Hormone secretion predicts poor prognosis in lung neuroendocrine neoplasms

Ectopic hormone secretion from neuroendocrine neoplasms in the lung (lung-NENs) is rare and poorly explored. Emerging evidence indicates that hormone-secreting NENs carry a worse prognosis. We hypothesised that ectopic hormone production and secretion in lung-NENs is a negative prognostic marker. A retrospective cohort of 167 patients with lung-NENs (121 females, median age: 68 (min-max: 15-85) years), excluding small cell lung cancer, was analysed for clinical and biochemical data and outcome. Tumour tissue was evaluated for serotonin and calcitonin expression. Among 127 patients with hormone measurements, 52 had increased levels, with 5-hydroxyindoleacetic acid (5-HIAA) predominating (n = 38), followed by calcitonin (n = 20). There was no correlation between serotonin expression in tumour tissue and elevated levels of 5-HIAA, while high calcitonin levels were strongly correlated with calcitonin expression in tumour samples (OR: 21.86, P = 0.002). Furthermore, diffuse calcitonin staining was associated with a shorter overall survival (OS) (P = 0.036). Hormone-secreting tumours had a significantly shorter OS than non-secreting tumours (62 vs 124 months, P = 0.024), and multiple hormone secretion further worsened survival (33 vs 69 vs 124 months, P = 0.002). In multivariate analysis, multiple hormone secretion remained an independent negative prognostic factor (P = 0.042). In conclusion, hormone secretion in lung-NENs is associated with a shorter OS, particularly in patients with multiple hormone secretion. Diffuse calcitonin expression in tumour tissue is an additional negative prognostic marker. We recommend routine hormone testing at baseline and at disease progression in metastatic lung-NEN patients and suggest a more intensified therapeutic strategy in cases with detectable hormone secretion.