Potential of Minimal Residual Disease in Guiding Adjuvant Therapy Decisions in Non–Small Cell Lung Cancer

PURPOSE Circulating tumor DNA (ctDNA)–based minimal residual disease (MRD) detection has become a strong prognostic stratification factor in postoperation non–small cell lung cancer (NSCLC). Here, we sought to investigate the guiding potential of MRD in informing adjuvant therapy (AT) decisions. MATERIALS AND METHODS Patients with stage IA to IIIB NSCLC who had undergone confirmed R0 resection were enrolled. Blood samples were collected 1 month after surgery before initiation of AT (landmark) and longitudinally every 3-6 months since surgery. Postoperative AT was conducted according to the guideline recommendations, and regular radiographical examinations were recommended for relapse surveillance. MRD detection was conducted using the MinerVa platform (Genecast Precision Diagnostic Co., Ltd. Wuhan, China) using a tumor-informed strategy based on a fixed next-generation sequencing panel spanning 769 cancer-related genes. RESULTS One hundred sixty-five patients were included in this study, with 35 (21.2%) relapses. At landmark, positive MRD was associated with shorter disease-free survival (DFS) than negative MRD ( P < .001, hazard ratio, 12.0). MRD was an independent risk factor for shorter DFS, irrespective of the disease stage and high-risk factors. In the case of negative landmark MRD, there was no significant difference between the DFS of (1) those who received AT and those who did not in stage IB patients with high-risk factors ( P = .974), (2) epidermal growth factor receptor ( EGFR )–mutant patients with or without adjuvant chemotherapy before adjuvant targeted therapy ( P = .502), and (3) EGFR / ALK wild-type with or without adjuvant immunotherapy ( P = .534). Clearance of ctDNA during AT was associated with a better prognosis than persistently detected ctDNA ( P < .001). CONCLUSION ctDNA-based MRD stratifies prognosis after curative resection in NSCLC, with MRD negativity indicating limited benefit from treatment in selected patients and ctDNA clearance reflecting improved outcomes. These findings support the clinical utility of MRD-guided adjuvant treatment strategies.