The Prognostic Significance of SMARCA4 Deficiency in Early-Stage Pulmonary Large Cell Carcinoma

Large cell carcinoma (LCC) is a rare subtype of non-small cell lung cancer (NSCLC) characterized by high prevalence of SMARCA4 deficiency and aggressive clinical behavior. However, despite these clinical parameters, the benefits of adjuvant therapy in early-stage LCC remain controversial.

This study included all LCC patients who underwent surgical resection at Shanghai Pulmonary Hospital between June 2017 and April 2023. Oncological outcomes were assessed through univariate and multivariate Cox regression analyses.

Of the 157 LCC patients initially screened, 98 met the criteria for inclusion in the final cohort. SMARCA4 deficiency was present in 28 patients (28.6%), and spread through air spaces (STAS) was observed in 20 patients (20.4%). Multivariate Cox regression identified SMARCA4 deficiency (hazard ratio [HR] 2.19; P = 0.042) and STAS-positive status (HR 4.00; P < 0.001) as independent prognostic factors for disease-free survival (DFS). Subgroup survival analyses of early-stage LCC further revealed that adjuvant chemotherapy significantly improved DFS (P = 0.049) and overall survival (OS) (P = 0.088) in patients with SMARCA4 deficiency. In contrast, among SMARCA4-intact patients, DFS and OS were comparable between the treatment and non-treatment groups (P = 0.718 and P = 0.462, respectively).

SMARCA4 deficiency and STAS-positive status are independent predictors of poor prognosis in LCC patients. Moreover, SMARCA4 deficiency may serve as a valuable marker for guiding adjuvant chemotherapy in early-stage LCC.