Pancreatic Neuroendocrine Neoplasms: Does Sex Matter?

Genetic and molecular disparities between men and women have a role in the differing incidence, pathophysiology, clinical signs, and treatment outcome of several cancers. Sex differences in cancer incidence are attributed to regulation at the genetic/molecular level and to sex hormones that in turn modulate gene expression in various cancers. Sex differences in the incidence of cancer, its aggressiveness, and the disease prognosis have been reported for several types of cancer but little is known for pancreatic neuroendocrine neoplasms (PNENs). The aim of this Opinion article is to provide an overview of sex differences in PNENs in terms of epidemiology, pathophysiology, treatment responses, prognosis, and survival. This overview might allow better tailoring of the management of PNENs. Pancreatic neuroendocrine neoplasms (PNENs) are rare neoplasms with malignant potential whose incidence is on the rise; their clinical behavior mostly depends on the grade and the stage of the tumor.In addition, recent studies have emphasized a sex difference in PNENs in terms of clinical behavior. Male patients with PNENs have a worse prognosis, a greater risk of disease recurrence after curative surgery, and a higher incidence of complications than females. Conversely, female patients with PNENs have a longer survival and a better response to locoregional treatment of liver metastases than males. No significant sex differences have yet been demonstrated with regard to the response to treatment with somatostatin analogs, chemotherapy, peptide receptor radionuclide therapy, or molecularly targeted therapies. Considering the close relationship between sex and clinical behavior in PNENs, sex-driven management of PNENs appears to be needed.