The Evolving Treatment Algorithm for Advanced Neuroendocrine Neoplasms: Diversity and Commonalities Across Tumor Types

Neuroendocrine neoplasms (NEN) most commonly arise in the gastroenteropancreatic system and lungs. The incidence of NEN is increasing globally, with improved diagnostic techniques identifying patients with early-stage disease. The number of approved therapies for the treatment of advanced disease has grown substantially in the past decade. The treatment algorithm for advanced NEN is evolving from one that is directed by primary site-specific classification to one that is directed by biologic classification, as evidenced by overlapping systemic treatments across the primary tumor sites. Commonalities in biologic characteristics across primary sites include functional status, differentiation status, grade, level of somatostatin receptor expression, and genetic alterations. In this review, we discuss current clinical evidence and available therapies for the treatment of advanced NEN and highlight the need for prospective trials in patients with well-differentiated, high-grade NEN. IMPLICATIONS FOR PRACTICE: This review raises awareness of the evolution of the treatment algorithm for advanced neuroendocrine neoplasms (NEN) from one that is directed by primary tumor site-specific classification to one that is directed by biologic classification. In addition, this review promotes understanding of the new pathologic category of well-differentiated G3 pancreatic neuroendocrine tumors and highlights the need for prospective trials in this patient population, for whom there is currently no standard of care. This review further provides a conceptual treatment schematic that categorizes the recommendations for systemic treatments for advanced disease by biologic classification, including the new and established categories of NEN.