Abstract
Background: The role of gender has gained attention in oncology. In the setting of lung neuroendocrine tumors (L-NETs), the existence of differences between male and females has been suggested, but no clear-cut data are available. We aimed to provide a critical analysis of the existing literature regarding sex roles in L-NETs. Methods: We performed an extensive search of the available literature to provide a critical narrative review focused on key topics such as epidemiology, histopathological and molecular features, functioning syndromes, prognosis, and response/toxicity to treatments in L-NETs according to sex. Results: Female patients are more likely to have an L-NET than males. The reasons underlying these gender differences are still unclear; a biologic mechanism for the sex difference is possible, through a role of hormones in regulating gene expression and promoting neuroendocrine cell proliferation. A difference in immunohistochemical biomarkers has been found; thyroid transcription factor-1 (TTF-1) expression appears to be associated with female gender; at the molecular level, in the majority of studies, L-NET mutational profile is not stratified for sex. In terms of prognosis, a correlation between male gender and a more aggressive disease has been found. Patient’s gender has been recognized as a key modulator in the response/resistance to anticancer treatments; however, for L-NETs, the available data regarding the activity of different treatments and their toxicities are scarce, as in clinical trials designed for L-NETs, a stratified evaluation of drugs’ activity according to patients’ sex is largely missing. Conclusions: There is emerging evidence suggesting a gender role in L-NETs; however, further studies are needed to better understand the pathogenesis of these tumors and to plan tailored treatments. Graphical Abstract: for Graphical Abstract, see https://doi.org/10.1159/000546081.
Plain Language Summary
In the last decades, increasing relevance has been recognized for gender as a key determinant in human pathologies and cancer, paving the way for the Gender Medicine field. The role of sex has emerged as fundamental in oncology, with clear differences in cancer epidemiology, biology of the tumors, clinical presentation, and response to treatments. L-NETs account for approximately 30% of well-differentiated NET and are characterized by extreme heterogeneity in terms of biologic aggressiveness and clinical course. A role has been reported for gender, suggesting the existence of differences between males and females with these tumors, but a critical review of this issue is missing. Our review aimed to fill this gap by exploring the available data about the role of sex in L-NETs, providing a detailed analysis of the current literature and a critical overview. We believe our findings could serve as a valuable resource for both researchers and clinicians.
