Spread Through Air Spaces in Stage I Pulmonary Large Cell Neuroendocrine Carcinoma

BACKGROUND Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents an exceptionally aggressive and infrequent variant within the realm of non-small cell lung cancer, necessitating surgical intervention as the primary therapeutic approach. However, the postoperative management strategy for early-stage patients continues to be a subject of intense debate and uncertainty. METHODS Retrospective analysis was conducted on a cohort of patients diagnosed with LCNEC who underwent surgical resection at Shanghai Pulmonary Hospital between July 2018 and June 2022. Comprehensive assessments, encompassing univariate and multivariate analyses, were performed to evaluate the prognostic significance of these indicators in terms of patient clinical profiles, OS, and DFS. RESULTS A comprehensive screening effort identified a total of 171 patients with LCNEC, with 70 stage I patients meeting the criteria for inclusion in the final cohort. 11 patients (15.7%) presented with combined LCNEC, while 59 patients (84.3%) exhibited pure LCNEC. Both univariate and multivariate analyses unveiled that Spread through air spaces (STAS) status emerged as an independent prognostic determinant for both DFS and overall OS (p = 0.003, p = 0.013, respectively), while histological subtype independently predicted OS (p = 0.011). Subgroup survival analyses further underscored that the advantageous effects of postoperative chemotherapy were significantly pronounced exclusively among STAS-positive patients, showcasing a statistically significant enhancement in DFS and OS (p = 0.047 and p = 0.018, respectively). CONCLUSIONS STAS may serve as an adverse prognostic factor in stage I LCNEC patients, potentially offering guidance for postoperative chemotherapy decisions.