Safety Considerations in Grade 3 Disease

Faculty examine the safety considerations most important when treating grade 3 neuroendocrine tumors, beginning with the recently defined and still-evolving nature of this category. The panel emphasizes that Ki-67 represents a continuum without a defined upper threshold, and that morphology and differentiation must be carefully assessed. Speakers identify expert pathology review as the foremost safety consideration, noting that tumors initially labeled grade 3 are sometimes reclassified as large cell neuroendocrine carcinoma or downgraded, fundamentally altering treatment. Disease trajectory is also stressed, with faculty advocating close monitoring and earlier treatment initiation in higher-grade disease. The discussion turns to therapy selection, weighing cabozantinib against capecitabine plus temozolomide and other chemotherapy, with several favoring chemotherapy at higher Ki-67 levels while acknowledging the absence of a definitive cutoff. Differentiation status, functional imaging including FDG and dotatate PET, and molecular markers such as p53 and RB loss inform these individualized decisions.