BACKGROUND: The safety, feasibility, and potential benefits of uniportal video-assisted thoracoscopic surgery (U-VATS) pneumonectomy remain to be investigated. This study aimed to evaluate the postoperative outcomes, survival prognosis, and recurrence patterns in patients undergoing U-VATS versus those undergoing open pneumonectomy. The feasibility of U-VATS pneumonectomy in patients receiving neoadjuvant systemic therapy was also assessed. METHODS: Patients with non-small cell lung cancer (NSCLC) underwent thoracic surgeries at the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from January 2017 to December 2022. Among these patients, those who underwent U-VATS or open pneumonectomy were included in our study. Propensity score matching (PSM) with a 3:1 ratio was conducted to balance the baseline characteristics between the groups. We compared perioperative outcomes and recurrence patterns between the two groups. RESULTS: A total of 457 patients who underwent pneumonectomy were included in our study, with 348 in the open pneumonectomy group and 109 in the U-VATS group. After PSM, 334 patients (231 in the open group and 103 in the U-VATS group) were available for subsequent analyses. Patients who underwent U-VATS pneumonectomy experienced shorter postoperative hospital stays (P<
0.002). No significant differences were observed in the 5-year overall survival (OS) rate (P=0.19) or the 5-year recurrence-free survival (RFS) rate (P=0.37) between the two groups. Additionally, subgroup analysis of patients receiving neoadjuvant systemic therapy indicated those in the U-VATS group did not exhibit significant differences in recurrence patterns between the two groups. CONCLUSIONS: Patients with NSCLC undergoing U-VATS pneumonectomy exhibit postoperative outcomes, survival rates, and recurrence patterns that are not inferior to those of patients undergoing open pneumonectomy.