Abstract
Duodenal cancer, a rare gastrointestinal malignancy (30%-45% of small bowel cancers), shows improved outcomes with multidisciplinary advances. Endoscopic resection is preferred for early-stage (Tis/T1) tumors (66% usage), enhancing survival (hazard ratio [HR]: 0.70) and reducing infection-related mortality vs surgery (P = 0.03). Advanced cases rely on surgical resection (segmental/Whipple, 46.4% 5-year survival) with minimally invasive techniques reducing blood loss. Poor prognosis links to nodal metastasis (HR: 2.58) and vascular invasion (HR: 2.18). Patients with stage III disease benefit from FOLFOX chemotherapy (HR: 0.55), while neoadjuvant chemoradiotherapy improves resectability. Targeted therapies (erb-b2 receptor tyrosine kinase 2/epidermal growth factor receptor/phosphatidylinositol-3-kinase-protein kinase B-mechanistic target of rapamycin kinase) yield complete responses with trastuzumab-chemotherapy combinations. Immunotherapy (pembrolizumab) achieves organ preservation in microsatellite instability-high/mismatch repair-deficient locally advanced tumors. Molecular profiling (caudal type homeobox 2, cell-free DNA, microsatellite instability) guides personalized therapy. Future priorities include global collaborations for precision strategies and novel biomarkers, integrating surgical, targeted, and immunotherapeutic advances to optimize survival and quality of life.