Background/Objectives: Metabolic alterations, including dyslipidemia, may influence tumor biology and treatment outcomes in neuroendocrine tumors. However, the clinical relevance of dyslipidemia and lipid-lowering therapy in bronchopulmonary neuroendocrine tumors (BP-NETs) treated with somatostatin analogues (SSAs) remains poorly defined. This translational proof-of-concept study evaluated progression-free survival (PFS) in patients with advanced BP-NETs receiving SSAs according to dyslipidemia and statin therapy and explored the effects of statin-SSA combination treatment in vitro. Methods: We retrospectively analyzed 24 patients with advanced well-differentiated BP-NETs treated with SSAs as first-line therapy. Fourteen patients (58.3%) had dyslipidemia, and 11 of them were receiving statins. In parallel, NCI-H727 cells were treated with atorvastatin (10 µM), lanreotide (5 or 10 µM), or their combination for 48–72 h. Cell viability, proliferation, cell death, apoptosis, DNA damage, and ATP production were assessed. Results: Median PFS was 22.5 months overall. A trend toward longer PFS was observed in non-dyslipidemic vs. dyslipidemic patients (70 vs. 36 months, p = 0.08). Among dyslipidemic patients, statin therapy was associated with a non-significant trend toward longer PFS compared with no statin therapy (36 vs. 18 months, p = 0.30). In vitro, combined atorvastatin–lanreotide treatment reduced cell viability and proliferation, increased cell death, enhanced cleaved caspase-3 and p-γH2AX expression, and reduced ATP production. Conclusions: These findings support the potential relevance of lipid metabolism modulation as an adjunct strategy in advanced BP-NETs while highlighting the need for larger prospective studies and dedicated biochemical investigation of the underlying lipid-related pathways.

Background/Objectives: Metabolic alterations, including dyslipidemia, are increasingly recognized in patients with neuroendocrine tumors and may influence tumor biology and treatment outcomes. However, the clinical relevance of dyslipidemia and the potential impact of lipid-lowering therapies in bronchopulmonary neuroendocrine tumors (BP-NETs) treated with somatostatin analogues (SSAs) remain poorly defined. This study aimed to evaluate the progression-free survival (PFS) in patients with advanced BP-NETs receiving SSAs according to dyslipidemia as well as statin therapy. In addition, an exploratory in vitro analysis was performed to assess the combined biological effect of statins and SSAs. Methods: This study investigated the combined effects of atorvastatin and lanreotide therapy both in vitro and in a clinical setting. In NCI-H727 cells, we assessed cell viability, proliferation, apoptosis, DNA damage, and metabolic activity following single and combined treatments. Concurrently, we retrospectively evaluated the impact of dyslipidemia and statin therapy on progression-free survival (PFS) in patients with advanced BP-NETs receiving SSAs. Results: Combined treatment resulted in reduced cell viability, proliferation, and ATP production, alongside increased apoptosis and DNA damage, and was associated with impaired cellular energy metabolism compared with lanreotide alone and control conditions. In the clinical analysis, dyslipidemia was associated with shorter progression-free survival (PFS), whereas atorvastatin therapy in dyslipidemic patients showed a positive trend toward improved PFS. Conclusions: These findings support the potential relevance of lipid metabolism modulation as an adjunct strategy in advanced BP-NETs, warranting further validation in larger prospective studies and encouraging additional biochemical investigation of the underlying pathways.