Solid Nodule Appearance as a Predictor of Tumor Spread Through Air Spaces in Patients with Lung Adenocarcinoma: A Propensity Score Matching Study

Qingpeng Zeng,1 Bingzhi Wang,2 Jiagen Li,1 Jun Zhao,1 Yousheng Mao,1 Yushun Gao,1 Qi Xue,1 Shugeng Gao,1 Nan Sun,1 Jie He1 1Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Jie HeDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Beijing 100021, People’s Republic of ChinaEmail prof.jiehe@gmail.comObjective: Spread through air spaces (STAS) has been reported to be an invasive histological pattern with poor prognosis in lung cancer; however, little is known about its intrinsic risk factors. This work analyzed the correlation between pathological and radiological features and STAS in resected lung adenocarcinomas.Patients and Methods: We retrospectively reviewed 1821 consecutive surgically treated patients with histologically diagnosed lung adenocarcinoma (174 positive for STAS and 1647 negative for STAS) from December 2017 to November 2018 at our institution. Propensity score matching identified 170 well-balanced pairs of patients. The correlations between pathological and radiological features and the presence of STAS were analyzed.Results: Before propensity matching, the incidence rate of STAS was 9.6% in all patients. In matched cohorts, multivariate analysis showed that the presence of STAS was significantly correlated with pure solid nodules (SNs) (p = 0.001) and solid/micropapillary patterns (SMPs) (p = 0.002). The odds ratio for STAS in SN-positive and SMP-positive adenocarcinoma against that in SN-negative and SMP-negative adenocarcinoma was 10.922 (95% confidence interval, 5.826– 20.475; p < 0.001). Tumor differentiation, visceral pleural invasion (VPI), lymphovascular invasion (LVI), invasive adenocarcinoma, and non-lepidic subtype were significantly associated with STAS in the univariate analysis (p < 0.05); however, the differences failed to reach a significant level in the multivariate analysis.Conclusion: We found that STAS was significantly correlated with several invasive clinicopathological patterns. The presence of SNs and SMPs were revealed as independent predictors for STAS, which could offer clinicians clues to identify STAS-positive adenocarcinoma.Keywords: lung adenocarcinoma, spread through air spaces, solid pulmonary nodule