatment details were collected. Treatment outcome comparisons between different chemotherapeutic regimens (gemcitabine-based vs fluorouracil-based) and different histopathologic types (Pancreaticobiliary vs Non-pancreaticobiliary) were conducted. Results 71 patients with advanced ampullary cancer were enrolled. Elevated CA19–9 was observed in 63.4% (45/71). Postoperative metastasis occurred in 90.1% (64/71) patients. Histological subtyping was feasible in 43 patients, including 38 pancreaticobiliary, 4 intestinal, and 1 mixed subtype. All patients received first-line chemotherapy with objective response rate (ORR) of 19.7%, median progression-free survival (mPFS) of 9.6 months and median overall survival (mOS) of 33.2 months. Comparable efficacy between gemcitabine-based group (n=27) and fluorouracil-based group (n=44) (ORR 14.8% vs 22.7%, mPFS 6.67 months vs 11.20 months, mOS 26.70 months vs 38.90 months, p>0.05) were observed. Pancreatobiliary subgroup (n=38) exhibited ORR of 15.8%, median PFS of 8.33 months, and OS of 31.7 months, and 20% ORR, 9.93-month PFS, and 32.3-month OS in non-pancreatobiliary cases (n=5). Conclusions Advanced ampullary cancer demonstrates aggressive behavior and poor chemotherapy responses. No formal statistical comparison was performed between histopathological subtypes due to the small sample size of the non-pancreatobiliary group. However, the number of patients with the pancreatobiliary-type was far greater than that with the non-pancreatobiliary-type. Due to the underrepresentation of non-pancreatobiliary-type cases, the predictive value of histopathological subtyping in advanced disease could not be adequately assessed.