Surgical resection is the preferred treatment for early-stage non-small cell lung cancer (NSCLC), often accompanied by adjuvant chemotherapy in tumors with specific high-risk characteristics. However, concerns have been raised regarding the traditionally reported 5% 5-year survival advantage associated with these treatments. Therefore, a study aimed to reassess the effectiveness of adjuvant chemotherapy using contemporary real-world datasets.

Researchers conducted a retrospective cohort study using data from the National Cancer Database to evaluate the efficacy of adjuvant chemotherapy in early-stage node-negative NSCLC patients with high-risk features, as defined by National Comprehensive Cancer Network guidelines. Eligible patients had a tumor size between 3-5cm and at least one high-risk clinical or pathologic feature, such as poor differentiation, tumor size ≥4cm, non-anatomic wedge resection, inadequate lymph node evaluation, vascular invasion, or visceral pleural involvement. The study employed average treatment effect on the treated (ATT) weighting to compare outcomes between the chemotherapy and observation groups, ensuring comparability in demographic, tumor, and treatment-related variables. The primary outcome assessed was overall survival (OS). The findings were further validated using an independent cohort from the US Veteran Health Administration (VHA).

A total of 10,812 patients diagnosed with early-stage NSCLC, all exhibiting at least one high-risk feature, were included in the study. The frequencies of high-risk features were as follows: tumor size ≥4cm (n = 3,271, 30.3%), poor differentiation (n = 9,454, 87.4%), visceral-pleural invasion (n = 2,542, 23.5%), vascular invasion (n = 1,742, 16.11%), non-anatomic wedge resection (n = 781, 7.2%), and inadequate nodal sampling (n = 6,306, 58.3%). Surprisingly, only a small proportion of patients, 1,427 (13.2%), received adjuvant chemotherapy. In the ATT-weighted analysis, out of the total patient cohort, 1,261 (49.7%) individuals received adjuvant chemotherapy, while 1,278 (50.3%) opted for observation. The 5-year overall survival rate in the chemotherapy group was found to be 70.0% (95% CI 67.1-72.7) compared to 62.0% (95% CI 60.2-63.7) in the observation group, indicating an absolute 5-year survival difference of 8.0%. In the VHA cohort, which accounted for 11.3% of patients, the 5-year overall survival rate was 64.0% (95% CI 51.4-74.2) in the chemotherapy group and 56.2% (95% CI 48.3-63.4) in the observation group, showing an absolute 5-year survival difference of 7.8%.

These findings highlight a significantly greater benefit of adjuvant chemotherapy in eligible patients with high-risk clinical and pathologic features, surpassing commonly reported statistics. As more advanced treatment options emerge for early-stage NSCLC, adherence to guidelines for adjuvant and neoadjuvant therapy may disproportionately improve outcomes following curative-intent surgical resection.