Strategies for improving biomarker testing rates in non-small cell lung cancer in north America: a scoping review

Introduction

Despite advances in treatment, lung cancer remains the second most common cancer in both men and women in the United States (U.S.) and Canada, and the leading cause of cancer-related deaths (1,2). An estimated 226,650,580 new cases of lung cancer will be diagnosed in 2025 in the U.S., with about 124,730 deaths from this disease (2,3). Over several decades, studies have solidified our understanding of non-small cell lung cancer (NSCLC) as a unique disease characterized by genetic and cellular diversity, leading to biomarker testing development (4-6). Clinical biomarker testing analyzes specific genetic mutations, protein expression, or other genomic alterations to inform treatment decisions for lung cancer patients (7). Biomarker identification has improved prognosis and enabled the development of therapeutic targets, including anti-programmed death-ligand 1 (PD-L1) immunotherapy (8-10).

In NSCLC, oncogenic driver mutations, cell signaling alterations, or tumor microenvironment changes are actionable therapy targets crucial in determining treatment choice (5,11). Biomarker test results inform NSCLC treatment by enabling biomarker-driven approaches aligned with precision medicine principles and clinical trial eligibility (12,13). Current National Comprehensive Cancer Network (NCCN) guidelines emphasize that all patients with advanced or metastatic NSCLC should undergo comprehensive molecular testing for biomarkers, including EGFR, ALK, ROS1, BRAF, NTRK1/2/3 fusions, MET, RET, and ERBB2. Additionally, upfront PD-L1 expression testing before first-line therapy is recommended to assess the utility of immune checkpoint inhibitors when no actionable mutations are found (11).

Although biomarker testing is imperative in lung cancer treatment, barriers include cost, time, sample quality, access, awareness, and increasing potential targets (14). This paper focuses on proposed solutions to address these barriers by assessing existing biomarker testing programs, revealing their challenges, and sharing successful strategies to assist healthcare providers. By fostering a deeper understanding of biomarker testing in lung cancer, this review aims to inform efforts to strengthen implementation and guide future research and clinical practice in this critical oncology area. We present this article in accordance with the PRISMA-ScR reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-761/rc) (15).

Methods

Study design and framework

We conducted a scoping review to identify strategies addressing common barriers to biomarker testing in lung cancer. We selected this methodology to broadly map available evidence, as recommended by Arksey and O’Malley (16), guided by the JBI Manual for Evidence Synthesis (17). This approach captured traditional research articles, consensus recommendations, and educational interventions, reflecting this evolving field’s multifaceted nature.

Search strategy

An academic health science librarian developed an electronic database strategy in consultation with the lead researchers. We used controlled-vocabulary subject headings and text words, including synonyms for lung cancer, precision medicine biomarkers, and provider education. These words were applied across titles, abstracts, and keywords using both subject headings and free-text strategies. An initial probe search was conducted on January 12, 2024, in Medline (Medline-ALL, Ovid). The results of that search were screened based on titles and abstracts by two reviewers independently, and the included peer-reviewed articles were used to refine the search strategy. Searches were conducted in the Medline, Embase (Elsevier), Cochrane Controlled Register of Trials (CENTRAL) (Wiley), CINAHL Plus with Full Text (Ebsco), and Scopus (Elsevier) databases, and the Web of Science between March and April 2024. Results were limited to human peer-reviewed articles from the U.S. and Canada.

The search strategy was adapted for other databases in part with the use of the Institute for Evidence-Based Healthcare’s Polyglot Search translator (18). For full search strategies, see Appendix 1. Records were managed using EndNote 21 and Covidence software.

Eligibility criteria

We included articles examining NSCLC in the U.S. and Canada published in English, involving adults (≥18 years old), addressing biomarker testing for clinical decision-making, and describing barriers or solutions to improve testing implementation. We excluded articles focused solely on clinical efficacy or diagnostic accuracy without addressing implementation issues.

Study selection and data extraction

Two independent reviewers screened titles and abstracts against inclusion criteria, with full-text reviews for potentially eligible articles. Discrepancies were resolved through discussion or a third reviewer. A standardized extraction form was developed and piloted. Extracted data underwent thematic synthesis to identify common barriers and key strategies.

Results

Database searching retrieved a total of 7,192 unique records, with 27 articles undergoing full-text screening; 14 articles were ultimately included. The screening history is presented in Figure 1, and the characteristics of included articles are summarized in Table 1. The selected articles represented empirical studies (n=9, 64%), qualitative studies (n=2, 14%), reviews and consensus/recommendation pieces (n=4, 29%), and opinion/editorial articles (n=2, 14%). Most originated from the U.S. (n=12, 86%), with the remainder from Canada (n=5, 36%). These articles spanned 2010–2024, reflecting evolving practices in biomarker testing. Analysis revealed three overarching themes: (I) operational challenges; (II) communication and knowledge gaps; and (III) access and financial constraints (Figure 2). A summary of barriers and corresponding solutions to biomarker testing is provided in Table 2.

Figure 1 This PRISMA flow diagram outlines the systematic review process, detailing the identification, screening, eligibility assessment, and inclusion of 14 studies from an initial pool of 7,192 records.

Figure 2 This conceptual framework organizes the barriers and solutions to biomarker testing into three domains: operational, communication and knowledge, and access and financial. Operational barriers, such as time constraints and insufficient tissue samples, can be addressed through advanced technologies, reflex testing, and standardized workflows. Communication and knowledge barriers, including coordination challenges, knowledge gaps, and the complexity of genomic medicine, are mitigated through multidisciplinary collaboration, provider education, and leveraging data. Access and financial barriers, like limited testing access and inadequate insurance coverage, require solutions such as funding infrastructure and improving reimbursement policies. This framework provides a structured approach to addressing the multifaceted challenges of biomarker testing. NGS, next-generation sequencing.

Operational barriers

Time-related constraints

Time-related constraints were reported in 85% (n=12) of articles as a barrier. These constraints stem from administrative burdens and lengthy processes for reporting and documenting results, detracting from patient time and affecting staff satisfaction (19,21,22,24). Physicians report that documenting biomarker testing is time-consuming (19). For example, some pulmonologists are required to collect adequate tumor tissue, stay informed about testing indications, and collaborate with oncologists and pathologists to ensure timely and appropriate testing (21).

Additionally, turnaround time remains a critical challenge in biomarker testing and can complicate the timely delivery of care (20,25,27,30-32). For instance, in advanced or metastatic NSCLC, the median turnaround time from diagnosis to the first biomarker result was 26 days for next-generation sequencing (NGS) compared with 15 days for other biomarker tests (30). Delays arise from missing pathology materials, obtaining external materials, pre-test discussions, and result complexity (25). Pathology laboratories often receive large volumes of tissue samples daily, which could lead to delays if samples intended for molecular profiling become mixed with the routine histology workload (26).

This issue compounds with substantial time investment for precision oncology tasks, including staying updated on advances, reviewing records, coordinating samples, determining trial eligibility, and resolving insurance issues (24). Extended standardized reporting times exacerbate delays in returning results to patients (20). The multi-step molecular testing process requires cross-department coordination, often causing delays that prevent timely targeted therapy (22,23). In some cases, providers start treatment before results are available, reflecting inconsistent adherence to clinical pathways and impacting outcomes (28,32).

Insufficient tissue samples

Insufficient tissue samples were reported in 74% (n=10) of articles as a barrier. Insufficient or poor-quality biopsy samples present a significant challenge for comprehensive biomarker testing, particularly in the context of NSCLC. The issue of inadequate tissue samples, whether due to limited material or suboptimal quality, impedes the ability to perform thorough biomarker analysis, which is crucial for targeted therapies and personalized treatment plans (20,24). For example, among 814 patients studied across 15 different sites throughout New Jersey and Maryland over a 2-year timespan, 53 had inadequate tissue for EGFR/ALK testing from their initial biopsy, representing 10% of the samples sent for analysis (23). Insufficient tissue also necessitates additional biopsies. Data show that over half of the procedures involve three or four passes, while 31% require 5 or more passes, and 14% involve fewer than 3 passes (21). In addition to tissue availability, pathologists have identified sample quality as a key concern, further highlighting the systemic issues faced in this area (20,31). Up to 12% of samples received in some articles have been reported as insufficient for testing, reflecting the prevalence of this issue (32).

Addressing operational challenges

Solutions for operational challenges included streamlining reflex testing and standardizing protocols (50%), leveraging advanced testing technologies (43%), and adopting comprehensive NGS panels (14%). Addressing these challenges requires adapting guidelines to local practice, specifying populations for testing, timing, and procedures while considering local resources (31). This establishes seamless workflows between services, enabling automatic data sharing across electronic health systems, and fostering effective communication with rapid feedback loops, which is crucial for enhancing efficiency (20). Implementation of digital tracking systems can optimize specimen transport, ensuring real-time monitoring (20).

Another effective strategy to reduce delays is reflex testing, where biomarker testing is automatically initiated by pathology at the time of diagnosis, particularly for NSCLC (27,31). Reflex testing ensures comprehensive biomarker testing, such as targeted NGS, is performed at diagnosis for all patients with non-squamous NSCLC, regardless of stage, while also streamlining diagnostics and boosting testing rates by avoiding tissue retrieval and oncology consultation delays (20). This has been shown to increase testing rates and streamline diagnostic workflows (20). Furthermore, reflex testing reduces the burden of knowledge on individual providers, allowing pulmonologists to focus on obtaining adequate tissue samples rather than managing the complexities of testing logistics (21). Most providers (80%) who perform endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) report following national societal guidelines for biopsy techniques, yet significant variations remain in biomarker testing coordination between institutions, leading to inconsistencies in testing workflows (21).

Establishing standardized reflex testing protocols can streamline the diagnostic process by eliminating redundant test orders, enabling automatic biomarker testing, and reducing delays in treatment (24). Models like OneOnc and Vanderbilt demonstrate how operational improvements, such as prioritizing liquid biopsy and automating reflex testing for PD-L1 and NGS, can reduce unnecessary procedures, expedite molecular analysis, and eliminate the need for additional oncologist orders (28,30). Funding these protocols through provincial healthcare systems further supports accessibility and routine adoption (31). In parallel, ensuring sample quality and adequacy is essential. Improved sampling techniques, including fine needle aspirates and core biopsies, enhance diagnostic accuracy and minimize repeat procedures (26). Submitting liquid and tissue biopsies simultaneously to NGS labs can improve efficiency and address tissue insufficiency. Clear clinical guidelines should also direct clinicians on which biomarkers to test, at what stage, and through which methods (31).

Communication and knowledge

Challenges in communication and care coordination

Challenges in care coordination were reported in 64% (n=9) of articles. Ineffective exchange of information between healthcare providers, laboratories, and patients often leads to significant challenges in the biomarker testing process. This fragmentation of care impedes the efficiency and accuracy of testing, impacting patient outcomes and overall healthcare delivery (22). Coordination issues frequently arise from geographical separation between functions such as sample procurement, pathology, and oncology (26,30). Cultural and departmental silos, combined with inadequate information technology infrastructure, further complicate communication and data sharing (26). This disjointed approach results in delays and inefficiencies, particularly in situations where timely and coordinated care is crucial (21,26,30). One area where this is apparent is in the lines of communication between pathologists and community oncology practices. For example, one common challenge occurs when a pathologist receives insufficient clinical information about the suspected diagnosis or disease stage and is unable to communicate effectively or efficiently with the oncology practice (31). This hinders the accurate processing of samples, which can lead to delays in sample processing and increased turnaround times (30). The communication challenges in precision oncology also extend to patient interactions. Patients frequently experience uncertainty regarding key details of their biomarker testing, such as processing times and the implications of their results (29). This uncertainty is exacerbated by the lack of standardized written materials to aid in understanding biomarker testing and results. While some patients receive verbal explanations from oncologists, these are often accompanied by complex medical jargon that can be difficult to comprehend (29).

Gaps in provider knowledge/awareness

Knowledge deficiencies among providers were reported in 57% (n=8) of studies. Insufficient awareness of current guidelines and best practices is common among physicians (20). For example, in a survey by Boehmer et al. showed that only 40% of clinicians reported being “very familiar” or “extremely familiar” with biomarker testing guidelines from organizations like the College of American Pathologists, International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology. Furthermore, 73% of academic clinicians used biomarker testing to guide patient discussions, compared with just 48% in community practice (33). Another study by Robert et al. found that biomarker testing rates in community practices were below 50% (34).

A persistent knowledge gap contributes to significant variation in the understanding and adoption of targeted therapies, with biomarker testing rates often lagging FDA approvals (21). For example, a baseline assessment found that 30% of providers were uncertain about tissue handling for molecular testing, 20% selected incorrect techniques, and 54% were unfamiliar with how to access EGFR or ALK testing for lung cancer (32). Additionally, 61% cited uncertainty about whom and how to test as the main barrier to conducting molecular testing (32). Physician-related barriers, such as lack of training, limited familiarity with guidelines, and insufficient knowledge of precision oncology, continue to hinder the implementation of molecular testing in clinical practice (20,24). Oncologists have also expressed concerns about understanding the clinical relevance of molecular testing, which can directly affect treatment decisions and patient outcomes (22). Precision medicine remains an evolving field, requiring ongoing education to ensure effective application (25). Moreover, the complexity of genomic data, variability in testing options, and the need for rapid decision-making in aggressive cancers can be overwhelming, especially in settings lacking molecular pathology support (26).

The educational gap is mirrored in patients’ experiences as well. Many patients struggle with retaining cancer-related information, recalling early conversations, and making informed decisions about their treatment due to a lack of clear, comprehensible information (31). This challenge is exacerbated by the absence of standardized written materials designed to help patients understand biomarkers and testing results (29). Although nearly all clinicians recognize the value of such materials, they are not routinely provided, leaving patients without sufficient resources to support their understanding (29).

Addressing communication and knowledge gaps

To address communication and knowledge gaps, articles reported solutions such as education and continuous learning (71%, n=10), multidisciplinary collaboration and tumor boards (57%, n=8), and leveraging data and technology (43%, n=6). Enhancing communication infrastructure and providing clearer guidance are critical steps. Effective, continuous education is essential to improve provider knowledge and health literacy (24,25). Educational programs should be interdisciplinary, practice-based, and outcome-driven (20). Targeted training on biomarker testing, advances in precision medicine, and genomic data interpretation can support provider competency (24). Initiatives should also offer guidance on tissue handling, biomarker protocols, and communication pathways to improve testing accuracy and efficiency (26).

Building on these educational strategies, multidisciplinary tumor boards offer a practical platform to reinforce learning and support the clinical application of genomic data. These boards, comprising medical oncologists, surgical oncologists, pathologists, and other specialists, facilitate collaborative case reviews, guide appropriate biomarker testing, and support informed decision-making (24). Regular meetings also provide ongoing education on precision medicine advancements (30). This team-based approach helps manage the complexity of genomic data, reduces unnecessary testing, and ensures comprehensive evaluations (25). Some molecular tumor boards (MTBs) review cases before ordering tests to determine if tumor profiling is warranted, then collectively assess results and discuss treatment options (25). External MTBs, such as those used by OneOnc, review NGS reports across sites and offer nonbinding treatment recommendations to aid clinical decision-making (30).

Advancements in data and technology are essential to improving communication and addressing knowledge gaps in biomarker testing. Integrated data systems facilitate timely information exchange, support informed decision-making, and help align testing with evolving clinical standards. Programs like the Oncology Care Model require practices to report quality metrics and clinical data to monitor testing performance, outcomes, and costs (19). Decision-support tools and standardized orders further promote consistency and real-time communication among stakeholders (20). Integrating decision-support systems into clinical workflows allows biomarker results to guide treatment decisions more efficiently (24). Improvements to electronic health records are streamlining NGS ordering and enabling results to populate structured, searchable fields, enhancing accessibility and reducing interpretation delays (26,30). Additionally, centralized platforms for storing, retrieving, and discussing genomic data have been proposed to link genomic findings to clinical recommendations and provide an accessible resource for providers and researchers (22,26).

Access and financial barriers

Insurance coverage and infrastructure

Access and financial barriers were primarily driven by inadequate funding, which was reported in 71% (n=10) of articles. Insurance coverage and financial constraints further complicate the implementation of comprehensive biomarker testing. Funding for biomarker testing, especially for advanced genomic diagnostic tests, is often limited, resulting in a reliance on single-gene testing and insufficient provincial or territorial support (20). The increasing demand for specialized oncology services and the associated high costs exacerbate the challenge of providing equitable lung cancer care to disadvantaged populations (21). The high costs of genomic diagnostic testing, often exceeding $4,000 per sample, can deter adherence to guideline evaluations (23). Performing multiple single-marker assays can be more costly than conducting NGS analysis, highlighting the need for more efficient testing strategies (26,27). Additionally, the financial burden of high co-pays for oral targeted therapies poses a significant deterrent to testing for fear that the appropriate treatment may not be affordable.

Inadequate funding for molecular testing and related infrastructure remains a persistent issue, affecting many healthcare settings (22). In some US states, such as Alabama, the lack of insurance reimbursement for molecular gene panels has created financial burdens for both hospitals and patients (25). This situation led to excess charges due to the absence of a research protocol to support genomic sequencing (25). Additionally, access to NGS is constrained in certain areas due to a lack of infrastructure, funding, and trained personnel (22). Like the US, in Canada, funding for biomarker testing varies by region, leading to inconsistencies in access and therapy delivery across provinces. Cost and lack of systematic funding are major barriers to testing all lung cancer patients (31). Concerns about the estimated costs and the healthcare system’s ability to manage the rising demands of molecular testing have been reported (29).

Limited access to testing

Limited access to NGS was reported as a barrier in (28%; n=4) of studies. Limited access to NGS is a significant barrier to implementing biomarker testing, influenced by geographic, financial, and infrastructural limitations (22,32). A variety of barriers contribute to limited access, including the availability of essential technologies such as EBUS-TBNA, and Rapid On-Site Evaluation, subspecialty expertise, and opportunities for training and knowledge enhancement (21). Genomic testing also presents logistical challenges further down the care pathway for community-based oncologists, particularly regarding access to targeted therapies (23). Patients in rural areas or those receiving care outside academic medical centers often face difficulties accessing precision oncology tests and treatments (24).

Addressing access and financial barriers

Proposed solutions for access and financial barriers included securing funding for biomarker testing infrastructure (n=14, 29%) and improving reimbursement and coverage policies (n=2, 14%) were reported. Ensuring sufficient financial resources to support biomarker testing and related infrastructure is crucial for overcoming barriers related to access and insurance coverage. In the state of Alabama, molecular gene panels were initially not covered by insurance, resulting in excess charges for both hospitals and patients due to the absence of a formal research protocol (25).

To address this issue, an MTB was established to review and approve molecular testing. This initiative led to an agreement with Blue Cross Blue Shield of Alabama and UAB Hospital to reimburse testing approved by the MTB, which was conducted at Genomics and Pathology Services (GPS) at Washington University. This approach has streamlined the process and mitigated financial burdens (25). Improving reimbursement and coverage policies is essential to facilitate the testing process. Increasing awareness among payers about the importance of biomarker testing can help address gaps in coverage and support the integration of these tests into standard care (27).

In Canada, funding remains a barrier to comprehensive biomarker testing, as financial support is often limited to single-gene assays. Expanding reimbursement to cover broader molecular testing, along with necessary infrastructure and personnel, is essential for improving access to high-quality lung cancer diagnostics (20). Sung et al. state that in Canada, dedicated laboratory funding is necessary to support the standard of molecular testing required for lung cancer (31). Adequate funding will enhance access to and standardization of molecular testing practices across the country, ensuring that more patients benefit from comprehensive genomic evaluations (31). Funding for the rapid on-site evaluation of diagnostic samples by cytopathologists is also crucial. This support will ensure timely and accurate assessments, improving the overall efficiency of molecular testing and its integration into clinical practice (32). Adequate funding is essential to support the necessary infrastructure for comprehensive biomarker testing and to cover associated costs (24).

Discussion

Biomarker testing in NSCLC represents a pivotal advancement in precision oncology, enabling personalized treatment plans that significantly improve patient outcomes. However, its full impact remains unrealized due to persistent challenges related to implementation, including operational inefficiencies, provider-related knowledge gaps, and structural inequities. This scoping review was designed to synthesize existing literature on these barriers and, importantly, highlight practical solutions aimed at improving biomarker testing uptake and equity. By consolidating evidence across diverse articles, this work provides actionable insights to bridge this gap and advance the equitable implementation of biomarker testing in NSCLC care. While much attention has been given to the impact of biomarker testing on patient care, our review also revealed notable gaps in the literature. Many proposed solutions, such as reflex testing and the use of MTBs, are often described in concept but lack rigorous evaluation in real-world settings, particularly in community and resource-limited environments. Across the studies we reviewed, the discussion of barriers was far more frequent and detailed than the exploration of solutions. This was especially evident in areas related to access and financial constraints, where strategies such as reimbursement reform and infrastructure investment were underrepresented. Additionally, few articles proposed policy-level interventions or addressed how to tailor implementation efforts for underserved or minority populations. These gaps highlight the need for more equity-focused, implementation-oriented research that can inform sustainable and scalable improvements in biomarker testing across diverse care settings.

Our review identified three primary barriers: operational challenges, communication and knowledge gaps, and access and financial constraints. Among these, operational inefficiencies, including delays in test turnaround times and insufficient tissue samples, emerged as significant hurdles. Several articles highlighted reflex testing as a practical, resource-efficient solution. While it reduces turnaround times (20), in-house testing remains costly and may not be feasible in all settings (35). Beyond the articles in our review, other literature has also highlighted innovative approaches to improve molecular testing workflows. For instance, the IASLC has highlighted the growing role of liquid biopsy, particularly plasma-based testing, as an effective alternative to tissue biopsy in patients with advanced NSCLC (36). The NILE study found that among 89 patients with actionable biomarkers, plasma-based genotyping identified alterations at rates comparable to tissue genotyping, with similar therapeutic outcomes (37). Advances in liquid biopsy technology, including FDA-approved plasma-based assays, have informed updated clinical guidelines, which now advocate a “plasma-first” approach in certain scenarios to prioritize minimally invasive testing (36). These findings align with our recommendations, emphasizing the need to integrate reflex testing and liquid biopsy methodologies to enhance diagnostic efficiency and ensure timely delivery of personalized care. Importantly, liquid biopsy should not be viewed only as a substitute for tissue testing but also as a complementary method. Combining both plasma- and tissue-based NGS has been shown to increase biomarker detection rates, reduce turnaround time, and mitigate the risk of insufficient tissue samples. Orthogonal analyses have demonstrated that using both modalities in parallel improves overall detection of actionable alterations (38). Building on this, a study external to our scoping review (39), demonstrated that plasma-based NGS performed alongside diagnostic biopsy reduced median time-to-treatment from 20 to 12 days, with results available before the first oncology visit in 85% of cases versus 9% in the comparator cohort.

Beyond operational barriers, our findings revealed critical communication and knowledge gaps among healthcare providers. Across articles, limited familiarity with biomarker testing guidelines and inconsistent communication were observed. A key solution highlighted in the study is the use of MTBs, which have demonstrated the potential to address these gaps by fostering collaboration and enhancing provider education. While this may not be feasible for smaller and/or non-academic practices, a strength in this study’s findings shows that they can utilize external MTBs, such as those employed by OneOnc (30). These MTBs review NGS reports from participating network sites and provide nonbinding consensus recommendations for treatment. These recommendations are communicated back to providers, facilitating better integration of genomic data into clinical practice. However, while promising, questions remain regarding the cost, feasibility, and turnaround time for implementing such systems across diverse practice settings.

This scoping review also revealed significant disparities in access to testing, particularly in rural and underserved areas, which highlight the urgent need for systemic reforms to ensure equitable healthcare delivery (24). As one study noted, “The expert multidisciplinary working group recommends parallel testing with a comprehensive NGS panel rather than single-gene EGFR testing, in line with current guidelines. That approach makes efficient use of the sample, improves timely access to results, bypasses delays for ordering follow-up testing, and can be cost-effective if enough targets are included” (20). Despite these recommendations, limited insurance coverage often restricts testing to single-gene assays, which reduces opportunities for patients to access clinical trials or innovative therapies guided by comprehensive data (40). The review also uncovered a strong patient demand for biomarker testing, coupled with their frequent exclusion from decision-making processes (29). This presents an opportunity to partner with patient advocacy groups, such as GO2 for Lung Cancer’s LungMATCH program, which provides education and resources to empower patients in understanding biomarker testing (40). The review also uncovered a strong patient demand for biomarker testing, coupled with their frequent exclusion from decision-making processes (29).

Lastly, what we found interesting in this review is that inadequate funding was one of the top three barriers to biomarker testing for NSCLC; however, solutions focused on improving access and securing financial support were the least represented in the literature. This gap highlights the need for further research to examine how financial constraints impact testing accessibility and to identify practical strategies for addressing this issue. Future studies should explore policy reforms, cost-effectiveness analyses, and innovative funding models that could support sustainable biomarker testing. One such strategy may involve centralizing testing through certified reference laboratories, which offer standardized, high-quality genomic profiling. Leveraging these platforms could help reduce regional disparities, improve testing consistency, and alleviate some of the financial and logistical burdens associated with decentralized testing. Additionally, advocacy efforts are essential in bridging this gap. Engaging policymakers, using real-world data to demonstrate the clinical and economic benefits of biomarker testing, and fostering collaborations between healthcare institutions, industry stakeholders, and patient advocacy groups can help drive funding initiatives.

While this review synthesizes key barriers and solutions, several limitations should be acknowledged. Our inclusion criteria prioritized articles that addressed both barriers and solutions or evaluated intervention outcomes, which may have excluded papers discussing relevant barriers or innovative solutions in isolation. Consequently, some insights from the broader literature may not be reflected. Additionally, only one article explicitly addressed strategies tailored to underserved communities, highlighting a significant gap in addressing the unique barriers faced by minority and special populations (30). This underscores the urgent need for targeted solutions that address both operational challenges and systemic inequities in access to high-quality care. Furthermore, the study’s geographic focus on the U.S.and Canada limits the generalizability of findings to other regions. Despite these limitations, to our knowledge, this is the first study to compile data from various sources to comprehensively explore both barriers and potential solutions to biomarker testing in NSCLC. This approach ensures findings are actionable and positioned to inform future policy and practice. The study offers strategies for both resource-limited and well-funded settings, making its recommendations adaptable across diverse healthcare environments and serving as a roadmap for advancing biomarker testing equity and improving outcomes in precision oncology.

Conclusions

This study highlights systemic barriers to biomarker testing in NSCLC and presents actionable strategies to address them. It also emphasizes the importance of considering feasibility and equity in implementation. While advanced technologies and workflows hold promise, they may be inaccessible to smaller practices or underserved populations without targeted support. A multifaceted approach that combines practical, low-cost interventions with broader systemic reforms is needed. This can help achieve more efficient, equitable, and standardized biomarker testing. These findings provide a pathway to close existing gaps and ensure advances in precision oncology leading to meaningful improvements in patient care and outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA-ScR reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-761/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-761/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-761/coif). J.M.R. reports ownership of a small amount of Pfizer and Viatris stock. E.R. reports consulting fees from Research to Practice, MJH Life Sciences, and Total Health, and has served on advisory boards for BMS, Daiichi, Janssen, Regeneron, Novocure, AstraZeneca, Nuvalent, NuvaBio, Pfizer, and Amgen. She also holds leadership roles with ASCO and the Miami Dade County Medical Association. C.O. reports consulting fees from Lung Cancers Today, MJH Life Sciences, and Total Health, and advisory board participation with Bristol Myers Squibb, Merck, and Pfizer. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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