Systematic review of reflex biomarker testing and its influence on diagnostic and treatment timelines in cancer pathways

BACKGROUND: Reflex biomarker testing, where molecular assays are automatically requested at diagnosis, has been proposed to accelerate cancer care. However, its operational and clinical impact across tumor types has not been systematically evaluated. METHODS: A systematic review following PRISMA guidelines was conducted. MEDLINE, Embase, and gray literature (January 2000-August 2025) were searched for studies comparing reflex and clinician-initiated biomarker testing. Eligible studies reported quantitative outcomes for laboratory turnaround time, testing initiation intervals, or time to treatment. RESULTS: Thirty-two studies met inclusion criteria, spanning lung, skin, esophageal, breast, ovarian, colorectal, and hematological cancers. Reflex testing consistently shortened key intervals in diagnostic and treatment pathways. In non-small-cell lung cancer (n = 20), reductions were observed in turnaround time (1-38 days), initiation/request intervals (13-29 days), and time to treatment (1-44 days). Efficiencies increased use of first-line biomarker-directed therapy by 10-47%. Operational benefits included higher test uptake (7-50% increase) and lower failure rates (10-14% reduction). The magnitude of benefit varied by tumor type, biomarker panel, and implementation strategy. CONCLUSIONS: Reflex biomarker testing improves diagnostic efficiency and first-line therapy uptake across cancers. Its benefits are context-dependent, highlighting the need for tailored implementation strategies and evaluation of financial and clinical impact.