Understanding extrapulmonary neuroendocrine carcinomas: Survival, prognosis, and patient quality of life

Extrapulmonary neuroendocrine carcinomas (epNECs) are high-grade malignancies that arise from various anatomic sites and follow an aggressive clinical course. Most patients with epNEC present with metastatic disease at diagnosis and face a dismal prognosis, surviving less than a year. Despite treatment, disease progression is common and most patients rapidly succumb to the disease, which may limit participation in prospective clinical trials. Given the grim survival outcomes, in addition to the rarity and heterogeneity of the disease, high-quality data are lacking and epNECs remain poorly understood. While certain prognostic factors have been identified, many of these are controversial and are yet to be validated. This review summarizes existing evidence on survival, key prognostic factors, and the impact on patient quality of life in this understudied group of malignancies. Understanding survival patterns and key prognostic features of this aggressive group of malignancies is crucial to inform clinical decision-making and shape the design of future clinical trials. This review emphasizes a need for multicenter involvement to conduct clinical trials to develop more effective front-line therapies. Additionally, the current limited treatment landscape highlights the need to shift to a personalized, biomarker-driven treatment approach (e.g. DLL3), with a call for comprehensive, standardized biomarker testing for all epNECs.