Patterns of Failure in Synchronous Metastatic Non-Small Cell Lung Cancer Without Driver Alterations According to Metastatic Burden

Background: Patterns of failure (POFs) after first-line immune checkpoint inhibitor (ICI)-based therapy in patients with synchronous metastatic non-small cell lung cancer (NSCLC) without oncogenic driver alterations may guide the selection of candidates for local consolidative therapy (LCT). Methods: We retrospectively evaluated patients diagnosed with synchronous metastatic NSCLC between January 2017 and December 2023. Patients with oncogenic driver alterations, those who did not receive ICIs as first-line therapy, or those who lacked follow-up imaging were excluded. Patients were stratified into four groups according to the number of metastatic lesions: 1, 2, 3–5, and >5 lesions. POFs were classified as original site recurrence (OSR) or new site recurrence with or without OSR (NSR). Competing risk analyses were performed. Results: A total of 221 patients were analyzed, with a median follow-up of 28.1 months. Initial failure patterns did not differ significantly across lesion-number groups (p = 0.417). The 2-year cumulative incidence of OSR was not significantly different between the groups (p = 0.828). A trend toward a lower NSR was observed in patients with a single metastatic lesion (p = 0.063). Analysis of subsequent failures revealed a higher rate of NSR in the 1-lesion group than in the other groups (p = 0.043). No independent predictors of OSR were identified in multivariate analysis. Conclusions: In synchronous metastatic driver-negative NSCLC treated with first-line ICI-based therapy, both OSR and NSR were common and not clearly associated with metastatic burden, suggesting that lesion number alone may be insufficient for selecting candidates for LCT.