Prognostic Significance of Spread Through Airspaces (STAS) in Stage Ia/bN0 Non-small Cell Lung Cancer - An Evaluation in the JCOG0802/WJOG4607L Clinical Trial Patients.

INTRODUCTION

Tumor spread through air spaces (STAS) and histologic tumor grade have been reported as adverse prognostic factors in non-small cell lung cancer (NSCLC), yet their impact on the extent of surgical resection remains insufficiently defined. This study aimed to evaluate the prognostic impacts of STAS and tumor grade in stage IA patients (pT1a/bN0) from JCOG0802/WJOG4607L comparing segmentectomy and lobectomy.

METHODS

STAS and tumor grading were assessed in 593 tumors by 32 expert pulmonary pathologists across the world. The prognostic impact of STAS in lobectomy (n=294) versus segmentectomy (299) in relation to relapse-free survival (RFS) and overall survival (OS) was evaluated, as well as the association of STAS with histologic grading.

RESULTS

STAS was identified in 227 cases (38.3%) and was significantly associated with shorter relapse-free survival (RFS) and overall survival (OS) (RFS HR=2.204; OS HR=1.917; both p<0.001). Multivariable analysis confirmed STAS as an independent adverse factor for RFS (p<0.001) and OS (p=0.009). STAS was associated with higher local recurrence in both lobectomy and segmentectomy approaches (p=0.012 and p=0.002, respectively). STAS independently predicted shorter RFS in both lobectomy and segmentectomy subgroups, but only OS in the lobectomy subgroup. Among invasive non-mucinous adenocarcinomas, histologic grade 3 was strongly associated with STAS (p<0.001) and poor outcomes. Both STAS and grade 3 independently predicted shorter RFS, whereas only grade 3 predicted OS.

CONCLUSIONS

These findings reinforce STAS and high-grade adenocarcinoma as clinically significant prognostic factors and support their incorporation into risk stratification for stage IA (pT1a/bN0) NSCLC patients.