Clinical outcomes with definitive surgery or radiotherapy after neoadjuvant immunochemotherapy in stage II-III NSCLC: Full cohort pragmatic analysis.

8059 Background: Recently, several landmark randomized controlled trials on neoadjuvant immunochemotherapy (NIC) have significantly changed the treatment paradigm for locally advanced NSCLC. However, 8.8-19.0% of patients (pts) receiving NIC did not undergo surgery due to various reasons. The treatment strategies and clinical outcomes following NIC for stage II-III NSCLC, encompassing both surgical and non-surgical approaches, remain unclear. Methods: We conducted a multicenter, retrospective cohort study involving stage II-III (T1-4N0-2) pts who underwent radical surgery or radiotherapy after NIC in routine clinical practice across 12 medical centers in China between January 2018 and December 2023. For pts receiving radical radiotherapy, we documented the reasons for non-surgical management, and planned surgical procedures. Propensity score matching (PSM) was performed based on age, gender, smoking history, clinical stage, and histology to balance the clinicopathologic characteristics. The primary outcomes were progression free survival (PFS) and overall survival (OS). Results: 967 pts were included: 683 (70.6%) underwent surgery and 284 (29.4%) received radiotherapy. Reasons for radiotherapy after NIC included potentially resectable but declined surgery after shared decision-making (65.5%, 186/284), functionally unresectable (14.4%, 41/284), and technically unresectable (20.1%, 57/284), respectively. At the database lock (November 24, 2024; median follow-up: 23.3 months), PFS (HR: 0.32, 95% CI: 0.23-0.44, p<0.001) and OS (HR: 0.41, 95% CI: 0.26-0.66, p<0.001) were significantly improved in pts undergoing surgery after PSM. PFS across most key subgroups favored surgery: stage IIIA (HR: 0.34, 95% CI: 0.21-0.55, p <0.001), stage IIIB (HR: 0.39, 95% CI: 0.24-0.63, p <0.001), (planned) pneumonectomy (HR: 0.47, 95% CI: 0.26-0.85, p=0.013) and (planned) lobectomy (HR: 0.24, 95% CI: 0.13-0.45, p<0.001). However, the pts planned for pneumonectomy in radiotherapy group exhibited similar OS compared to those undergoing pneumonectomy. Conclusions: Among pts with locally advanced NSCLC treated with NIC, radical surgery demonstrated long-term clinical benefit. Subgroups N (S) N (R) HR (95% CI) p-value PFS All patients 365 183 0.32 (0.23, 0.44) <0.001 Disease stage II 34 17 0.05 (0.01, 0.24) <0.001 IIIA 175 89 0.34 (0.21, 0.55) <0.001 IIIB 142 76 0.39 (0.24, 0.63) <0.001 (Planned) Surgery Pneumonectomy 66 66 0.47 (0.26, 0.85) 0.013 Left pneumonectomy 46 46 0.52 (0.26, 1.04) 0.066 Lobectomy 106 54 0.24 (0.13, 0.45) <0.001 OS All patients 365 183 0.41 (0.26, 0.66) <0.001 Disease stage II 34 17 0.08 (0.01, 0.44) 0.004 IIIA 175 89 0.60 (0.28, 1.25) 0.17 IIIB 142 76