Epidemiology of Undifferentiated Carcinomas

SIMPLE SUMMARY: When compared microscopically to normal cells, cancer cells are graded on a continuum from well differentiated to undifferentiated, meaning that well differentiated cancer cells look similar to normal cells and undifferentiated ones look very different. Patient survival outcomes typically decrease along this continuum. However, some cancer cells are so undifferentiated that it is not certain from which cell type they arose from. It is not known if these patients have worse outcomes compared to undifferentiated cancers where the cell type origin can be determined. In this study, we show that patient outcomes from undifferentiated cancers depend on the site, and generally, outcomes are worse compared to undifferentiated cancers with a discernible cell type, but there are some notable exceptions. This work illustrates that tumor site has significant impacts on patient survival even when accounting for multiple demographic, clinical, and histological factors. ABSTRACT: Undifferentiated carcinomas are rare cancers that lack differentiation, such that they cannot be classified into any conventional histological subtype. These cancers are uniquely codified and are contrasted to carcinomas with an ascertained histology that are grade classified as poorly differentiated, undifferentiated, or anaplastic. Given their rarity, there are no standardized overviews of undifferentiated carcinomas in the literature, and it is unknown if their classification indicates a unique prognosis profile. In this study, we summarize the clinicodemographic and mortality outcomes of undifferentiated carcinomas in twelve primary sites and for unknown primaries, comprising 92.8% of all undifferentiated carcinomas diagnosed from 1975–2017 in the Surveillance, Epidemiology, and End Results Program (SEER). Incidence has decreased to 4 per 1 million cancer diagnoses since 1980. Relative to the most common undifferentiated cancers with a defined histology, undifferentiated carcinomas have overall worse prognosis, except in nasopharyngeal and salivary gland cancers (hazard ratio (HR) 0.7–1.3). After correction for age, sex, race, detection stage, and treatment (surgery, chemotherapy, and radiotherapy), the mortality HR averages 1.3–1.4 for these cancers relative to histologically ascertainable undifferentiated cancers. However, there is a wide variance depending on site, signifying that survival outcomes for undifferentiated carcinomas depend on factors related to site tumor biology.