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Introduction Gender difference may affect lung neuroendocrine tumors (L-NET) onset, progression and outcomes as emerged in other cancers. This study aims to analyse gender difference in L-NET to identify potential prognostic factors, to improve patient follow-up and therapeutic strategies. Methods Patients (pt) with histologically confirmed L-NEN diagnosis referred to the ENETS CoE of the Endocrinology Unit, Federico II University of Naples, from 2013 to 2023 were retrospectively evaluated. Results Among 48 pt with L-NEN, 38 (79,2%) with sporadic L-NET were enrolled: 22 typical (57,9%) and 16 atypical (42,1%) carcinoids, 22 (57,9%) female and 16 (42,1%) male, mean age at diagnosis 57,3 years (range 16-84). Median follow up was 70,5 months (range 12-305). No statistically difference resulted regardig smoking habit, body mass index (BMI), primary site (left/right and central/peripheral) and histological characteristics, between cohorts. Metastasis at diagnosis were found in 20 pt (52,3%), 10 female (10%%), 10 male (10%) (p:0,20). Progressive disease (PD) was observed in 14 (36,8%) pt, male sex developed PD more frequently 9/14 (64,3%) than female 5 (35,7%), p: 0.05. Male sex seemed to show more frequently bone metastasis without reaching statistically difference, 7male/10 (70%), p: 0.06. Among 9 deaths (23,7%), 7 (77,8%) were men and 7 died for PD, p<0,03. Male had a poorer prognosis than female regarding progression free survival (p: 0,04) and overall survival (p:0,001), also when sub-groups of pt metastatic at diagnosis were compared (p: 0,02 and p:0,02). Conclusions This study showed a worse prognosis in male than female with L-NET, despite similar clinical features, tumour type, stage and treatment, with regard to PFS, OS and metastatic spread. These findings may suggest a closer follow up in men, with potential positive impact on outcomes.

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