Biomarker testing: The gap between guidelines and what actually happens in the clinic
Industry Buzz
The biggest barrier to testing is insurance coverage. Not every insurance routinely covers testing, and some only cover testing on tissue and not on blood. So knowing what insurances will and won't cover helps with solving this problem.
—Daniel Landau, MD
Comprehensive molecular profiling is resource-intensive, and results are only as good as the sample quality, which can be compromised by staining artifacts or degradation. There's also an underappreciated issue of sampling error.
—Young Kwang Chae, MD
Precision oncology depends on biomarker testing. Guidelines now recommend broad molecular profiling across multiple tumor types.[]
Oncologists are showing enthusiasm for how the recent FDA decisions are shaping treatment sequencing, biomarker testing, or patient selection in their everyday practice.
In an exclusive interview with MDLinx, three oncologists shared their perspectives. Their observations highlight both the advances obtained as well as the barriers to implementation.
Board-certified oncologist Sagar Lonial, MD, Professor and Chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine and member of the International Myeloma Foundation’s Scientific Advisory Board, states, “I think that having access to methods to sequence BCMA and GPRC5d is really critical if one is to consider re-treatment with agents directed at those targets. Furthermore, as we get to more genomic testing as a standard, we will learn much more about how to better sequence therapies or combine them to improve outcomes, especially among high-risk patients.”
It is probably no surprise that, in practice, testing rates remain inconsistent. The gap shows up across settings, payers, and disease stages.
Discussing some of the biggest barriers to guideline-recommended biomarker testing, Young Kwang Chae, MD, a medical oncologist and researcher specializing in personalized precision medicine and early-phase clinical trials at Northwestern University Feinberg School of Medicine, said, "The most persistent barriers are turnaround time, cost, and tissue adequacy.”
Related: Inside the shift: How oncologists are using AI for trial matchingTurnaround time
In advanced disease, clinicians often start therapy before full molecular results are in. When asked how often this happens, Daniel Landau, MD, board-certified oncologist and hematologist and an expert contributor at The Mesothelioma Center in Orlando, said, “Often, testing helps to tweak and tailor therapy, but the backbone of therapy may remain the same. In these settings, we sometimes start chemotherapy first and then tweak based on results—results can take 2-3 weeks to come back sometimes!”
Next-generation sequencing panels often require 10 to 21 days in routine practice. A 2024 community hospital study in Canada among patients with NSCLC cited benchmarks of 10 working days after sample receipt (College of American Pathologists guidelines) and 14 calendar days ( Ontario Lung Cancer Tissue Pathway). In the study, 79.7% of patients still did not have core biomarker results available at the time of medical oncology consultation.[]
Dr. Landau noted, “I have come across cases where testing took longer than expected, and I used therapies that I wouldn't have picked otherwise.”
Liquid biopsy offers faster turnaround, but sensitivity varies by tumor burden and shedding.[]
Tissue access and sample adequacy
Insufficient tissue remains a frequent issue. Small biopsies, especially in lung cancer, limit the ability to run broad panels.
When asked if tissue limitations or sample quality impact the ability to order comprehensive panels, Dr. Landau said, “Yes, absolutely. Sometimes, testing on blood doesn't detect sufficient tumor DNA. Sometimes we can't get enough tissue. So we may have to try both."
Dr. Chae adds, “Comprehensive molecular profiling is resource-intensive, and results are only as good as the sample quality, which can be compromised by staining artifacts or degradation. There's also an underappreciated issue of sampling error: a single biopsy may not capture the full biological complexity of a heterogeneous tumor, meaning we may be making treatment decisions based on an incomplete picture.”
A report among patients with NSCLC found that up to 43% had insufficient tissue for genotyping; the reasons included biopsy not being able to be performed safely, limited sampling, or inability to obtain adequate tissue.[]Interventional radiology capacity and procedural risk add another layer. In frail patients, repeat biopsy is not always feasible.
Insurance coverage remains a barrier
Dr. Landau acknowledges the insurance hurdle: “The biggest barrier to testing is insurance coverage. Not every insurance routinely covers testing, and some only cover testing on tissue and not on blood. So knowing what insurances will and won't cover helps with solving this problem.”
While Medicare expanded coverage for next-generation sequencing in advanced cancers, private payer policies remain inconsistent.[]Out-of-pocket costs influence ordering behavior. In some community settings, clinicians still default to single-gene assays due to cost concerns or prior authorization delays.
In a multi-study review of biomarker testing adoption, lack of insurance coverage ranked as one of the top two barriers cited by oncologists when deciding whether to order next-generation sequencing.[]
A separate scoping review found financial constraints and inadequate reimbursement reported in 71% of studies evaluating barriers to biomarker testing implementation.[]
Workflow fragmentation
Community oncology faces the largest gap. Most U.S. cancer care occurs outside academic centers. These settings face staffing limits, lower access to in-house molecular pathology, and less exposure to rapidly evolving biomarker panels.
Plus, testing requires coordination across oncology, pathology, and external labs. Breakdowns occur at multiple points. Orders are not placed. Samples are not sent. Results are not integrated into the EHR in a usable format.
A national survey of oncologists found that time constraints, limited resources, and difficulty obtaining adequate tissue were common reasons for not ordering biomarker testing.[] Additional studies highlight insurance barriers and lack of decision support as ongoing contributors.
However, digital tools are starting to address this. EHR-integrated prompts, radiomics, and AI-driven test selection systems aim to standardize ordering. Dr. Chae said, “Expanding how we think about biomarkers — to include imaging-derived features alongside molecular data — offers a path to capturing more comprehensive, actionable information earlier in the care pathway."
The idea is to use CT, MRI, and PET more quantitatively, capturing features such as tumor heterogeneity, vascular complexity, and metabolic activity. This approach could supplement molecular testing, give a broader view of the disease biology, and predict response to immunotherapy. Early data suggest improved adherence, though adoption remains uneven.
In conclusion, the gap between guidelines and practice persists despite clear clinical benefit, driven by operational barriers.
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