The influence of the administration sequence of neoadjuvant immunotherapy combined with chemotherapy on the postoperative pathological response of stage IIA-IIIB non-small cell lung cancer

This study aimed to evaluate whether the within-cycle sequence of neoadjuvant immunochemotherapy influences postoperative pathological response in patients with stage IIA–IIIB non-small cell lung cancer (NSCLC). We retrospectively enrolled 192 patients with stage IIA–IIIB NSCLC who received neoadjuvant immunochemotherapy. Patients were divided into Group A (chemotherapy on day 1 followed by immunotherapy on day 2, n = 122) and Group B (immunotherapy on day 1 followed by chemotherapy on day 2, n = 70). Propensity score matching (1:1, caliper = 0.2) created 62 matched pairs. The primary endpoint was postoperative pathological response including pathological complete response and major pathological response. Conditional logistic regression was used, and E‑values were calculated for sensitivity analysis. Secondary endpoints included objective response rate (ORR), safety, and perioperative outcomes. After matching, baseline characteristics were well balanced. The pathological response rate was higher in Group A than in Group B (50.00% vs. 30.64%; univariate OR = 2.33, 95%CI 1.07–5.09, P = 0.033; multivariable OR = 4.78, 95%CI 1.24–18.46, P = 0.023). E‑value analysis suggested that the observed association may be relatively robust to unmeasured confounding (univariate E = 4.09, multivariable E = 9.03). ORR was also higher in Group A (72.58% vs. 51.65%; OR = 2.62, 95%CI 1.16–5.93, P = 0.020). Grade ≥ 3 treatment‑related adverse events were similar between groups (35.48% vs. 29.03%, P = 0.494). Operative time was longer in Group A (180 vs. 165 min, P = 0.037), but no differences were observed in R0 resection rate, postoperative complications, or other surgical outcomes. In patients with stage IIA–IIIB NSCLC, the within-cycle administration sequence of chemotherapy followed by immunotherapy was associated with a higher postoperative pathological response rate. This dosing sequence may have clinical optimization value, but further validation through prospective studies is still needed.