P56.01 Semiquantitative Assessment of Tumor Spread Through Air Spaces in a Historic Cohort of Lung Adenocarcinomas Following Open Surgical Resection

Abstract

“Aerogenous” spread of lung cancer has been noted since 1980. The equivalent "spread through air spaces (STAS)” was introduced in the 2015 World Health Organization (WHO) Classification of Lung Tumors as a new concept of invasion. Previous studies have shown that STAS occurred in 34-51.4% of resected lung tumors (across all stages) and is associated with poor outcomes. However, some evidence suggests that STAS represents ex vivo artifact. For example, retrieval of the specimen through a small port during video-assisted thoracic surgery (VATS) could detach tumor cell clusters via mechanical force. This study examines the STAS status of lung cancer before VATS was widely used. Invasive lung adenocarcinomas surgically resected via thoracotomy at our institution between 1990 and 1992 were analyzed semi-quantitatively as "no STAS", "low STAS” (1–4 single cells or clusters), or "high STAS” (≥5 single cells or clusters) on hematoxylin and eosin stained slides. The distance between the farthest STAS focus lying within the alveolar space and the edge of the main tumor (Maximal Spread Distance, MSD) was measured. We excluded cases with multiple foci of tumor, preoperative radiation and/or chemotherapy, positive surgical margins, or distant metastasis from the study population. Stage-matched invasive lung adenocarcinomas resected by VATS in 2020 were retrieved with the same criteria and compared. A chi-squared test or Fisher's exact test was performed on Prism 5 (GraphPad) to determine the impact of clinicopathologic parameters on STAS. P values were considered statistically significant at less than 0.05. Between 1990 and 1992, 56 lung resections met criteria for inclusion. The mean age of the study cohort was 64.4 years (range 37–83), and 51.8% were male. Thirty-two cases (57.1%) underwent lobectomy, 21 cases (37.5%) sublobar resection, 3 cases (5.4%) pneumonectomy. The mean size of tumor was 3.0 cm (range 0.8 - 10 cm). Among the histologic subtypes, 23 cases (41.1%) were acinar predominant, followed by solid (26.8%), papillary (21.4%), micropapillary (8.9%) and lepidic (1.8%) subtypes. Of these, we found STAS present in 42/56 cases (75%) and no STAS in the remaining 14 cases (25%). In the group with STAS, 10 cases (17.9%) had low STAS and 32 cases (57.1%) had high STAS. The MSD was greater than 0.5 cm in 35 cases (83.3% of STAS cases). There were no statistically significant associations between STAS and gender, age, operation, predominant subtypes of adenocarcinoma, tumor size, pleural invasion, lymphovascular invasion, or tumor stage. In comparison, STAS was identified in 54 of 88 cases resected in 2020 (61.4%). The incidence of STAS was higher in 1990-92 than in 2020 (P= 0.045). The lower rates of STAS in contemporary cohorts may reflect shifts in lung cancer biology and disease management over the last 30 years. These findings suggest that VATS does not contribute significantly to generation of artifactual tumor STAS.