Prognostic factors for poor outcomes and the predictive role of circulating tumor DNA in immunotherapy for advanced non-small cell lung cancer

Advanced non-small cell lung cancer (NSCLC) demonstrates considerable variability in therapeutic response. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for predicting immunotherapy efficacy and progression-free survival (PFS). This study investigates the prognostic relevance of ctDNA levels along with other clinical parameters in patients treated with immune checkpoint inhibitors. A retrospective analysis was conducted on 118 patients with stage IIIB/IV NSCLC who received Tislelizumab between January 2021 and December 2023 at Quanzhou First Hospital. ctDNA concentrations were assessed before and after treatment using quantitative polymerase chain reaction (qPCR). Based on RECIST 1.1 criteria, patients were classified into the responder group (complete or partial response) and the nonresponder group (stable or progressive disease). Statistical methods included receiver operating characteristic curve analysis, Kaplan-Meier survival estimates, and Cox proportional hazards regression. Posttreatment ctDNA levels were significantly lower in responders compared with nonresponders (2.72 ± 1.11 vs 4.18 ± 1.54 ng/μL, P < .001). Receiver operating characteristic analysis yielded an AUC of 0.821, with sensitivity and specificity of 80.9% and 79.8% at a cutoff value of 3.59 ng/μL. Kaplan-Meier analysis demonstrated that patients with low ctDNA had longer median PFS (8.6 months) than those with high ctDNA (5.5 months, P < .001). Multivariate Cox regression identified ctDNA levels and treatment modality as independent predictors of PFS. ctDNA serves as a reliable predictor of immunotherapy response and PFS in advanced NSCLC. Incorporating ctDNA monitoring into routine practice may enhance patient stratification and optimize therapeutic outcomes.