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Life sciences · Journal article
Current Oncology Reports · September 16, 2026
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This review highlights the major unmet needs in diagnosis and treatment of digestive neuroendocrine carcinomas (NEC) and describes the current and evolving evidence on these aspects. Improved pathological criteria are needed to accurately diagnose NEC and distinguish this entity from high-grade well-differentiated neuroendocrine tumours as well as from adenocarcinoma. Studies on the molecular mechanisms underlying the extreme aggressiveness of the disease are ongoing. Data are lacking on optimal selection of patients with locoregional disease for primary tumour surgery and use of adjuvant or neoadjuvant treatment. For patients with metastatic disease, there has been no improvement in systemic treatment over the last two decades and immunotherapy has limited benefit. Novel antigen-directed strategies targeting DLL3 are evolving. Digestive NEC are among the most aggressive cancers and prognosis remains poor. There have been only minor improvements over the last two decades. To improve diagnosis and therapy, the unmet needs discussed in this review must be addressed.