Real-World Utilization of Tissue-Free ctDNA MRD Testing in Non-Small Cell Lung Cancer Across Asia-Pacific and the Middle East: A Descriptive Cohort Analysis and Illustrative Case Series

Introduction: Circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) testing is emerging as a tool to refine relapse risk and guide surveillance after curative-intent therapy for non-small cell lung cancer (NSCLC). Tissue-free (plasma-only) MRD assays may improve feasibility where tumor tissue is limited. Prospective and trial-embedded studies have established that ctDNA MRD detected after curative-intent therapy is prognostic for recurrence in NSCLC, but how tissue-free MRD testing is deployed in routine care in Asia-Pacific and the Middle East (AMEA) has not been described. We characterized ordering patterns and first-test positivity in an AMEA cohort. In this descriptive cohort (159 NSCLC patients; 257 samples), 40.9% of patients underwent more than one MRD test, with a median interval of 4.9 months between the first two tests; first-test MRD positivity was 15.7% (25/159; 95% CI 10.9–22.2) with rates of 0% (0/9; 95% CI 0.0–29.9), 8.8% (5/57; 95% CI 3.8–18.9), 21.5% (17/79; 95% CI 13.9–31.8) and 21.4% (3/14; 95% CI 7.6–47.6), respectively, across stages I, II, III, and oligometastatic stage IV disease. No hypothesis testing was performed, and the stage I and oligometastatic stage IV subgroups are small, so the confidence intervals overlap widely and apparent between-stage differences should not be interpreted as a stage effect. Case Presentation: Six illustrative cases involving patients with stage II–IVB describe the use of MRD testing in routine clinical care. The cases were selected purposively, not consecutively, to span the contexts in which the results were interpreted: a positive result shortly before radiographic nodal recurrence (Case 1); a positive result during long-term adjuvant osimertinib preceding isolated mediastinal relapse (Case 2); a transient positive result with subsequent clearance and radiographic regression (Case 3); a positive result that prompted PET-CT revealing occult metastatic disease (Case 4); serially negative results concordant with sustained radiographic remission (Case 5); and a positive result that prompted comprehensive genomic profiling identifying an actionable KRAS G12C alteration (Case 6). Conclusions: Across Asia-Pacific and the Middle East, tissue-free MRD testing in NSCLC was used primarily during surveillance and often serially; first-test positivity was 15.7% (95% CI 10.9–22.2) overall, with wide and mutually overlapping confidence intervals across stages. The cases illustrate that MRD results may prompt diagnostic evaluation when interpreted alongside imaging and other clinical findings, but they are purposively selected, and treatment changes that followed a result are reported as description, not as evidence of benefit. No assay performance characteristic is estimated. These findings are hypothesis-generating; prospective, MRD-directed trials with standardized timepoints, thresholds, confirmatory strategies and pre-specified clinical actions are needed before MRD results can guide treatment.