Introduction: This study aims to evaluate the efficacy and safety of cryoablation combined with pembrolizumab treatment versus cryoablation alone in patients with advanced non-small cell lung cancer (NSCLC). Methods: This retrospective study was conducted from February 2018 to October 2021. A total of 90 patients with NSCLC (AJCC stage IIIB/IV) were included, with 36 patients receiving cryoablation combined with pembrolizumab (group A) and 54 patients receiving cryoablation alone (group B). The primary outcome measures included objective response rate (ORR), overall survival (OS), and progression-free survival (PFS), immune responses, and adverse events serving as secondary endpoints. Risk factors for OS and PFS were identified using univariate and multivariate analyses. Results: No treatment-related deaths were observed. Group A demonstrated a higher ORR (75.0% vs. 61.1%), longer median OS (28.1 months vs. 24.2 months), and longer median PFS (12.8 months vs. 8.4 months) compared to Group B. Additionally, group A showed significant increases in CD3+, CD4+, and CD8+ T cells, and elevated levels of interleukin-2, interleukin-6, TNF-β, and interferon-γ. The multivariate analysis showed the combination of cryoablation and pembrolizumab was an independent prognostic factor for OS and PFS. Conclusions: Cryoablation combined with pembrolizumab significantly improves clinical outcomes in advanced NSCLC patients compared to cryoablation alone, highlighting the potential of this combination therapy in enhancing antitumor immunity and prolonging survival.

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