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
Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer CohortIn 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 CancerThis 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
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.
Biomarker testing, treatment, and outcomes in patients with advanced/metastatic non-small cell lung cancer using a real-world database
In this study, the authors compared overall survival rates by biomarker testing status and by receipt of guideline-recommended therapy in a large cohort of US patients with advanced or metastatic NSCLC. Despite recommendations from nationally recognized clinical guidelines, the overall rate of testing for actionable biomarkers was low. Of 21,572 patients studied, only 69% received testing for at least 1 actionable biomarker prior to or on initiation of first-line treatment, demonstrating opportunity for improvement.
Patients who received front-line biomarker testing and appropriate guideline-recommended therapy experienced significant improvements in overall survival rates compared with those who never received biomarker testing.
Association of timely comprehensive genomic profiling with precision oncology treatment use and patient outcomes in advanced non-small-cell lung cancer
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.
References
- Aggarwal C, et al. Association Between Availability of Molecular Genotyping Results and Overall Survival in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer. JCO Precis Oncol. 2023 Jul;7:e2300191. doi: 10.1200/PO.23.00191.
- Bhandari NR, et al. Biomarker testing, treatment, and outcomes in patients with advanced/metastatic non-small cell lung cancer using a real-world database. J Natl Compr Canc Netw. 2023 Sep;21(9):934-944.e1. doi: 10.60 04/jnccn.2023.7039.
- Hofmarcher T, et al. A global analysis of the value of precision medicine in oncology – The case of non-small cell lung cancer. Front Med (Lausanne). 2023 Feb 20:10:1119506. doi: 10.3389/fmed.2023.1119506.
- Schwartzberg L, et al. Improving biomarker testing in advanced non-small-cell lung cancer and metastatic colorectal cancer: experience from a large community oncology network in the USA. Future Oncol. 2023 Jun;19(20):1397-1414. doi: 10.2217/fon-2022-1216.
- Yorio J, et al. Association of timely comprehensive genomic profiling with precision oncology treatment use and patient outcomes in advanced non-small-cell lung cancer. JCO Precis Oncol. 2024 Mar;8:e2300292. doi: 10.1200/PO.23.00292.
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
Healthcare disparities, screening, and molecular testing in the changing landscape of non–small cell lung cancer in the United States: a review
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
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
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.
References
- Kurzrock R, et al. Healthcare disparities, screening, and molecular testing in the changing landscape of non–small cell lung cancer in the United States: a review. Cancer Metastasis Rev. 2024 May 16. doi: 10.1007/s10555-024-10187-6. Online ahead of print.
- Bruno DS, et al. Disparities in Biomarker Testing and Clinical Trial Enrollment Among Patients With Lung, Breast, or Colorectal Cancers in the United States. JCO Precis Oncol. 2022 Jun:6:e2100427. doi: 10.1200/PO.21.00427.
- Vidal GA, et al. 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. JCO Oncol Pract. 2024 Mar;20(3):370-377. doi: 10.1200/OP.23.00253. Epub 2024 Jan 9.
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
- 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
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 SystemIn 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
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).
Interpreting and integrating genomic tests results in clinical cancer care: overview and practical guidance
In this review publication, the authors provide a primer on the use of precision medicine and opportunities for enhanced treatment through next-generation sequencing (NGS) testing in oncology. They assert that a lack of understanding of the clinical utility of NGS and difficulty of results interpretation by practicing oncologists result in decreased use of precision medicine in routine cancer care.
The authors present practical guidance for interpreting genomic test results to help inform clinical decision-making and discuss potential challenges to wider implementation of precision medicine into routine care.
Pathologist-initiated reflex testing for biomarkers in non-small-cell lung cancer: expert consensus on the rationale and considerations for implementation
In this publication, the authors provide an expert consensus review of the importance of implementing reflex testing in NSCLC, in which the responsibility for comprehensive molecular testing for an agreed range of biomarkers lies with the pathologist versus the treating oncologist.
The study’s authors demonstrate how reflex testing has been shown to standardize and expedite the process of ordering biomarker tests to ensure more patients are tested and provide considerations for defining reflex testing protocol, engaging with institutional stakeholders, and defining roles and responsibilities within the multi-disciplinary care team.
Total cost of testing for genomic alterations associated with next-generation sequencing versus polymerase chain reaction testing strategies among patients with metastatic non-small cell lung cancer
In this study, researchers aimed to assess the total cost associated with next-generation sequencing versus polymerase chain reaction (PCR) testing strategies, which often involve analyzing single or pre-selected biomarkers that may not align with clinical guideline recommendations, among patients with metastatic NSCLC from a Medicare and Commercial payer perspective. Analysis was based on a hypothetical plan of 1 million patients insured through a blend of Medicare and commercial health plans.
NGS was associated with a shorter estimated mean time to initiation of appropriate targeted therapy compared to all other PCR strategies and resulted in the lowest per patient total cost of testing, demonstrating the clinical and economic value of adopting NGS for patients with metastatic NSCLC.
References
- Anand K, et al. Clinical Utility of Reflex Ordered Testing for Molecular Biomarkers in Lung Adenocarcinoma. Clin Lung Cancer. 2020 Sep;21(5):437-442. doi: 10.1016/j.cllc.2020.05.007. Epub 2020 May 13.
- Casolino R, et al. Interpreting and integrating genomic tests results in clinical cancer care: Overview and practical guidance. CA Cancer J Clin. 2024 May-Jun;74(3):264-285. doi: 10.3322/caac.21825. Epub 2024 Jan 4.
- Gosney JR, et al. Pathologist-initiated reflex testing for biomarkers in non-small-cell lung cancer: expert consensus on the rationale and considerations for implementation. ESMO Open. 2023 Aug;8(4):101587. doi: 10.1016/j.esmoop.2023.101587. Epub 2023 Jun 23.
- Marmarelis ME, et al. 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. JCO Oncol Pract. 2024 Jul 3:OP2400070. doi: 10.1200/OP.24.00070. Online ahead of print.
- Vanderpoel J, et al. Total cost of testing for genomic alterations associated with next-generation sequencing versus polymerase chain reaction testing strategies among patients with metastatic non-small cell lung cancer. J Med Econ. 2022 Jan-Dec;25(1):457-468. doi: 10.1080/13696998.2022.2053403
- Waterhouse DM, et al. Closing the testing gap: Standardization of comprehensive biomarker testing for metastatic non-small-cell lung cancer in a large community oncology practice. JCO Oncol Pract. 2023 Jun;19(6):e951-e956. doi: 10.1200/OP.22.00817. Epub 2023 May 1.