Neoadjuvant chemoimmunotherapy versus chemoradiotherapy for non-small cell lung cancer: a comparative analysis of clinical outcomes and pathologic response.

Background: While neoadjuvant chemoimmunotherapy (neoCIT) has been increasingly adopted for locally advanced non-small cell lung cancer (NSCLC), there is a lack of direct comparison with neoadjuvant concurrent chemoradiotherapy (neoCCRT), which has long been used to enhance local tumor control. This gap presents a clinical dilemma, as both approaches are associated with distinct mechanisms and potential trade-offs in efficacy and safety. In this study, we aimed to compare the clinical outcomes and pathological responses to neoCIT and neoCCRT in patients with locally advanced NSCLC. Methods: We retrospectively analyzed 71 patients with locally advanced NSCLC who received either neoCCRT (n=38) or neoCIT (n=33), followed by surgical resection between January 2010 and April 2024. Pathological response was assessed using the International Association for the Study of Lung Cancer criteria, and clinical outcomes, including postoperative complications, recurrence, and survival, were compared. Results: Baseline characteristics were balanced except for histology. Squamous carcinoma was predominant in the neoCIT group, whereas non-squamous histology was more common in the neoCCRT group. The neoCCRT group achieved significantly higher major pathological response (MPR) rates (55.3% vs. 30.3%, P=0.03), although pathological complete response rates were similar (15.8% vs. 15.2%). Two-year recurrence (31.6% vs. 18.2%, P=0.20), postoperative complications (21.1% vs. 27.3%, P=0.54), and survival outcomes did not differ significantly between groups. Conclusions: neoCCRT and neoCIT demonstrate comparable safety and survival outcomes in patients with locally advanced NSCLC. While neoCCRT led to higher MPR rates, this did not correspond to improved survival. Treatment selection should be individualized based on tumor burden, histologic subtype, and risk of distant metastasis.