Significance of Spread Through Air Spaces in Resected Pathological Stage I Lung Adenocarcinoma

Gouji Toyokawa, Yuichi Yamada, Tetsuzo Tagawa, Yuka Kozuma, Taichi Matsubara, Naoki Haratake, Shinkichi Takamori, Takaki Akamine, Yoshinao Oda, Yoshihiko Maehara

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)


Background: “Spread through air spaces” (STAS) is a recently described invasive pattern of lung cancer that spreads within air spaces beyond the edge of the main tumor. In the current study, we investigated the significance of STAS in patients with pathologic stage I adenocarcinoma. Methods: We assessed STAS in a total of 276 patients with resected pathologic stage I adenocarcinoma. STAS was classified as either no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS) using a 20x objective and a 10x ocular lens. We evaluated the association between STAS and the clinicopathologic characteristics and postoperative survivals. Results: Among 276 patients, 123 (44.6%), 48 (17.4%), and 105 (38.0%) were classified as having no, low, and high STAS, respectively. The positivity for STAS was significantly associated with larger radiologic tumor diameter (p = 0.008), higher consolidation/tumor ratio (p < 0.001), higher maximum standard uptake value (p < 0.001), pathologically larger tumor size (p = 0.004), pleural invasion (p = 0.027), and histologically invasive type (p < 0.001); whereas STAS was not significantly associated with epidermal growth factor receptor mutations or programmed death ligand-1 expression (p = 0.129 and p = 0.872, respectively). Patients with STAS had significantly shorter recurrence-free and overall survival than patients without STAS (p < 0.001 and p = 0.002, respectively). According to a multivariate analysis, positivity for STAS remained an independent prognostic factor for both recurrence-free survival and overall survival. Conclusions: Spread through air spaces was associated with clinicopathologically invasive features and was predictive of worse survival.

Original languageEnglish
Pages (from-to)1655-1663
Number of pages9
JournalAnnals of Thoracic Surgery
Issue number6
Publication statusPublished - Jun 2018

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine


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