Neoadjuvant immunotherapy and surgery in patients with stage IIIB-IIIC (N3) non-small cell lung cancer.

8045 Background: Stage IIIB-IIIC (N3) non-small cell lung cancer (NSCLC) is generally seen as unresectable, and Durvalumab following concurrent chemoradiotherapy (CCRT) is the standard of care for these patients. The use of immune checkpoint inhibitor (ICI) in neoadjuvant therapy has resulted in unprecedented rates of pathological response and lymph node downstaging, which has made resecting previous unresectable disease possible. However, it remains uncertain whether certain N3 patients may derive survival benefit from surgery after neoadjuvant immunotherapy. Methods: This multicenter retrospective study included patients with cN3 NSCLC who received inducing immunochemotherapy and completed surgery. As a comparison, patients with cN3 NSCLC who received ICI following CCRT, ICI plus CCRT, and CCRT following inducing immunochemotherapy were also included. 1:1 Propensity score matching (PSM) was implemented to balance important baseline characteristics included gender, age, smoking history, histologic type, differentiated degree, cT stage between patients with surgery and radiotherapy. Log-rank test was used to compared progression-free survival (PFS). Results: The median follow-up time of 82 patients with surgery and 114 patients with radiotherapy was 28.1 months and 21.8 months, respectively. In patients with surgery, 29 patients reach complete pathological response (pCR) and 53 patients reached node clearance. After PSM, 74 patients with surgery and 74 patients with radiotherapy showed balanced baseline characteristics. Before PSM, patients with surgery displayed a significant advantage in median PFS (24.6 months vs 21.3 months, p=0.040) but this advantage disappeared after PSM (31.3 months vs 30.8 months, p=0.132). In post-treatment subgroup analyses, patients reached pCR had better PFS than patients with radiotherapy (median PFS not reach vs 30.8 months, p=0.001). In addition, patients reached node clearance also had better PFS than patients with radiotherapy (median PFS not reach vs 30.8 months, p=0.010). In pre-treatment subgroup analyses, surgery did not outperform radiotherapy in male or female patients, smokers or nonsmokers, squamous or non-squamous carcinoma and poorly differentiated carcinoma. In patients with high or moderately differentiated tumors, patients with surgery had better PFS than patients with radiotherapy (median PFS not reach vs 13.2 months, p=0.001). Conclusions: In patients with cN3 NSCLC, surgery after neoadjuvant immunochemotherapy do not transcend ICI with CCRT in PFS. Only patients with high or moderately differentiated tumors, or reached pCR, node clearance after surgery have better PFS than patients with radiotherapy. Prospective clinical is needed to evaluate the benefit of surgery after neoadjuvant immunotherapy for cN3 NSCLC.