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

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. 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. 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. 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. Reflex biomarker testing is a process where molecular tests are automatically requested at the time of cancer diagnosis, rather than waiting for a clinician to request them. This approach has been suggested to speed up diagnosis and treatment, but its effects across different cancer types have not been fully studied. We reviewed 32 studies published between 2000 and 2025 that compared reflex testing with clinician-initiated testing. These studies covered a range of cancers, including lung, skin, esophageal, breast, ovarian, colorectal, and blood cancers. We focused on outcomes such as laboratory turnaround times, the interval from sample collection to testing, and the time from diagnosis to starting treatment. Overall, reflex testing consistently reduced delays in the cancer care pathway. In non-small-cell lung cancer, for example, turnaround times decreased by 1–38 days, testing initiation was faster by 13–29 days, and time to treatment fell by 1–44 days. These improvements were associated with a 10–47% increase in patients receiving first-line treatments guided by biomarkers. Reflex testing also increased test uptake by 7–50% and reduced test failures by 10–14%. The size of these benefits varied depending on the type of cancer, the biomarkers tested, and how reflex testing was implemented. In conclusion, reflex biomarker testing can make cancer diagnosis and treatment more efficient and increase the use of targeted therapies. However, its impact depends on the specific cancer, biomarker, and local resources, highlighting the need for tailored approaches and careful evaluation of costs and clinical benefits.