Prognostic heterogeneity of lung cancer associated with cystic airspaces and identification of novel imaging subtypes: a multi-center cohort study

Background: Lung cancer associated with cystic airspaces (LCCA), a rare subtype of non-small cell lung cancer (NSCLC), presents with cystic structures that challenge diagnosis and staging. Long-term prognostic features and risk factors for LCCA remain unclear. Methods: This multicenter study included 2,693 patients (415 LCCA, 2,278 non-LCCA) treated with thoracoscopic surgery at three institutions from January 2016 to December 2017. Propensity score matching was applied to balance baseline characteristics. Kaplan-Meier and Cox regression analysis were used to compare 5-year overall survival (OS) between LCCA and non-LCCA groups. We innovatively classified LCCA based on radiological features and explored the association between LCCA subtype imaging characteristics and OS. Results: The 5-year OS of LCCA group was significantly worse than that of non-LCCA group (70.0% vs. 90.5%, P = 0.03). Radiological subtyping of LCCA showed a significantly prognostic gradient in 5-year OS: pure ground-glass opacity (pGGO, 83.3%), mixed ground-glass opacity (mGGO, 71.4%), and solid nodule (SN, 50.8%), with the SN subgroup exhibiting the worst prognosis (P<0.01). In the SN subgroup, irregular cyst morphology (HR: 1.65, P = 0.02), cyst number (HR: 1.18, P<0.01), wall nodule diameter (HR: 23.09, P<0.01), and differentiation grade (HR: 3.25, P<0.01) were independent predictors of worse prognosis. Cystic lesion diameter in CT was larger than pathological diameter across all LCCA subtypes (P<0.01). Conclusions: LCCA has a significantly worse long-term prognosis than non-LCCA. LCCA with SN component identified as a high-risk subtype driven by distinct radiological and pathological features. The discrepancy between CT and pathological tumor diameters suggests that current T-staging may lead to potential T-stage overestimation in LCCA. A specialized staging criteria for LCCA need to be further explored.