Abstract
BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed non-small cell lung cancer (NSCLC) treatment, yet low response rates and resistance remain challenges. Emerging evidence suggests acupuncture may enhance ICI effectiveness by reprogramming immunosuppressive tumor microenvironments. METHODS: A retrospective analysis was conducted on 217 ICI-treated NSCLC patients. Patients who initiated acupuncture before median progression-free survival (mPFS, 8.87 months) of the overall population were classified as the acupuncture group (n = 97). Cox regression analysis was employed to evaluate the association between clinical characteristics and outcomes. Propensity score matching (PSM) was performed to mitigate selection bias. Subgroup and interaction analyses were conducted to evaluate potential effect modifiers. RESULTS: Acupuncture was significantly associated with improved mPFS (10.23 vs. 7.87 months, P = 0.036), while a numerical trend favoring acupuncture was observed in overall survival (mOS: 24.1 vs. 20.9 months, P = 0.352). Obvious benefits emerged in bone metastasis patients, with the acupuncture group reducing progression risk by 76% (HR = 0.24, 95% CI 0.14-0.42, P < 0.001) and death risk by 53% (HR = 0.47, 95% CI 0.21-1.03, P = 0.049). Conversely, PD-L1-positive subgroups exhibited no trend of improvement (subgroup HR > 1.0), with interaction HRs > 2.0 indicating potential impairment of ICI efficacy. The results of post-PSM data suggest that acupuncture was independently associated with improved PFS (aHR = 0.62, 95% CI 0.41-0.94, P = 0.024). CONCLUSION: Our findings suggest a positive association between acupuncture and improved outcomes in ICI-treated NSCLC patients, particularly in those with bone metastasis, underscoring the potential role of acupuncture in the integrative management of cancer. However, biomarker-guided patient stratification is essential for integrating acupuncture into oncology care.