Circulating tumor DNA as part of the routine work-up for patients with suspected advanced lung cancer

Liquid biopsy (LB) is a useful tool in patients with advanced non-small cell lung cancer (aNSCLC) to detect actionable molecular alterations and thereby allow genotype-matched therapies. Currently, LB is recommended for individuals diagnosed with aNSCLC who have an insufficient tissue sample or difficult-to-reach tumour tissue. Despite the potential advantages of LB, its incorporation into the standard diagnostic work-up for all newly diagnosed patients with aNSCLC is lacking. Our study aimed to evaluate whether addition of plasma circulating tumor DNA (ctDNA) next generation sequencing (NGS) testing early in the diagnostic work-up for patients with aNSCLC can improve the time to molecular results and treatment initiation. This was a single-centre quality improvement initiative with two cohorts of patients. Patients in the 'ctDNA cohort' had plasma ctDNA testing in addition to the standard diagnostic work-up. The 'reference cohort' was a parallel group of patients who had the standard work-up (no LB). Tissue biopsy and reflex tissue NGS testing were done in both cohorts. ctDNA testing shortened the time to molecular results in the ctDNA cohort compared to the reference cohort (median, 14 vs 35 days; p = 0.01), the time from first respirology/thoracic surgery consult to molecular results (median, 22 vs 48 days respectively; p = 0.01), and the time from medical oncology consultation to initiation of first-line treatment (median, 12 vs 22 days; p = 0.01). In conclusion, in a publicly funded and single-payer healthcare system, ctDNA testing as part of the standard work-up for patients with aNSCLC provides molecular results significantly faster than tissue-based testing and shortens the time to treatment initiation.