Biomarker testing is essential for clinical care in non-small cell lung cancer (NSCLC), and integrating it into standardized workflows is critical for biomarker-informed treatment decisions. LUNGevity’s Value Proposition Working Group, which includes over 20 biopharma, diagnostic, professional societies, and patient advocacy organizations, has identified key resources and the latest research supporting the use of broad molecular panels, typically next-generation sequencing (NGS), in NSCLC.
This information equips hospital and healthcare leadership, as well as payers, to effectively communicate the clinical value of biomarker testing in improving patient outcomes and drive broader organizational commitment to its implementation or coverage.
This page is updated quarterly with new studies. Older studies are archived here.
Advancing Patient Care Through Biomarker Testing in NSCLC
Applying precision medicine solutions at an institutional level leads to the best possible patient outcomes by ensuring that each patient receives the right treatment at the right time. Precision medicine and biomarker testing implemented at diagnosis can equip oncology providers with the data necessary to personalize patient care and help patients avoid treatments that are unlikely to work, exposing them to unwanted toxicity.
Evolving clinical guidelines for many solid tumors recommend that when feasible, testing be performed via a broad, multi-gene next-generation sequencing (NGS) tests to support physicians in identifying therapies and clinical trial options specific to each individual patient and their disease. Broad or comprehensive NGS testing, also referred to as molecular testing, comprehensive biomarker testing, genomic profiling, and genotyping, simultaneously assesses tissue or blood samples for all potentially actionable genomic variants (biomarkers) in a single test.
Clinical Guidelines on Biomarker Testing
Ensure your institution is providing state-of-the-art cancer care that aligns with evolving nationally recommended guidelines*:
- National Comprehensive Cancer Network® (NCCN®) NSCLC Guidelines
- American Society of Clinical Oncology (ASCO) Guidelines
- Association for Molecular Pathology (AMP) / College of American Pathologists (CAP) / International Association for the Study of Lung Cancer (IASLC) Guidelines
*Clinical guidelines may require account credentials to access.
Supportive Statements from Professional Societies
- Read through supportive research here
Molecular Biomarker Testing Patterns and Turnaround Time in US Patients With Advanced Non–Small Cell Lung CancerWang, et al., JNCCN. 2025
A real-world EHR derived US cohort analysis (N = 33,945) shows that molecular biomarker testing rates for advanced non–small cell lung cancer (aNSCLC) have steadily increased from 2011 to 2023. Despite this progress, the average turnaround time for biomarker results has converged near three weeks, which is longer than the recommended benchmark of two weeks for critical biomarkers like ALK and EGFR.
When turnaround times exceed two weeks, patients with EGFR or ALK alterations (n = 4,020) are much more likely to receive non-targeted first-line therapies -- almost twice the odds for each additional week of delay. Due to extended turnaround time, 12% of patients (498 out of 4,020) began early nontargeted treatment before results were available. This early initiation of non-targeted treatment is associated with significantly worse real-world progression-free survival (9 months vs. 11 months for those who receive targeted therapy based on timely results).
These findings emphasize that delays in NGS testing not only reduce the likelihood of patients receiving the most optimal, personalized treatments, but may also directly impact clinical outcomes. All testing results should be obtained before starting treatment . Streamlining workflows to meet the ≤2-week benchmark for biomarker testing is essential to ensure that first-line therapy decisions are informed by molecular testing results, ultimately improving care for aNSCLC patients.
Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort
Iams, et al., JAMA Network Open. 2024
In this study, the authors evaluated whether the use of both tumor tissue and circulating tumor DNA (ctDNA) genomic profiling increased detection of guideline-based actionable mutations compared to tissue testing alone. The analysis examined a cohort of 3,209 patients with stage IV solid tumors across four cancer types, including non-small cell lung cancer (NSCLC). Overall, 45.1% of patients had at least one actionable variant identified through either testing method.
In patients with NSCLC with actionable mutations,- 65.7% of mutations were identified by both tests
- 29% were detected only through tissue profiling
- 5.5% of mutations were exclusively identified by ctDNA despite successful tissue profiling
These findings suggest that combining tissue profiling and ctDNA identifies more patients eligible for targeted therapies than either method alone, providing support for the integration of both approaches to optimize molecularly guided treatment decisions in advanced cancers.
Real-World Impact of Comprehensive Genomic Profiling on Biomarker Detection, Receipt of Therapy, and Clinical Outcomes in Advanced Non–Small Cell Lung Cancer
Law JW, et al. JCO Precision Oncol. 2024
This retrospective study included 3,884 patients with advanced NSCLC diagnosed between 2011 and 2023. Of these, 20% received comprehensive genomic profiling (CGP) and 80% received only single-gene testing. CGP identified one or more actionable biomarkers in 32% of patients, compared to 14% with single-gene testing. Patients who received CGP were also more likely to receive matched targeted therapy and had improved overall survival; among treated patients with actionable results, matched therapy was associated with longer median real-world overall survival (rwOS): 34 months vs 14 months for CGP, and 27 months vs 10 months for single-gene testing.
Comprehensive genomic profiling doubled the detection of actionable biomarkers compared to single-gene testing and was associated with higher matched therapy use and significantly longer survival, supporting its clinical value in managing advanced NSCLC.
Association between availability of molecular genotyping results and overall survival in patients with advanced nonsquamous non-small-cell lung cancer
Aggarwal C, et al. JCO Precis Oncol. 2023
In this real-world cohort study, the authors examined electronic health records of 326 patients with newly diagnosed metastatic nonsquamous NSCLC to determine the association between the availability of biomarker testing before initiating therapy and overall survival.
At a 14.2-month median follow-up, patients with biomarker testing results available prior to first-line therapy had significantly longer overall survival rates than patients who did not have results available.
Association of timely comprehensive genomic profiling with precision oncology treatment use and patient outcomes in advanced non-small-cell lung cancer
Yorio J, et al. JCO Precis Oncol. 2024
Despite improved insurance coverage since 2018, comprehensive biomarker testing remains substantially underutilized.
In this real-world, electronic health record study, the authors examined the implications of timely comprehensive biomarker testing on quality-of-care for patients with advanced NSCLC.
Use of profiling results to inform first-line therapy choice was associated with increased use of matched targeted therapies, translating into longer time to therapy discontinuation and avoidance of costly treatments that are unlikely to be effective.
Providing Accessible and Equitable Biomarker Testing for NSCLC
Implementing precision medicine will enhance accessibility and equity to testing and appropriate treatments for all patients. Comprehensive biomarker testing for all patients with NSCLC can help to reduce existing disparities in care and improve clinical outcomes, quality of care, and patient satisfaction.
A precision medicine approach can be customized to fit your patients, care teams, and framework, with solutions that align with existing workflows and show immediate positive impact.
- Read through supportive research here
- Strategies for Addressing Gaps in Biomarker Testing Patient Drop Off
Tsimberidou, et al., JCO. 2024
Despite proven benefits of biomarker-driven therapies, two-thirds of eligible patients did not receive appropriate precision oncology treatments due to lack of biopsy referral, insufficient tissue quality, delays in test ordering and reporting, misinterpretation of results, and limited access to targeted therapies. Closing these gaps is essential to improve clinical outcomes, equity, and health system efficiency. In this review article, authors analyzed published data to describe gaps in steps along the precision oncology pathway.
- Seven critical gaps: Each step in the pathway, from tumor biopsy referral, biospecimen collection, evaluation of biospecimens, biomarker test ordering, biomarker test performance, test result reporting, and treatment selection had measurable attrition. Biomarker test ordering (18.1%) and the treatment decision (29.2%) were two of the larger contributors.
- Solutions proposed:
- Standardize biopsy and biospecimen handling (CAP guidelines).
- Implement multiplex NGS testing and harmonize clinical guidelines.
- Improve lab quality control and turnaround times.
- Integrate biomarker data into EHRs and enhance clinical decision support systems.
- Ensure equitable access and payer coverage for testing and targeted therapies.
- Call to action: Multistakeholder collaboration (clinicians, labs, payers, policymakers) is needed to translate scientific advances into routine clinical practice.
Personalized medicine in oncology is relies on practice gap alleviation and systemic reforms and consistent implementation strategies are critical.
Real World Analysis of Disparities in Biomarker Testing and Use of Recommended Targeted Therapies in Metastatic NSCLC in the US
Dennis, et al., JCO Precis Oncol. 2025
Data from over 42,000 patients, between 2011 and 2023, shows that biomarker testing has improved in the United States. More targeted therapies are being used (especially EGFR and ALK), and patients who were tested for biomarkers were more likely to receive therapies that matched their cancer’s genetic profile. While over 82% of patients received at least one biomarker test by 2023, some are single biomarker tests, some are multi-gene panels, and some are NGS.
However, disparities still exist today and are prevalent in the following groups:
- Race (Asian patients had the highest testing rate at over 91% and black patients were tested the least often.)
- Insurance type (Patients with commercial insurance were tested more often than those with Medicare and Medicaid.)
- Smoking history (Patients who never smoked were more likely to be tested than those with a history of smoking.)
- Cancer type (Patients with nonsquamous cell carcinoma were tested more frequently than those with squamous cell carcinoma.)
- Age and Gender (Younger patients and women are more likely to be tested.)
- Practice type (Patients treated at academic centers are more likely to receive biomarker-informed therapies than those at community clinics.)
Despite major improvements in biomarker testing and access to life-extending targeted therapies for metastatic NSCLC, significant disparities persist— who gets tested and treated still depends too much on demographic factors rather than just medical need.
Healthcare disparities, screening, and molecular testing in the changing landscape of non–small cell lung cancer in the United States: a review
Kurzrock R, et al. Cancer Metastasis Rev. 2024
In this review article, the authors describe the disparities that exist across lung cancer screening, diagnosis, and treatment regimens; impact on incidence and survival; and demographic variances. Several strategies to reduce lung cancer health disparities are reviewed including improving screening rates, increasing clinical trial diversity, and implementing standardized molecular testing policies.
Solutions are presented to address potential difficulties that may be encountered in establishing biomarker testing programs, and include:
- Strategic use of liquid biopsy testing (cfDNA)
- Increased education opportunities for physicians to stay abreast of rapidly evolving practice standards and treatments
- Identification and support of a champion physician to educate healthcare teams
- Inclusion of nurse navigators to facilitate communication within care teams and support patient education
- Collaboration with patient advocacy organizations to disseminate information
- Familiarization with CMS coverage determinations on next-generation sequencing (NGS) as a diagnostic tool
- Support participation of underserved populations in clinical trials
Disparities in biomarker testing and clinical trial enrollment among patients with lung, breast, or colorectal cancers in the United States
Bruno DS, et al. JCO Precis Oncol. 2022
In this study, the authors examined racial differences in biomarker testing and clinical trial participation in the United States among patients with advanced/metastatic NSCLC, colorectal cancer, or breast cancer.
Among nearly 15,000 patients with NSCLC, Black patients were significantly less likely than White patients to receive NGS testing at any time (39.8% vs 50.1%) or to be treated in a clinical trial (1.9% vs 3.9%).
As NGS testing for patients with advanced NSCLC is fundamental to determining effective therapies, this study underscores the substantial disparity in equitable access to appropriate care.
Racial and ethnic inequities at the practice and physician levels in timely next-generation sequencing for patients with advanced non–small-cell lung cancer treated in the US community setting
Vidal GA, et al. JCO Oncol Pract. 2024
In this study, the authors examined racial and ethnic disparities in rates of NGS for patients with advanced NSCLC in a community setting to inform policies to improve equitable quality of care. They reported that among ~12,000 patients with advanced NSCLC, non-Latinx Black and Latinx patients were consistently underserved, with ~8% lower rate of NGS testing versus non-Latinx White.
Based on these findings, there is a health equity barrier in biomarker testing, with Latinx (and potentially other minorities) being underrepresented in biomarker testing compared to non-Latinx White individuals.
Operational Improvements to Optimize Patient Care
Use of precision medicine can drive substantial cost savings for your organization by enabling more effective treatments, reducing unnecessary interventions, and improving patient outcomes.
Integrating timely use of comprehensive biomarker testing, employing standardized and streamlined clinical workflows such as "reflex" biomarker testing, and establishing support infrastructure across relevant cancers, can help reduce patient time to treatment. Additional efficiencies and improvements in outcomes can be found from better educating physicians in precision medicine and facilitating precision-medicine enabled multidisciplinary treatment approaches.
Interpreting CMS Rules: Quick Reference Tools
Comprehensive Genomic Testing for Lung Cancer Patients: Pathologist-Driven Solutions: Summary of the May 2024 MolDx clarification of CMS policy for pathologist-initiated biomarker testing
Medicare Policy for Genomic Test Orders: Resources that Describe CMS Policy: A companion resource with detailed background and insights on Medicare policy for diagnostic test orders
Understanding Medicare’s Lab Test Billing Rules: Inpatients, Outpatients, and the 14-Day Rule: Simple explainer on how to interpret the 14 day rule for providers, billing staff, and administrators. Last updated June 2, 2025
- Read through supportive research here
- Developing Consensus for a More Provider-Friendly Next-Generation Sequencing Molecular Biomarker Report
Gibson, et al., The Journal of Molecular Diagnostics. 2025
Currently, reports containing complex molecular biomarker results are often lengthy, inconsistent, and may be hard to interpret, which may lead to inefficiencies and underutilization of testing information and connecting it with treatment decisions. This article discusses the efforts of the Association for Molecular Pathology to examine best practices of and challenges with current reports to develop a template to optimally present biomarker results to oncologists, pathologists, and other healthcare providers, as well as patients. The developed template recommends:
- Standardizing nomenclature: Use consistent terminology, such as HGVS and HUGO standards, to describe genetic variants.
- Using tiered classification for variants: Use AMP/ASCO/CAP guidelines to categorize variants by their clinical significance.
- Clear communication of variant significance: Clearly state the relevance of each variant to diagnosis, prognosis, and therapy.
- Therapeutic implications and evidence levels: Include information about how each biomarker may impact treatment choices, supported by evidence.
- Providing essential report elements: Incorporate patient demographics, specimen details, assay description, biomarker results table, interpretation, pertinent negatives, and the therapeutic/diagnostic/prognostic significance.
- Using a provider-friendly format: Design the report to be concise, consistent, and easy for oncologists and other healthcare providers to interpret.
- Supporting evidence-based decisions: Ensure the report helps providers make accurate, evidence-based treatment decisions and reduces the risk of errors.
Adopting standardized, provider-friendly templates is critical for precision oncology, as it improves interpretation, reduces errors, and supports evidence-based treatment decisions. The next step is to ensure these templates and mock reports are widely available to all providers, ideally as free downloads, and to encourage consistent implementation across institutions.
Programmatic Efforts Increase Adoption of Genomic Precision Medicine in Cancer Care in a Community Cancer Center
Darabi et al., JCO Precis Oncol. 2022
This research demonstrates that coordinated, programmatic initiatives in community cancer centers can significantly boost the adoption and clinical impact of genomic precision medicine, ultimately improving patient care.
A multidisciplinary team implemented a coordinated program to support the interpretation of genomic data, educate clinicians, and improve the use of somatic and germline genetic testing in cancer care to overcome barriers in adopting precision medicine, such as lack of clinician understanding, slow turnaround times, and insufficient DNA samples.
The most successful efforts included:
- Increased reflex testing protocols (from 661 in year one to 1532 in year three)
- In-house curation of genomic reports (provided deeper analysis beyond commercial lab reports and resulting in additional treatment or trial recommendations in 42.9% of cases)
- Educational seminars and tumor boards (increased physician understanding and confidence)
- Consultation services (requests for interpreting complex genomic data increased by 107.5%, indicating growing reliance and trust in precision medicine
Biomarker Testing Approaches, Treatment Selection, and Cost of Care Among Adults With Advanced Cancer
DaCosta Byfield et al., JAMA Network Open. 2025
Expanding CGP access, addressing testing gaps, educating providers and payers and monitoring and reporting testing trends will all have real-world advantages for both the patient and the payer.
A study of a large national claims database examined 1) how 26,311 adults with newly diagnosed advanced cancers (breast, colorectal, gastric, non-small cell lung, ovarian, and pancreatic) received biomarker testing and 2) how this testing affected healthcare costs.
Overall results show:
- Testing Rates Are Low but Improving (Although rates increased from 32% in 2018 to 39% in 2021-2022, only 35% of patients received molecular testing.)
- Cost Neutrality of CGP Testing (no significant increase in per-patient, per month costs for CGP vs. non-CGP testing across all cancer types, suggesting CGP can improve treatment precision without raising costs)
- Clinical Relevance (Despite growing insurance coverage and guideline support, many patients still miss out on potentially life-extending targeted therapies due to lack of testing.)
Impact of Next-Generation Sequencing vs Polymerase Chain Reaction Testing on Payer Costs and Clinical Outcomes Throughout the Treatment Journeys of Patients with Metastatic Non-Small Cell Lung Cancer
Bestvina CM, et al. J Manag Care Spec Pharm. 2024
In this study, the authors used a Markov model to compare next-generation sequencing (NGS) and polymerase chain reaction (PCR) biomarker testing in patients with newly diagnosed metastatic non–small cell lung cancer (NSCLC) from a US payer’s perspective. The model assessed costs and clinical outcomes for each testing strategy over three years.
Based on a modeled population of 100 patients (75% commercial and 25% Medicare),
- NGS identified more actionable mutations than PCR (45.9% vs 40.0%), leading to more patients receiving appropriate targeted therapy
- NGS resulted in cost savings compared to PCR with $7,386 savings per patient at 1 year, $4,060 at 2 years, and $1,092 at 3 years. These savings were primarily due to fewer missed mutations and lower costs from delayed or inappropriate therapy
- Patients receiving targeted therapy had longer progression-free and overall survival rates than those who received inappropriate non-targeted therapy
The study authors concluded that NGS testing improves both clinical outcomes and cost efficiency compared to PCR, supporting broader adoption of NGS in metastatic NSCLC management.
Widespread Adoption of Precision Anticancer Therapies After Implementation of Pathologist-Directed Comprehensive Genomic Profiling Across a Large US Health System
Dowdell AK, et al. JCO Oncol Pract. 2024
In this study, the authors explored the impact of a pathologist-requested comprehensive genomic profiling (CGP) protocol on treatment selection and outcomes in 3,216 patients with advanced cancer across a large US health system. Utilizing a 523-gene panel at diagnosis, the protocol identified actionable biomarkers in 49% of patients. Compared to legacy 50-gene panels, CGP increased actionable mutation detection rates from 33% to 67%. Patients treated with biomarker-guided therapies demonstrated superior overall survival compared to those receiving chemotherapy alone (25 months vs 17 months).
The authors concluded that pathologist-directed CGP at diagnosis leads to broader adoption of precision therapies and improved patient outcomes, supporting a shift away from conventional chemotherapy as standard practice in advanced cancer care.
Electronic medical record–based nudge intervention to increase comprehensive molecular genotyping in patients with metastatic non–small cell lung cancer: results from a prospective clinical trial
Marmarelis ME, et al. JCO Oncol Pract. 2024
In this publication, the authors describe how they designed, implemented, and assessed performance of an electronic medical record (EMR)-based “nudge intervention” to prompt plasma-based molecular testing (ie, liquid biopsy) at the time of initial medical oncology consultation for patients with newly diagnosis NSCLC.
Across three practice sites in a large health system, the EMR “nudge intervention” lead to a significantly higher percentage of patients who received concurrent plasma and tissue comprehensive biomarker testing at diagnosis (68.4% before the EMR nudge integration to 93.6% following the nudge) and guideline-concordant care (78.2% before the EMR nudge integration to 89.8% following the nudge).