Clinical Importance of Grading Tumor Spread through Air Spaces in Early-Stage Small-Lung Adenocarcinoma

Simple Summary: This study explored how lung cancer spreads through air spaces in small tumors (up to 2 cm) and its impact on patient outcomes. Focusing on small-size and early-stage lung adenocarcinomas, the researchers analyzed medical records of patients treated between 2012 and 2022. We measured the distance of floating cancer cells spread from the main tumor through alveolar spaces and categorized patients based on whether this spread was present and its extent. Interestingly, while overall survival rates were similar across groups, patients with more extensive spread (2 mm or more) experienced a higher chance of cancer recurrence even in this very early cancer. This suggests that understanding the extent of spread through air spaces is crucial in predicting cancer recurrence in small lung tumors. Further research with a larger group of patients is needed to confirm these risk factors and improve treatment strategies. This study aimed to identify the clinical manifestation and implications according to the grading of tumor spread through air spaces in early-stage small (<= 2 cm) pathological stage I non-mucinous lung adenocarcinomas. Medical records of patients with pathological stage I tumors sized <= 2 cm were retrospectively reviewed and analyzed. The furthest distance of the spread through air spaces from the tumor margin was measured on a standard-length scale (mm). Enrolled patients were categorized into spread through air spaces (STAS) (-) and STAS (+), and STAS (+) was subdivided according to its furthest distance as follows: STAS (+)-L (<2 mm) and STAS (+)-H (>= 2 mm). Risk factors for STAS (+) included papillary predominant subtype (p = 0.027), presence of micropapillary patterns (p < 0.001), and EGFR (p = 0.039). The overall survival of the three groups did not differ significantly (p = 0.565). The recurrence-free survival of STAS (+)-H groups was significantly lower than those of STAS (-) and STAS (+)-L (p < 0.001 and p = 0.039, respectively). A number of alveolar spaces were definite risk factors for STAS (+)-H groups (p < 0.001), and male gender could be one (p = 0.054). In the patient group with small (<= 2 cm) pathological stage I lung adenocarcinomas, the presence of STAS >= 2 mm was related to significantly lower recurrence-free survival. For identifying definite risk factors for the presence of farther STAS, more precise analysis from a larger study population should be undertaken.