Management of high-grade neuroendocrine neoplasms: impact of functional imaging

Gastroenteropancreatic neuroendocrine neoplasms(GEP NEN) exhibit substantial biological heterogeneity, impacting clinical management and outcomes. In 2019, the WHO introduced the neuroendocrine tumour(NET) grade 3 (G3) subgroup, characterized by Ki-67>20% and a well-differentiated morphology and poorly differentiated neuroendocrine carcinomas(NEC) (Ki-67>20%). Since this update, questions about the prognostic implications and best treatment strategies for NET G3 and NEC remain. Therefore we initiated a real-world retrospective observational cohort study, using data from 225 NEC and 58 NET G3 patients treated in Belgium. Analysis of patient and tumour characteristics and the effect of survival was conducted. Most frequent primary locations were pancreatic (32.9%) and colorectal (21.5%), and 71.8% was diagnosed with stage IV disease. Median overall survival(mOS) was higher in NET G3 (41.3 months(m)) compared to NEC (13.2m). Of those who underwent functional imaging, fluorodeoxyglucose-positron emission tomography-imaging (18F-FDG-PET) was positive in 90.6% and 95.6% of the NET G3 and NEC patients, respectively, and somatostatin receptor(SSTR) expression was seen in 97.4% and 66.0%, respectively. The latter was linked to a better mOS, suggesting the added value of performing both SSTR imaging and 18F-FDG-PET for high grade(HG) NEN to provide prognostic information and to possibly expand to therapeutic options which are currently reserved for lower-grade NEN patients. Moreover, while debated, in our population primary surgery was performed in 92% and 73.5% of locoregional NET G3 and NEC cases respectively, indicating that surgery can be considered in locoregional setting. Finally, platinum-etoposide was the predominant first-line treatment in metastatic NEC, with no significant survival difference between carboplatin and cisplatin.