Adopting Reflex Biomarker Testing to Improve Clinical Workflows for Patients With Non–Small Cell Lung Cancer

Key Takeaways:

• Biomarker testing should occur at time of biopsy: For patients newly diagnosed with non–small cell lung cancer (NSCLC), biomarker testing should be ordered as early as possible to reduce delays in treatment decisions, which could improve patient outcomes.
• Reflex biomarker testing streamlines clinical workflows: Ordering biomarker testing close to biopsy shortens the time between test results and treatment planning and avoids the possibility of patients beginning an ineffective therapy.
• Coverage for broad panel testing could improve with national evidence-based endorsements: National Comprehensive Cancer Network (NCCN) guidelines should recommend broad biomarker testing for every patient with NSCLC and demonstrate the clinical harm that is associated with delayed or no testing.

Nikki Martin, MA, senior director of Precision Medicine Initiatives at LUNGevity, discusses findings from the study “Standardized Protocols for Reflexing to a Multigene Panel for Patients With Non–Small Cell Lung Cancer: Prevalence and Perceived Barriers to Comprehensive, Pathologist-Ordered Biomarker Reflex Testing,” which examines the challenges to widespread adoption of biomarker testing among patients with NSCLC. Martin shares insights on the importance of reflex biomarker testing, emphasizing a shift toward routine comprehensive diagnostic workflows.

Nikki Martin, MA: My name is Nikki Martin, and I serve as the senior director of Precision Medicine Initiatives at the LUNGevity Foundation. My work focuses on supporting lung cancer patients’ access to comprehensive biomarker testing and helping ensure that those results can be used to identify appropriate matched therapies and clinical trials.

Before joining LUNGevity, I held patient advocacy and public affairs roles at Genentech and Novartis. At Novartis, I worked with the diagnostics business, which gave me a firsthand understanding of the complexity of diagnostics and some of the challenges companies face in navigating reimbursement for new diagnostic innovations.

Together, those experiences gave me a perspective that spans patient advocacy, precision medicine, diagnostics, and the health care system—and how all those pieces need to work together to get the right information to patients at the right time.

What does an ideal biomarker testing pathway for a patient newly diagnosed with NSCLC look like, and how far is current practice from that ideal?

Martin: Biomarkers are foundational to cancer diagnosis and treatment planning. Ideally, that information should be available to the patient and oncologist when they are making the treatment decision.

For a patient newly diagnosed with NSCLC, an ideal biomarker testing pathway would start with testing being ordered at the time of biopsy or as soon as the histologic diagnosis is established. There are many ways to build that workflow, and it should be coordinated around the needs of the local practice. For example, some sites may have the pathologist order the broad biomarker panel, while others may have the pulmonologist place the order. Another approach could be a standing order under an oncologist’s name that allows the pathologist to initiate testing. Some sites have nurses review the daily NSCLC diagnoses coming out of the lab and place the orders based on that list.

There is not one “best” model. This flexibility allows health systems to develop workflows that fit their local needs and provider preferences. What is important is that biomarker testing happens early and reliably, without creating an unnecessary delay between diagnosis and treatment planning.

The study “Turnaround Time of Biomarker Testing in Lung Cancer and Other Solid Tumors,” published in June 2026 in JCO Oncology Practice by Fox and colleagues found that it takes an average of 4 weeks for biomarker testing results to get back to the provider and patient. But the study also identified an important opportunity for improvement: there was an average 14-day delay between the biopsy and the placement of the biomarker testing order.

That is where reflexive testing workflows can really make a difference. If the testing order can be initiated automatically or as close to the time of biopsy or diagnosis as possible, we can eliminate that avoidable delay and move closer to the goal of having biomarker results available when the patient and oncologist are ready to make a treatment decision.

What are the clinical and operational advantages of pathologist-initiated reflex testing as opposed to waiting for an oncologist’s order?

Martin: The clinical benefits are clear. What’s most important is that patients can get to the appropriate therapy or clinical trial sooner. We know that time matters for patients with cancer, so getting someone to the right treatment 3 weeks, 2 weeks, even 1 week sooner can improve outcomes. There’s also compelling evidence that the consequences of failing to identify actionable biomarkers can be substantial.

There is also a significant emotional benefit for patients and their families. When biomarker results take weeks to come back, there can be a tremendous amount of anxiety and pressure to start treatment as quickly as possible. In some cases, patients may be started on chemotherapy or immunotherapy while the care team is still waiting for the complete biomarker results. That can be problematic because the full biomarker profile could identify a targeted therapy or clinical trial that would change the treatment approach. Having the results up front allows the patient and oncologist to make a more informed treatment decision from the beginning.

Reflex testing also helps make biomarker testing more consistent. When testing is standardized rather than dependent on an individual provider remembering to order it, every patient diagnosed at that site has the same opportunity to receive the appropriate testing. That consistency can help address inequities in care.

Research published by Kehl and colleagues in JAMA Network Open in 2024 identified differences in biomarker testing both between practices and within individual practices. This suggests that the setting where a patient receives care can influence whether and how quickly they receive biomarker testing. Standardizing the process, such as establishing who is responsible for ordering the test, when it should be ordered, and what testing should be performed, can help make care more equitable.

Operationally, the biggest benefit is efficiency. If biomarkers are part of a complete cancer diagnosis, particularly in lung cancer, then breaking the diagnostic process into 2 separate steps, separated by weeks and potentially involving different providers and specialties, doesn’t make much sense for a busy health system.

Instead, multidisciplinary teams can map out their workflow and determine who is responsible for each step. The goal is to make the process as seamless as possible, so that the biomarker order happens at the right time, the appropriate test is performed, and the results are available when the oncologist and patient are ready to make a treatment decision.

Some sites have taken this a step further by working with their regional payers. When payers understand that reflex testing is part of the established diagnostic workflow, they can become part of the solution rather than introducing another potential delay in the process.

It’s important to note that this isn’t a completely new concept. We have been doing this with breast cancer for decades. Once a pathologist confirms a breast cancer diagnosis, biomarker testing is routinely initiated as part of that diagnostic process. Lung cancer should move in the same direction.

Why does coverage remain challenging in early-stage disease, and what evidence would payers need to implement reimbursement for broader testing?

Martin: According to our study, providers cited coverage for broad panels as the top barrier to establishing a reflex testing workflow in lung cancer. Sites considering reflex workflows need to understand whether the tests they order will be covered and at what amount.

One reason coverage is challenging in early-stage NSCLC is that the current NCCN guidelines don’t yet recommend broad-based next-generation sequencing (NGS) for every patient with early-stage disease. The current guidelines recommend testing for specific biomarkers, including EGFR, ALK, and recently added RET, as well as PD-L1, because those results can affect treatment decisions given approved therapies available for each of those biomarkers. But broad panels should be part of an early lung cancer patient care regimen because clinical trials are a relevant treatment option, and a comprehensive panel is needed to identify those biomarkers.

Although the NCCN has not yet endorsed broad panels for patients with early-stage disease, they endorse clinical trials as part of a patient’s list of care options. Therefore, our goal is to gather data that will show guidelines committees and payers the clinical harm that occurs when patients are not tested for all biomarkers with possible therapies and clinical trials in early stage, to help close this gap in guidelines and medical policies.

In addition to NCCN guidelines, expanding the Medicare National Coverage Determination (NCD) to include testing for early-stage cancers will be a positive signal for payers that broad testing in early stage is clinically appropriate.

I’d like to note that pancreatic cancer guidelines became the first guideline for any cancer to have a strong recommendation for broad biomarker next-generation sequencing for all stages. We are hoping that we can use this example in pancreatic cancer to communicate the value to Medicare representatives and encourage them to mirror NCD policy, which then could have a positive impact on NCCN guidelines committees, and finally on commercial payers.

How should payers and providers balance the benefits of comprehensive upfront testing against concerns about unnecessary testing, particularly when not every result will ultimately affect treatment?

Martin: We need to look at this question from the perspective of the patient, rather than simply asking whether every individual test result will ultimately change treatment.

It’s true that not every biomarker we identify will be actionable for every patient. But the purpose of comprehensive upfront testing is to make sure we don’t miss the biomarker that could change a patient’s treatment. A comprehensive panel gives the oncologist the full picture of all the available treatment options, including clinical trials, at the point when treatment decisions are being made, rather than requiring multiple rounds of testing later.

We need to change the way the diagnosis is perceived and start to consider biomarker testing as part of the diagnosis process. Just like with an MRI that helps narrow the differential diagnosis and changes management whether the result is positive or negative, biomarker testing provides clinically actionable information that helps clarify the cancer diagnosis and inform the treatment approach.

There is also a cost to not testing. A recent study by Migliaccio-Walle and colleagues looked at the consequences of gaps in biomarker testing and precision-matched treatment for patients with metastatic NSCLC (mNSCLC). Among the patients modeled, nearly 49 500 were projected to have an actionable mutation. The study estimated that more than 19 000 people die a year, roughly the equivalent of a Boeing 747 crashing every other week, when broad biomarker testing is not ordered for mNSCLC patients.

This is a new study and illustrates an important point that the impact of missing actionable biomarkers can be substantial. LUNGevity is not alone in recognizing the essential nature of this testing for patient outcomes. The American Society of Clinical Oncology is field testing a national quality metric in lung cancer that would assess the percentage of mNSCLC patients getting appropriate testing and test-concordant treatment.

We should also consider the operational side. If you test narrowly upfront and then discover later that you need additional biomarkers, like most providers do now in early stage, you’re potentially ordering another test, obtaining another tissue sample, waiting for another result, and creating another decision point for the patient and care team. That can be more costly and inefficient than getting the appropriate comprehensive information upfront.

The goal should not be to test for everything indiscriminately. The goal should be to use evidence-based comprehensive testing that is appropriate for the cancer type and clinical setting and to build a workflow that gets those results back efficiently.

For NSCLC, where there are multiple actionable biomarkers and targeted therapies, the balance favors comprehensive upfront testing. We need to shift to a wider boundary lens, stop asking will this result change treatment, and instead ask whether we can afford to miss the result that could change treatment for this patient.