过去几十年来，管状胃肠道 (GI) 和胰腺中出现的神经内分泌肿瘤 (NEN) 的分类和治疗取得了显着进展。在 2022 年发布的最新 WHO 分类中，无论 NEN 的主要来源如何，都将其分为两大类：高分化神经内分泌肿瘤 (NET) 和低分化神经内分泌癌 (NEC)。分级系统的重大变化改变了3级的定义，包括高等级高分化NET（G3-NET）和低分化NEC（-NEC）。尽管这两个亚组被认为是高级别的，Ki-67 > 20%，但它们具有不同的基因组谱、预后和临床行为，这严重影响了它们的治疗策略。用于指导这些高级别亚组治疗的可用临床试验数据极其有限，这影响了其管理。在这篇综述中，我们将总结当前在管理高级 GEP-NEN（包括 G3-NET 和 NEC）的多学科方法方面取得的进展。

The classification and management of neuroendocrine neoplasms (NENs) arising in the tubular gastrointestinal (GI) tract and pancreas have significantly evolved over the last decades. In the latest WHO classification published in 2022, NEN are separated regardless of their primary origin into two main groups: well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The substantial changes in grading system changed the definition of grade 3 to include high grade well differentiated NETs (G3-NETs), and poorly differentiated NECs (-NECs). Although, these two subgroups are considered high grades with Ki-67 >20%, they have different genomic profiles, prognosis and clinical behavior which critically influence their treatment strategies. The available clinical trial data to guide therapy of these high-grade subgroups are extremely limited which impact their management. In this review, we will summarize the current advances in the multidisciplinary approach for management of high grade GEP-NENs including G3-NETs and NECs.