KRAS Mutations in Circulating Tumor DNA for Lung Cancer Diagnosis: A Comprehensive Meta-Analysis

<b>Background</b>: Mutations in the <i>KRAS</i> gene play a pivotal role in lung cancer development and progression and are becoming increasingly important in therapeutic decision-making. The detection of these mutations in circulating tumor DNA (ctDNA) has attracted attention as a minimally invasive diagnostic approach. However, the accuracy reported in different studies varies widely. <b>Methods</b>: We conducted a systematic review and meta-analysis in accordance with the PRISMA-DTA guidelines. Eligible studies evaluated the detection of <i>KRAS</i> mutations in ctDNA in plasma or serum for lung cancer diagnosis and reported sufficient data to construct 2 × 2 contingency tables. Primary pooled estimates of sensitivity, specificity and likelihood ratios were calculated using aggregated 2 × 2 contingency tables. Additionally, a bivariate random-effects model was applied in a secondary analysis to investigate between-study heterogeneity. <b>Results</b>: Nine diagnostic study arms comprising 691 patients met the inclusion criteria. Across all datasets, there were 255 true positives, 19 false positives, 136 false negatives, and 281 true negatives. The pooled sensitivity was 65.2%, while the pooled specificity was 93.7%. The positive likelihood ratio was 10.35, and the negative likelihood ratio was 0.37, resulting in a diagnostic odds ratio of 28.0, which indicates strong rule-in capability. Sensitivity showed moderate heterogeneity across studies. In contrast, specificity demonstrated minimal heterogeneity. <b>Conclusions</b>: ctDNA-based detection of <i>KRAS</i> mutations demonstrates high specificity but moderate sensitivity for diagnosing lung cancer. These findings suggest that a <i>KRAS</i> liquid biopsy could be a valuable complementary diagnostic tool, particularly when a tissue biopsy is not possible or is inadequate, and it could support more personalized decision-making as analytical technologies continue to advance.