Tumor Spread through Air Spaces is an Important Pattern of Invasion and Impacts the Frequency and Location of Recurrences after Limited Resection for Small Stage I Lung Adenocarcinomas

Abstract

Introduction Tumor invasion in lung adenocarcinoma is defined as infiltration of stroma, blood vessels, or pleura. Based on observation of tumor spread through air spaces (STAS), we considered whether this could represent new patterns of invasion and investigated whether it correlated with locoregional versus distant recurrence according to limited resection versus lobectomy. Methods We reviewed resected small (≤2 cm) stage I lung adenocarcinomas (n=411; 1995–2006). Tumor STAS was defined as tumor cells—micropapillary structures, solid nests, or single cells—spreading within air spaces in the lung parenchyma beyond the edge of the main tumor. Competing risks methods were used to estimate risk of disease recurrence and its associations with clinicopathological risk factors. Results STAS was observed in 155 cases (38%). In the limited resection group (n=120), the risk of any recurrence was significantly higher in patients with STAS-positive tumors than that of patients with STAS-negative tumors (5-year cumulative incidence of recurrence [CIR], 42.6% vs. 10.9%; P<0.001); the presence of STAS correlated with higher risk of distant (P=0.035) and locoregional recurrence (P=0.001). However, in the lobectomy group (n=291), presence of STAS was not associated with either any (P=0.50) or distant recurrence (P=0.76). In a multivariate analysis, presence of tumor STAS remained independently associated with the risk of developing recurrence (hazard ratio, 3.08; P=0.014). Conclusion Presence of STAS is a significant risk factor of recurrence in small lung adenocarcinomas treated with limited resection. These findings support our proposal that STAS should formally be recognized as a pattern of invasion in lung adenocarcinoma.

How to deal with subcentimeter lung cancer: a moving target!

“…Most probably, with the latter histological diagnoses a lobectomy is still the most appropriate treatment to obtain good long-term results. A newly recognized pattern is spread through air spaces (STAS) where tumor deposits are present in lung parenchyma around the primary tumor without direct connection (8). As can be expected, a higher rate of recurrences has been described with this particular growth pattern (8).…”

Surgical pathology of early stage non-small cell lung carcinoma

“…The authors also raise the possibility that in patients with small percentages of micropapillary tumor (5%) who do poorly may progress because of "micropapillary STAS". Of potential treatment significance, patients with STAS had a poorer prognosis only when they underwent limited resection, but not in those who underwent lobectomy, suggesting a role for lobectomy even in small lesions (39).…”

What is spread through air space?

“…Although several studies found presence of STAS to be a worse prognostic factor, its influence in staging was unknown. Dai et al (6) showed that patients with stage I adenocarcinoma <2-3 cm and the presence of STAS, which was based on the definition by Kadota et al (2), had prognosis similar to that of patients with stage IB adenocarcinoma; therefore, STAS may possibly change the pathologic stage of a tumor. The concept of STAS has also been applied to squamous cell carcinoma of the lung.…”

“…Interestingly, the connection of a tumor island to the main tumor was demonstrated by three-dimensional reconstruction analysis. Kadota et al (2) reported that tumor spread through air spaces (STAS), defined as the presence of tumor cells that goes beyond the edge of the main tumor to within at least the first alveolar layer in the lung parenchyma, was a significant risk factor for recurrence of small (≤2 cm) lung adenocarcinoma in patients who underwent limited resection. We showed that semiquantitative assessment was a useful prognostic factor in patients with small (≤2 cm) lung adenocarcinoma.…”