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.