Grade-driven adjuvant chemotherapy benefit in high-risk stage IB NSCLC: a retrospective cohort study

The benefit of adjuvant chemotherapy (ACT) in stage IB non-small cell lung cancer (NSCLC) remains controversial, particularly for patients with high-risk features [visceral pleural invasion (VPI), lymphovascular invasion (LVI), poor differentiation]. This study aimed to evaluate the efficacy of ACT in this cohort.

We retrospectively analyzed 356 patients with stage IB [American Joint Committee on Cancer (AJCC) 9th edition] lung adenocarcinoma treated from 2016 to 2019, of whom 276 with at least one high-risk factor were included in the study. Propensity score matching (PSM) was used to balance baseline characteristics (n=106 per group). Disease-free survival (DFS) and overall survival (OS) were compared between the ACT and non-ACT groups.

ACT significantly improved DFS [hazard ratio (HR) =0.471, P=0.001] and OS (HR =0.519, P=0.03). Subgroup analysis revealed that the benefit was grade-dependent: patients with poorly differentiated (G3) tumors had a 66.5% lower risk of recurrence with ACT (HR =0.335, P=0.001), while those with moderately differentiated (G2) tumors derived no significant benefit (HR =1.041, P=0.91). High-grade histologic patterns (solid, micropapillary, and complex glandular), LVI, and tumor size were independent predictors of poor survival. VPI status did not significantly influence ACT efficacy (P=0.95).

ACT provides survival benefits for stage IB NSCLC patients with high-risk features, especially in poorly differentiated (G3) tumors. Histologic grading might serve as a useful tool to guide ACT decisions and to avoid potential overtreatment in moderately differentiated (G2) subgroups.