Differential gene detection and turnaround time between tissue and Guardant360 liquid biopsy next-generation sequencing across solid malignancies.

e15066 Background: Circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is increasingly used for genomic profiling in metastatic solid tumors, yet real-world differences in mutation detection, cross-platform concordance and turnaround time (TAT) across tumor types remain incompletely defined. We compared these metrics between tissue NGS and Guardant360 liquid biopsy in a large, heterogeneous clinical cohort. Methods: We retrospectively analyzed patients with metastatic solid malignancies who underwent tissue NGS and/or Guardant360 testing during routine care at the Cancer Center of Kansas. Cancer type, number of pathogenic or likely pathogenic alterations, and TAT (days from specimen collection to finalized report) were abstracted. Outcomes were summarized overall and by major tumor groups (breast, lung, prostate, colorectal, other). Among patients tested with both types of biopsies, concordance of recurrent mutations was evaluated descriptively. Analyses were conducted under prespecified null hypotheses of no difference in mutation yield or TAT between platforms. Results: A total of 880 evaluable NGS assays were included (227 tissue-based, 653 Guardant360). Guardant360 demonstrated a higher mean mutation yield than tissue NGS overall (mean 6 vs 5; median 5 vs 4). Higher Guardant360 yields were observed in breast (mean 8 vs 4), colorectal (9 vs 5), and other solid tumors (6 vs 5), while yields were similar in lung cancer (6 vs 6) and modestly higher in prostate cancer (5 vs 3). Guardant360 was associated with substantially shorter TAT overall (median 7 vs 20 days; mean 9 vs 67 days), with consistent differences across tumor subgroups; prostate cancer showed the smallest differential (median 7 vs 5 days). Among 136 paired tests, concordance varied by gene and tumor type. TP53, KRAS, APC, EGFR, and PIK3CA were the most frequently shared alterations, though absolute overlap was limited (e.g., TP53 detected on both platforms in 81 cases vs 101 tissue-only and 421 Guardant360-only detections). Overlap patterns reflected tumor biology, with lung cancers contributing most TP53 and EGFR concordance and colorectal cancers predominating in APC and KRAS overlap. Conclusions: In this large real-world, multi-tumor analysis, Guardant360 ctDNA testing demonstrated comparable or higher mutation detection and markedly faster turnaround time than tissue NGS, while revealing biologically meaningful but incomplete genomic concordance. Early liquid biopsy may substantially shorten time to molecular results without compromising detection across diverse solid malignancies, informing treatment selection when tissue testing is delayed or limited. Integrated tissue–liquid sequencing may optimize comprehensive genomic profiling and precision oncology decision-making in metastatic disease.