The More Extensive the Spread through Air Spaces, the Worse the Prognosis Is: Semi-Quantitative Evaluation of Spread through Air Spaces in Pulmonary Adenocarcinomas

Abstract

Introduction: The extent of spread through air spaces (STAS) is less investigated among patients with lung adenocarcinoma who underwent sublobar resection. Therefore, we aimed to evaluate the extent of STAS semi-quantitatively, to assess its prognostic impact on overall survival (OS) and recurrence-free survival (RFS), and to investigate the reproducibility of this assessment.

Methods: The number of tumour cell clusters and single tumour cells within air spaces was recorded in three different most prominent areas (200x field of view). The extent of STAS was categorized into three groups, and the presence of free tumour cluster (FTC) was recorded.

Results: Sixty-one patients were included. Recurrence was more frequent with higher grade (p = 0.003), presence of lymphovascular invasion (p = 0.027), and presence of STAS of any extent (p = 0.007). In multivariate analysis, presence of FTC (HR: 5.89; 95% CI: 1.63-21.26; p = 0.005) and more pronounced STAS (HR: 7.46; 95% CI: 1.60-34.6; p = 0.01) had adverse impact on OS and RFS, respectively. Concerning reproducibility, excellent agreement was found among STAS parameters (ICC range: 0.92-0.94).

Discussion: More extensive STAS is an unfavourable prognostic factor in adenocarcinomas treated with sublobar resection. As the evaluation of extent of STAS is reproducible, further investigation is required to gather more evidence.

Keywords: Free tumour cluster; Pulmonary adenocarcinoma; Semi-quantitative analysis; Spread through air spaces; Sublobar resection.

Fig. 1

Histological patterns of non-mucinous lung adenocarcinoma (haematoxylin-eosin, ×10). a Lepidic. b Acinar. c Papillary. d Solid. e Micropapillary. f Cribriform.

Fig. 2

Spectrum and mimickers of STAS. a Single neoplastic cell cluster in the peritumoral area. b Several neoplastic cell clusters in the peritumoral alveoli. c Example for artificial tumour disintegration (STAKS).

Fig. 3

a Kaplan-Meier analysis of “low STAS” and “high STAS” scheme. Significant differences were found between the OS estimates of STAS− versus “high STAS” tumours (p < 0.001) and between of STAS− versus “low STAS” tumours (p = 0.04). b Significant differences were detected between the RFS estimates of STAS− versus “high STAS” tumours (p < 0.001) and “high STAS” versus “low STAS” tumours (p = 0.031). c Kaplan-Meier analysis of STAS with or without FTC. Significant differences were found between the OS estimates of STAS− versus STAS+/FTC+ tumours (p < 0.001), between of STAS− versus STAS+/FTC− tumours (p < 0.001) and between of STAS+/FTC− versus STAS+/FTC+ tumours (p = 0.025). 3-Y-OS, 3-year OS; 3-Y-RFS, 3-year RFS.