Gender-related differences in patients with carcinoid syndrome: new insights from an Italian multicenter cohort study

Background: The incidence of neuroendocrine neoplasm (NEN) and related carcinoid syndrome (CaS) has increased markedly in recent decades, and women appear to be more at risk than men. As per other tumors, gender may be relevant in influencing the clinical and prognostic characteristics of NEN-associated CS. However, specific data on carcinoid syndrome (CaS) are still lacking. Purpose: To evaluate gender differences in clinical presentation and outcome of CaS. Methods: Retrospective analysis of 144 CaS patients from 20 Italian high-volume centers was conducted. Clinical presentation, tumor characteristics, therapies, and outcomes (progression-free survival, PFS, overall survival, OS) were correlated to gender. Results: Ninety (62.5%) CaS patients were male. There was no gender difference in the site of primary tumor, tumor grade and clinical stage, as well as in treatments. Men were more frequently smokers (37.2%) and alcohol drinkers (17.8%) than women (9.5%, p= 0.002, and 3.7%, p= 0.004, respectively). Concerning clinical presentation, women showed higher median number of symptoms (p= 0.0007), more frequent abdominal pain, tachycardia, and psychiatric disorders than men (53.3% vs 70.4%, p= 0.044; 6.7% vs 31.5%, p= 0.001; 50.9% vs. 26.7%, p= 0.003, respectively). Lymph node metastases at diagnosis were more frequent in men than in women (80% vs 64.8%; p= 0.04), but no differences in terms of PFS (p= 0.51) and OS (p= 0.64) were found between gender. Conclusions: In this Italian cohort, CaS was slightly more frequent in males than females. Gender-related differences emerged in the clinical presentation of CaS, as well as gender-specific risk factors for CaS development. A gender-driven clinical management of these patients should be advisable.