Early Effects of Bronchoscopic Cryotherapy in Metastatic Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Single-Center Prospective Study.

Background/Objectives: Cryotherapy is used for local tissue destruction through rapid freeze-thaw cycles. It induces cancer cell necrosis followed by inflammation in the treated tumor microenvironment, and it stimulates systemic adaptive immunity. Combining cryotherapy with immunotherapy may provide a sustained immune response by preventing T cell exhaustion. Methods: Fifty-five patients with metastatic non-small cell lung cancer who had received no prior treatment were randomized into two groups in a 1:1 ratio: the bronchoscopic cryotherapy group or the control group. Patients received up to four cycles of pembrolizumab as monotherapy or in combination with platinum-based chemotherapy. Immune-related adverse events (irAEs), complications, tumor size changes, overall response rate (ORR), and disease control rate (DCR) were evaluated. Results: Lung tumors, treated with cryotherapy, demonstrated continuous reduction from the baseline (22.4 cm2 vs. 14.4 cm2 vs. 10.2 cm2, p < 0.001). Similar changes were observed in pulmonary tumors in the control group (19.0 cm2 vs. 10.0 cm2, p < 0.001). The median change in pulmonary tumors between two groups was not significant (-42.9% vs. -27.7%, p = 0.175). No significant differences were observed in the ORR (28.6% vs. 23.1%, p = 0.461) or target lesion decrease (-24.0% vs. -23.4%, p = 0.296) between the groups. However, the DCR was significantly higher in the cryotherapy group (95.2% vs. 73.1%, p = 0.049). No cases of serious bleeding during cryotherapy or pneumothorax were observed. Six patients (25.0%) in the cryotherapy group and eight (26.7%) in the control group experienced irAEs. Conclusions: Our study demonstrated that combined bronchoscopic cryotherapy and immunotherapy with or without chemotherapy may reduce the rate of progressive disease in metastatic non-small cell lung cancer patients while maintaining a satisfactory safety profile.