Association between the number of cycles of neoadjuvant chemoimmunotherapy and treatment outcomes in stage II-IIIB non-small cell lung cancer

Abstract

Neoadjuvant chemoimmunotherapy has improved outcomes in resectable non-small cell lung cancer (NSCLC), yet the optimal number of treatment cycles remains uncertain. This study evaluated the association between the number of treatment cycles and treatment outcomes in patients with stage II-IIIB NSCLC and explored factors associated with pathological response. This was a two-center retrospective observational study. A total of 408 patients with stage II-IIIB NSCLC who underwent surgical resection after neoadjuvant chemoimmunotherapy between January 2021 and February 2025 were included. Patients were grouped by treatment-cycle number into ≤2 (n = 185), 3 (n = 162), and ≥4 (n = 61). Treatment-cycle number was not predefined; patients with favorable early responses and resectable disease were more likely to proceed to surgery after ≤2 cycles, whereas those with suboptimal responses or borderline resectability more often received additional cycles. Primary endpoints were major pathological response (MPR) and pathological complete response (pCR). Secondary endpoints included objective response rate (ORR), lymph node downstaging, disease-free survival (DFS), and grade ≥3 treatment-related adverse events (TRAEs). The cohort was 93.4% male and 6.6% female, and 69.4% had squamous-cell histology. Overall MPR and pCR rates were 55.9% and 31.4%, respectively. MPR rates were 58.4%, 56.2%, and 47.5% in the ≤2-, 3-, and ≥4-cycle groups, while pCR rates were 32.4%, 31.5%, and 27.9%, respectively. No significant differences were observed among groups for MPR, pCR, ORR, lymph node downstaging, DFS, or grade ≥3 TRAEs (all P > 0.05). After adjustment for baseline characteristics, cycle number remained unassociated with pathological response. Preoperative radiological response and high PD-L1 expression were independently associated with higher odds of both MPR and pCR (both P < 0.05). In this selected surgical cohort with non-random cycle allocation, treatment-cycle number was not significantly associated with pathological response. In exploratory analyses of selected early responders, additional cycles were not associated with higher MPR or pCR rates. Radiological response and baseline PD-L1 expression were associated with pathological response.