High-grade gastroenteropancreatic neuroendocrine neoplasms (WHO 3) have a Ki-67>20% and are well-differentiated neuroendocrine tumors (NET G3) or poorly-differentiated neuroendocrine carcinomas (NEC). NEC originate anywhere in the gastroenteropancreatic tract, whereas NET G3 are mainly pancreatic and have a much better prognosis than NEC.
An aggressive approach is scheduled with localized disease as many can be cured. Adjuvant therapy is recommended after radical surgery of NEC. Metastatic NEC is usually treated with platinum-based chemotherapy and etoposide, with a response rate of 30-40%, progression-free survival 4-6 months and median survival 8-13 months. No differences are seen comparing cisplatin- to carboplatin-based chemotherapy. Neoplasms with a Ki-67<55% are less responsive to platinum-based chemotherapy, but have a significant longer survival. Small studies show some benefit of 2nd-line chemotherapy. NET G3 patients do not respond to platinum-based chemotherapy and other treatment alternatives should be considered. PRRT may be an evolving therapy in selected NEN G3 patients.