Optimizing neoadjuvant chemoimmunotherapy cycles based on radiologic response improves efficacy and survival in non-small cell lung cancer

Background: The optimal number of neoadjuvant chemoimmunotherapy cycles in non-small cell lung cancer (NSCLC) remains unclear. This study evaluates whether determining the number of treatment cycles based on interim radiologic response after the initial two cycles impacts therapeutic efficacy and survival.

Methods: We retrospectively identified 395 patients with stage IIB–IIIB NSCLC who received 2–4 cycles of neoadjuvant chemoimmunotherapy between September 2020 and April 2024. Propensity score matching (PSM) was conducted between 2-cycle and 3–4-cycle groups, yielding 155 matched pairs. Patients were further stratified into partial response (PR) and stable disease (SD) subgroups based on their radiologic response after the first 2 cycles. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method, and logistic regression was used to identify factors associated with postoperative complications.

Results: In the overall matched cohort, receiving 3–4 cycles of neoadjuvant chemoimmunotherapy was significantly associated with improved OS (P=0.01) and RFS (P=0.03), increasing 24-month RFS rates from 72.5% to 78.2%. Such improvements were observed without an increase in the risk of postoperative complications. Subgroup analysis revealed 3–4 cycles significantly prolonged RFS in patients with SD after 2 cycles (P=0.045), improving 24-month RFS from 60.9% to 72.8%. In this subgroup, continued treatment also significantly reduced residual viable tumor (RVT) (20.0% vs. 57.5%, P=0.04) and showed a trend toward an improved major pathological response (MPR) rate (43.8% vs. 31.8%). Conversely, no additional benefits were observed in patients who achieved an early PR.

Conclusions: For patients with radiologic SD after 2 cycles, continuing treatment to 3–4 cycles was associated with further reduction in RVT and prolonged RFS without increasing postoperative complications. By contrast, minimal benefit was observed with continued therapy in patients who achieved PR.