Chemotherapy in Well Differentiated Neuroendocrine Tumors (NET) G1, G2, and G3: A Narrative Review

Neuroendocrine tumors (NETs) are rare neoplasms with a wide spectrum of clinical behavior, from the long survival of well-differentiated NETs to the dismal prognosis of high-grade neuroendocrine carcinomas (NECs), being G3 NETs a recently recognized intermediate entity. While the role of chemotherapy is well established in NECs, data on NETs mostly derives from small studies, experts' opinions, and extrapolating results from small-cell lung cancer studies. This narrative review aims to summarize available evidence about the use of chemotherapy in the setting of G1-2 NETs and G3 NETs. We performed literature research in PubMed Library for all articles published up to September 2022 about the efficacy of chemotherapy in NETs. Treatment regimens with STZ-5FU, CAPTEM, and anti-metabolite-based treatment are the most active and tolerated in gastroenteropancreatic NETs (GEP-NETs) G1-G2, while platinum-based regimens (FOLFOX/XELOX) and TEM/CAPTEM showed the best activity in thoracic NETs. Solid evidence about chemotherapy efficacy in G3 NETs is still lacking. Literature data support the use of chemotherapy in low-intermediate grade NETs after the failure of other therapies or if tumor shrinkage is needed. Studies assessing G3 NETs independently from NECs are needed to better understand the role of chemotherapy in this setting.

Automated summary

Neuroendocrine tumors (NETs) have diverse clinical behaviors, ranging from long survival in well-differentiated NETs to poor prognosis in high-grade neuroendocrine carcinomas (NECs). The use of chemotherapy in NECs is well established, but data on NETs is limited and mainly derived from small studies and expert opinions. This review aims to summarize the available evidence on chemotherapy in G1-2 NETs and G3 NETs. While specific treatment regimens have shown efficacy in gastroenteropancreatic NETs (GEP-NETs) and thoracic NETs, solid evidence on the efficacy of chemotherapy in G3 NETs is still lacking. Further studies are needed to better understand the role of chemotherapy in this setting.