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).