Despite advances in cancer care, treatment strategies for ampullary adenocarcinoma (AAC) remain uncertain. Its anatomic location and biological diversity lead to variable clinical behavior and outcomes. While curative pancreaticoduodenectomy is the standard therapy, recurrence affects nearly half of all patients, and the benefits of postoperative chemotherapy remain debated. Conventional prognostic markers, such as lymph node status and differentiation, fail to fully capture hidden high-risk features. Based on these challenges, it is necessary to explore clinicopathological factors that predict survival and treatment benefit in AAC, to develop more effective and individualized postoperative management.
A research team from Tianjin Medical University Cancer Institute & Hospital has provided new insights into postoperative risk stratification for AAC. The study, published (DOI: 10.20892/j.issn.2095-3941.2025.0181) on October 2025 in Cancer Biology & Medicine, analyzed long-term outcomes in 168 patients following curative resection. The researchers identified tumor deposits as a pivotal marker predicting who benefits from adjuvant chemotherapy, and defined the pancreatobiliary signature and blood vessel invasion as key independent prognostic features guiding clinical decision-making.
Using multivariate Cox regression and subgroup analyses, the team evaluated how clinicopathological features influence overall and progression-free survival in AAC. They found that patients with the pancreatobiliary signature (CDX2−/MUC1+) and those showing blood vessel invasion had significantly poorer outcomes, marking these as independent high-risk factors. Importantly, tumor deposits—clusters of tumor cells in soft tissue disconnected from the primary lesion—emerged as a crucial context-dependent biomarker. While not an independent prognostic factor overall, tumor deposit–positive patients experienced a 60% reduction in mortality risk when treated with adjuvant chemotherapy. Their median overall survival rose from 22.3 to 51.3 months. This benefit was most evident among patients with advanced-stage tumors, lymph node metastasis, or absence of blood vessel invasion. The findings suggest that identifying tumor deposits can help clinicians tailor adjuvant chemotherapy to those most likely to respond, bridging a critical evidence gap in AAC management.
"Given the rarity and heterogeneity of AAC, optimizing treatment requires precise understanding of its pathology," said Professor Jihui Hao of Tianjin Medical University Cancer Institute & Hospital. "Our findings reveal that tumor deposits serve as a hidden indicator of recurrence risk and chemotherapy responsiveness. Recognizing these features allows clinicians to identify patients who can truly benefit from postoperative therapy and avoid unnecessary treatment in others, moving toward precision oncology for this uncommon yet aggressive disease."
This study provides actionable evidence for refining postoperative strategies in AAC, aligning with recent updates to the NCCN guidelines. By integrating tumor deposit assessment into routine pathological evaluation, oncologists can better stratify patients for adjuvant chemotherapy, improving survival while minimizing overtreatment. The proposed model of risk-adapted management could serve as a template for precision care in other gastrointestinal cancers with similar biological diversity. Future multicenter and prospective studies will be essential to validate these findings and further develop evidence-based guidelines for this rare disease.
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References
DOI
10.20892/j.issn.2095-3941.2025.0181
Original Source URL
https://doi.org/10.20892/j.issn.2095-3941.2025.0181
Funding information
This work was supported by the National Key Research and Development Program of China (Grant No. 2021YFA1201100), the Projects of Tianjin Science and Technology Bureau National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine (Grant Nos. 24ZXZSSS00440 and 22ZXJBSY00030), the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (Grant No. 2022ZD067), and the Tianjin Key Medical Discipline (Specialty) Construction Project (Grant No. TJYXZDXK-009A).
About Cancer Biology & Medicine
Cancer Biology & Medicine (CBM) is a peer-reviewed open-access journal sponsored by China Anti-cancer Association (CACA) and Tianjin Medical University Cancer Institute & Hospital. The journal monthly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China. The journal is indexed in SCOPUS, MEDLINE and SCI (IF 8.4, 5-year IF 6.7), with all full texts freely visible to clinicians and researchers all over the world.