Gastric Neuroendocrine Tumors (g-NETs): A Systematic Review of the Management and Outcomes of Type 3 g-NETs

Simple Summary Gastric well-differentiated neuroendocrine tumors (g-NETs) occur in 5-15% of cases of neuroendocrine neoplasms in the gastrointestinal tract, and they mostly present quite indolent biological behavior. Furthermore, among the g-NETs, the type 3 versions represent the most aggressive subcategory, with the highest incidence of lymph-vascular infiltration and metastases at diagnosis. For these reasons, a more interventional approach to the management of type 3 g-NETs has been generally shared by the scientific community. However, a case-by-case discussion amongst a multidisciplinary NET-dedicated team revealed that partial or complete gastrectomy with lymphadenectomy had become an out-of-proportion indication within such cases regarding small and/or low-grade lesions. The aim of this systematic review was to assess the real-life approaches to type 3 g-NETs and identify some of the prognostic factors that might impact management choices. We found that size and gastric wall infiltration and grading may represent three factors that should be taken into account to better manage type 3 g-NETs. Purpose: to collect data from real-life experiences of the management of type 3 g-NETs and identify possible prognostic factors that may impact the decision-making process. Methods: We performed a systematic review of the literature on type 3 g-NET management using the PubMed, MEDLINE, and Embase databases. We included cohort studies, case series, and case reports written in the English language. Results: We selected 31 out of 556 articles from between 2001 and 2022. In 2 out of the 31 studies, a 10 mm and 20 mm cut-off size were respectively associated with a higher risk of gastric wall infiltration and/or lymph node and distant metastasis at diagnosis. The selected studies reported a higher risk of lymph node or distant metastasis at diagnosis in the case of muscularis propria infiltration or beyond, irrespective of the dimensions or grading. From these findings, size, grading, and gastric wall infiltration seem to be the most relevant factors in management staff making choices and prognoses of type 3 g-NET patients. We produced a hypothetical flowchart for a standardized approach to these rare diseases. Conclusion: Further prospective analyses are needed to validate the prognostic impact of the use of size, grading, and gastric wall infiltration as prognostic factors in the management of type 3 g-NETs.