Impact of sex on treatment decisions and outcome in patients with neuroendocrine neoplasms

Sex differences affect the management of several diseases in both male and female patients. However, the influence of sex on neuroendocrine neoplasms (NENs) has been scarcely investigated. Thus, this study aimed to compare tumor characteristics, treatment decisions, and overall survival in patients with NENs, stratified by sex. The retrospective analysis of the SwissNET cohort covered NENs of gastroenteropancreatic, pulmonary, or unknown origin from July 2014 to September 2022. The analysis included 1985 patients (46% female and 54% male). No significant difference in tumor grading was found between male and female patients. However, male patients presented with higher staging at time of diagnosis and with more lymph node and bone metastases. Surgery was performed more often in female compared to male patients (73.4% vs 68.7%, P = 0.023). Male patients received peptide receptor nuclide therapy (PRRT) earlier than female patients (7.8 months vs 13.1 months from time of diagnosis, P = 0.003). The median overall survival was significantly shorter for male compared to female patients (male: 18 years, female: not reached, P < 0.001, hazard ratio (HR) 1.55 (1.19–2.01), P = 0.001). Multivariable analyses revealed advanced age (HR 1.02 (1.01–1.04)), cancer of unknown origin (HR 2.01 (1.09–3.70)), higher grading (G3: HR 6.74 (4.22–10.76)), having metastases at the time of diagnosis (HR 2.11 (1.47–3.02)), and surgical treatment (HR 0.67 (0.48–0.93)) as independent predictors for overall survival. In conclusion, male sex was associated with worse outcome in NEN patients, likely due to more advanced tumor stage at the time of diagnosis. Further investigations are required to understand the underlying mechanisms of these sex differences.