Incidence, clinical management and prognosis of patients with small intestinal adenocarcinomas from 1999 through 2019: A nationwide Dutch cohort study

Background: Small intestinal adenocarcinomas (SIAs) are rare. Hence, randomized controlled trials are lacking and understanding of the disease features is limited. This nationwide cohort investigates incidence, treatment and prognosis of SIA patients, to improve disease outcome. Patients and methods: Data of 2697 SIA patients diagnosed from January 1999 through December 2019 were retrieved from the Netherlands Cancer Registry and Pathology Archive. Incidence was calculated using the revised European Standardized Rate. The influence of patient and tumor characteristics on overall survival (OS) was studied using survival analyses. Results: The age-standardized incidence rate almost doubled from 0.58 to 1.06 per 100,000 person-years, exclusively caused by an increase in duodenal adenocarcinomas. OS did not improve over time. Independent factors for a better OS were a younger age, jejunal tumors, Lynch syndrome and systemic therapy. Only 13.8% of resected patients was treated with adjuvant chemotherapy, which improved OS compared to surgery alone in stage III disease (HR 0.47 (0.35–0.61)), but not in the limited group of deficient mismatch repair (MMR) patients (n = 53, HR 0.93 (0.25–3.47)). In the first-line setting, CAPOX was associated with improved OS compared to FOLFOX (HR 0.51 (0.36–0.72)). For oligometastatic patients, a metastasectomy significantly improved OS (HR 0.54 (0.36–0.80)). Conclusions: The incidence of SIAs almost doubled in the past 20 years, with no improvement in OS. This retrospective non-randomized study suggests the use of adjuvant chemotherapy for stage III disease and first-line CAPOX for metastatic patients. For selected oligometastatic patients, a metastasectomy may be considered. MMR-status testing could aid in clinical decision-making.