Risk Stratification and Adjuvant Chemotherapy for High-Risk Stage IA Lung Adenocarcinoma: The Unmet Needs.

Introduction: To identify high-risk patients for recurrence in resected stage IA lung adenocarcinoma and evaluate the impact of adjuvant chemotherapy (ACT) on their prognosis, as well as explore potential novel adjuvant therapies.

Methods: Consecutive stage IA patients with ≥ 5% solid or micropapillary subtypes were analyzed. A nomogram was developed using Cox proportional hazards regression to predict recurrence-free survival (RFS). In the high-risk group after stratification, RFS was compared between patients receiving ACT and those under observation, as well as between patients with and without driver gene alterations.

Results: This real-world study included 1328 patients, with a 5-year RFS of 79.0%. T stage and predominant subtype were independent risk factors for RFS. Patients with T1c or solid/micropapillary-predominant tumors were stratified into a high-risk group (n = 483) using the nomogram. A significant difference in 5-year RFS was observed between the high- and low-risk groups (73.6% vs. 84.3%, p < 0.001). Among high-risk patients, sixty-seven (13.8%) received ACT; however, there was no improvement in 5-year RFS compared to observation alone (69.1% vs. 75.0%, p = 0.655). Testing rates for EGFR mutation and ALK fusion among high-risk patients were only 52.4% and 43.9%, respectively, while mutation rates reached up to 55.7% and 9.4%, respectively. These molecular alterations exhibited numerically worse 5-year RFS compared to wild-type (EGFR mutation, 70.6% vs. 87.8%, p = 0.108; ALK fusion, 66.3% vs. 73.6%, p = 0.404), though not significant.

Conclusions: ACT failed to meet the needs of stage IA patients with histological high-risk features. Further exploration of effective adjuvant target therapies is warranted for this patient subgroup.