Comparing Global Standards in Lung Cancer: NCCN, ESMO, and CHEST Guidelines

Clinical practice guidelines play a central role in shaping lung cancer treatment, reimbursement, and patient outcomes worldwide. At the 2025 World Conference on Lung Cancer (WCLC) in Barcelona, Spain, oncology experts from the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO), and the American College of Chest Physicians (CHEST) highlighted the processes, structures, and implications of each organization’s guideline development. The WCLC presentations underscored the shared goals of each organization in promoting evidence-based, high-quality cancer care, as well as the differences in methodology, structure, and reach that distinguish each set of guidelines.

The Role and Reach of NCCN Guidelines

Gregory Riely, MD, PhD, chair of the NCCN Guidelines Panel for non–small cell lung cancer (NSCLC) and medical oncologist at Memorial Sloan Kettering Cancer Center, presented a comprehensive overview of the NCCN’s structure, processes, and global impact. Founded as a coalition of 33 leading US cancer centers, NCCN is recognized for its evidence-informed and consensus-driven guidelines that shape oncology care across clinical practice, payer policy, and international systems, Riely explained.

Origins and Structure

NCCN is composed of 33 leading cancer centers in the United States, representing many of the nation’s most prominent academic oncology institutions. These centers are geographically distributed and collectively dedicated to patient care, research, and education. Membership in the NCCN is dues-based, according to Riely, with funds from member institutions supporting the development and continuous updating of the guidelines. The organizational structure is developed in this fashion to support guidelines that remain an academic, member-funded initiative rather than an industry-driven effort.

The guidelines serve as the foundation for several NCCN compendia that are directly tied to payer decisions in the United States. Insurance companies rely on these compendia when determining whether to fund patient care, making the NCCN guidelines a critical reference point for coverage policy and patient access to therapies. This reliance underscores the need for guidelines to be authoritative, unbiased, and continuously updated, Riely explained.

Integrity and Transparency

Maintaining the integrity of the guidelines is a central priority. These 3 core principles guide the process:

• Confidentiality ensures that inclusion or exclusion decisions remain undisclosed until officially announced, given the significant implications for companies and therapies.
• Transparency is reflected in openly listing all guideline panel members on the first page of each guideline, making visible the breadth of expertise and diversity of disciplines represented.
• Disclosure of conflicts of interest (COI) is rigorously enforced. Panel members are subject not only to self-disclosure but also to independent monitoring, ensuring compliance with strict limits on financial relationships with industry.

According to Riely, these core principles are meant to foster trust in NCCN guidelines and underscores their role as an unbiased, evidence-informed standard for oncology care.

Multidisciplinary Representation

Lung cancer. Image Credit: © Dr Microbe - stock.adobe.com

The NCCN guideline panels are deliberately multidisciplinary. For the NSCLC guidelines, panel members include medical oncologists, thoracic surgeons, pulmonologists, interventional radiologists, pathologists, molecular pathologists, and radiation oncologists. A patient representative also contributes to ensure that patient perspectives remain central to deliberations. According to Riely, some of the most active and vocal members are radiation oncologists, underscoring the diversity of viewpoints and the rigor of debate during panel meetings.

Categories of Evidence and Consensus

One of the hallmark features of the NCCN guidelines is their structured categorization of evidence and consensus:

• Category 1: Based on high-level evidence (eg, randomized phase 3 trials or robust meta-analyses) with uniform NCCN consensus (≥85% agreement).
• Category 2A: Based on lower-level evidence but with uniform consensus (≥85%).
• Category 2B: Based on lower-level evidence with non-uniform consensus (≥50% but <85%).
• Category 3: Based on any level of evidence with major disagreement regarding appropriateness.

According to Riely, most recommendations fall within category 1 or 2A, reflecting the balance of evidence-based and consensus-driven decision-making. Notably, category assignment depends not only on trial data but also on panel consensus; some randomized trials may not earn category 1 status if their value is not uniformly accepted by the panel.

Updating and Global Reach

The NCCN guidelines undergo both annual and interim updates to remain current with the rapidly evolving oncology landscape. The annual updates are based on annual panel meetings where NCCN institutions review the guidelines in detail, providing feedback on accuracy, clarity, and alignment with new data. Submissions are also welcomed from patient advocates, organizations, industry stakeholders, and payers. These meetings culminate in a 2-day, in-person meeting where panelists engage in intensive discussions to revise the guidelines.

Interim updates are made based on new FDA approvals and emerging clinical evidence throughout the year. These updates also address expanded indications and important publications or presentations that affect practice.

ESMO Clinical Practice Guidelines: A Structured European Approach

Sanjay Popat, MBBS, FRCP, PhD, consultant medical oncologist at The Royal Marsden and professor of thoracic oncology at the Institute of Cancer Research, delivered the session on ESMO guidelines. Popat underscored ESMO’s mission to deliver globally relevant, evidence-based guidance while ensuring accessibility and practicality for clinicians.

Role and Value

ESMO guidelines are designed to reduce variability in care across health systems by defining best practices for diagnosis, staging, and management. Widely trusted, they are accessed by thousands of clinicians annually and disseminated through tools such as the Guidelines app, Living Guidelines, and educational slide sets.

Production Model

ESMO follows a structured production model for guideline development. At the core are 15 biennial topics, updated every 2 years and supplemented by Living Guidelines when substantial new evidence emerges. These biennial guidelines cover high-burden cancers, including advanced and early NSCLC, colorectal cancer, breast cancer, bladder cancer, renal cell carcinoma, prostate cancer, hepatocellular carcinoma, lymphoma, gastroesophageal cancer, and cutaneous melanoma.

In addition, ESMO has allocated 30 on-demand guideline slots over each 4-year cycle to address emerging topics outside the biennial core. These may include supportive care, rare malignancies, or cross-cutting areas in oncology. Approximately 7 to 8 biennial topics and 7 to 8 on-demand topics are published each year, with 15 to 16 resulting guideline publications annually. This production is further supplemented by Express Guidelines Updates, which address urgent changes in practice, ensuring recommendations remain up to date in rapidly evolving therapeutic landscapes.

Structure and Evidence Frameworks

Each guideline follows a standardized structure covering incidence, epidemiology, diagnosis, staging, treatment of early and advanced disease, and survivorship. Recommendations are summarized with a level of evidence and grade of recommendation. Unique to ESMO are 2 evaluative tools:

• Magnitude of Clinical Benefit Scale (MCBS), which quantifies therapeutic benefit.
• ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT), which ranks molecular targets by clinical relevance.

Global and Regional Adaptations

Although ESMO guidelines are global in scope, their implementation can vary across regions. Recognizing this, ESMO launched the Pan-Asian Adapted Guidelines (PAGA) Project in 2017 to harmonize recommendations for Asia. This initiative brings together Asian oncology societies with ESMO experts to review consensus, identify gaps, and adapt guidelines for regional practice, considering drug availability, reimbursement, and health system differences. The process includes pre-meeting surveys, consensus meetings, and parallel assessments of applicability to ensure recommendations are both evidence-based and feasible in local contexts.

The PAGA guidelines serve to also act as reference frameworks for policymakers, supporting reimbursement discussions and health system planning. For thoracic oncology, early-stage and locally advanced NSCLC guidelines were recently updated through this process, with a new PAGA adoption meeting scheduled for late 2025 involving representatives from China, Japan, Korea, and Southeast Asia.

CHEST Guidelines: Methodological Rigor in Thoracic Oncology

The CHEST presentation was delivered by Douglas Arenberg, MD, associate editor of Thoracic Oncology, providing an in-depth view of the methodology and philosophy underlying CHEST guideline development. These guidelines address pulmonary, thoracic oncology, and critical care domains, with a focus on transparency, independence, and systematic rigor.

Foundations in GRADE

CHEST guidelines are developed using the grading of recommendations assessment, development, and evaluation (GRADE) methodology, a published and internationally recognized framework for evidence-based recommendations. At the core of GRADE are population, intervention, comparator, and outcome (PICO) questions, which provide a consistent structure for evaluating clinical scenarios.

For example, in thoracic oncology, a PICO question might examine patients with potentially resectable stage III lung cancer, comparing surgery followed by adjuvant systemic therapy against definitive chemoradiotherapy followed by immune checkpoint inhibitor (ICI) therapy, Arenberg explained. The outcomes typically include mortality, survival, and quality of life—reflecting both treatment efficacy and patient-centered endpoints.

Systematic Review and Evidence Synthesis

Once PICO questions are defined, a systematic literature review is undertaken. Searches draw from MEDLINE (via PubMed) for original studies and the Cochrane Library for systematic reviews. Abstracts and titles are screened in duplicate by panelists, with disagreements adjudicated by panel chairs. Full-text reviews, risk-of-bias assessments, and data abstraction follow, according to Arenberg.

The selection of literature for these reviews is guided by PICO elements and relevant study design. Extracted data for the reviews include participant characteristics, interventions, comparators, outcomes, funding, and COI. The result is a comprehensive synthesis of evidence that supports transparent, evidence-based recommendations.

Proposal and Topic Selection

The CHEST guideline process begins each year with a call for proposals. Submissions are expected to include a brief description of the topic, rationale, and background. Proposals are prioritized according to several criteria:

• Clinical importance of the question
• Relevance to CHEST membership
• Variability in clinical practice
• Likelihood of sufficient clinical data to support guideline development

According to Arenberg, the emphasis on practice variability ensures that guidelines target areas of uncertainty, where evidence-based recommendations are most needed to reduce inconsistency in patient care.

Panel Formation and COI Policies

Once a proposal is selected, panel formation is started. Notably, CHEST applies one of the most rigorous COI policies among medical societies, as panelists are expected to have no commercial relationships, particularly with industry sponsors. Where experts do hold such relationships, CHEST requires divestment within a 12- to 24-month period around guideline development.

Although this can limit the direct participation of some leading experts, Arenberg explained that it also preserves transparency and trust in the process. Panels are multidisciplinary, drawing from pulmonology, thoracic surgery, oncology, and related fields, and are supported by CHEST staff methodologists who ensure methodological rigor.

Consensus and Drafting

The final stage of development involves consensus building and drafting recommendations. CHEST employs a modified Delphi process, with 80% agreement required for consensus. Recommendations are classified by both strength and confidence in the supporting evidence. Importantly, transparency is maintained by documenting the rationale behind decisions and acknowledging areas of disagreement or uncertainty. This approach ensures that clinicians not only receive clear recommendations but also understand the limitations of the evidence and the considerations that informed guideline decisions.

Clinical Relevance

Although the CHEST guideline process is time-consuming and resource-intensive, Arenberg explained that transparency and thoroughness ensure credibility and trustworthiness. The reliance on PICO framing, systematic review, and strict COI standards differentiates CHEST guidelines as highly reliable tools for practice.

One important observation was that guidelines are often most necessary in areas with significant practice variability or uncertainty. Conversely, where evidence is strong and consistent, guidelines may be less essential because clinical practice already converges on the evidence-based standard.

Differences Across NCCN, ESMO, and CHEST

Although all 3 organizations share the goal of supporting evidence-based, high-quality care, their approaches differ in scope, methodology, and global reach.

• NCCN stands out for its integration into payer policy and US health system infrastructure. Its guidelines are highly influential in reimbursement and clinical pathways in the United States and are updated frequently through interim revisions. Multidisciplinary participation and global adaptations do broaden their impact, but the focus generally remains on US practice and oncology care.
• ESMO emphasizes structured production and accessibility, with biennial and on-demand models ensuring both depth and responsiveness. Tools such as MCBS and ESCAT add unique dimensions by quantifying therapeutic benefit and target actionability. Regional adaptation initiatives, such as PAGA, are unique in terms of addressing guideline development among Pan-Asian countries.
• CHEST distinguishes itself by methodological rigor, using the GRADE framework, systematic reviews, and strict COI standards. Its strength lies in reducing practice variability, though this rigor can slow responsiveness to rapidly evolving therapeutic landscapes.

According to the speakers, these differences reflect each organization’s origins and priorities. NCCN’s payer-driven influence aligns with the US health care environment; ESMO’s structured global model mirrors its pan-European, Pan-Asian, and broadly international reach; and CHEST’s methodology-driven process reflects its identity as a multidisciplinary medical society committed to transparency and independence.

Conclusion

The presentations at WCLC 2025 illustrated the complementary roles of NCCN, ESMO, and CHEST guidelines in advancing lung cancer care. Together, these frameworks underscore the essential role of clinical guidelines in ensuring consistency, quality, and equity in lung cancer treatment across diverse settings. For clinicians, awareness of the nuances among these guidelines enables more informed decision-making, bridging evidence with practice to improve patient outcomes worldwide.

REFERENCE

Gomez D, Riely G, Popat S, et al. From Guidelines to Implementation in NSCLC: Pertinent Considerations of Adherence to Consensus Standards of Care in Clinical Practice. World Conference on Lung Cancer; Barcelona, Spain; September 6-9, 2025.