The prognostic impact of extra-alveolar invasion in lung adenocarcinoma

Recent studies in lung cancer pathology have focused on histological patterns related to prognosis, such as spread through air spaces (STAS) and histological grading. In contrast, the anatomical depth of invasion of lung cancer has not been well studied, and currently, only visceral pleura and main bronchus are the lung-specific structures that determine the T category of lung cancer.

We classified lung tissues into alveolar and extra-alveolar regions and investigated the prognostic impact of extra-alveolar invasion (EX) in 178 non-mucinous lung adenocarcinoma cases that underwent complete resection. EX was defined as periarterial, peribronchial/peribronchiolar, or interlobular septal invasion.

In the prognostic analysis of recurrence-free survival (RFS), all three EX factors were associated with poor prognosis, with EX identified as an independent prognostic factor. RFS in the pT1 EX(+) group was significantly shorter than that in the pT1 EX(-) group and was comparable to that in the pT2 group. The pT1 EX(-) group showed no lymph node metastasis at the time of surgery and no recurrence, regardless of invasive size, STAS status, or histological grade. RFS in the EX(+)/STAS(-) group was significantly shorter than that in the EX(-) group, and was better than that in the EX(+)/STAS(+) group. RFS in the EX(+)/G2 group was shorter than that in the EX(+)/G1 group, and was similar to that in the EX(+)/G3 group.

EX was found to be an independent prognostic factor which emphasizes the importance of depth of invasion in non-mucinous lung adenocarcinomas. Further investigation is needed to verify the validity of incorporating EX into the pathological T factor in future classification.