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

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.

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.

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.

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.