Tumor Spread Through Air Spaces Is an Independent Predictor of Recurrence-free Survival in Patients With Resected Lung Squamous Cell Carcinoma

Abstract

Tumor spread through air spaces (STAS) is a newly recognized pattern of invasion in lung adenocarcinoma. However, clinical significance of STAS has not yet been characterized in lung squamous cell carcinoma. In this study, we investigated whether STAS could determine clinical outcome in Japanese patients with lung squamous cell carcinoma. We reviewed tumor slides from surgically resected lung squamous cell carcinomas (n=216). STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. Tumors were evaluated for histologic subtypes, tumor budding, and nuclear diameter. Recurrence-free survival (RFS) was analyzed using the log-rank test and the Cox proportional hazards model. Tumor STAS was observed in 87 patients (40%), increasing incidence with lymph node metastasis (P=0.037), higher pathologic stage (P=0.026), and lymphatic invasion (P=0.033). All cases with STAS showed a solid nest pattern. The 5-year RFS for patients with STAS was significantly lower than it was for patients without STAS in all patients (P=0.001) and in stage I patients (n=134; P=0.041). On multivariate analysis, STAS was an independent prognostic factor of a worse RFS (hazard ratio=1.61; P=0.023). Patients with STAS had a significantly increased risk of developing locoregional and distant recurrences (P=0.012 and 0.001, respectively). We found that tumor STAS was an independent predictor of RFS in patients with resected lung squamous cell carcinoma, and it was associated with aggressive tumor behavior.

Spread through air spaces (STAS): a comprehensive update

“…As demonstrated in ADC (2) the extent of STAS was not relevant for prognosis (12). The prognostic impact of STAS in SCC was most recently confirmed in a series of 2016 cases from Japan (17). Thus, beyond budding and cell nest size which has previously been identified as prognostically relevant morphological parameters in SCC (18)(19)(20)(21), STAS seems to be another morphological feature to allow for a better prognostic stratification of SCC and potentially the establishment of a clinically meaningful grading system in the near future.…”

Spread through air spaces (STAS): prognostic impact of a semi-quantitative assessment

“…As demonstrated in ADC (2) the extent of STAS was not relevant for prognosis (12). The prognostic impact of STAS in SCC was most recently confirmed in a series of 2016 cases from Japan (15). Thus, beyond budding and cell nest size which have previously been identified as prognostically relevant morphological parameters in SCC (16)(17)(18)(19).…”

Tumor spread through air space, the clinical implications for T factor and effects on the disease recurrence and prognosis

“…STAS is recognized in approximately 30-50% of lung adenocarcinomas (5,6). Furthermore, recent publications have reported that STAS coexistence in squamous cell carcinoma was also associated with poor clinical outcomes after surgery (7,8).…”