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National Comprehensive Cancer NetworkMedical Oncology2026advanced

Non-Small Cell Lung Cancer, Version 4.2026, NCCN Clinical Practice Guidelines In Oncology.

Published by National Comprehensive Cancer Network · NCCN Categories of Evidence and Consensus

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Summary

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In the US, an estimated 229,410 individuals will be diagnosed with lung cancer in 2026, with NSCLC accounting for approximately 87%. The 5-year overall survival rate is around 32%, influenced by factors like histology, disease stage, and the presence of actionable biomarkers.

Non-Small Cell Lung CancerNSCLCNCCNMedical OncologyOncologyMultigene Panel TestingTargeted TherapyImmune Checkpoint Inhibitors

Key Takeaways

  • 1
    Establish histologic subtype and conduct multigene panel testing (MGPT) before starting systemic therapy.
  • 2
    Targeted therapies are generally recommended as initial first-line therapy for patients with advanced or metastatic NSCLC and certain oncogenic drivers due to higher response rates compared to immune checkpoint inhibitors.
  • 3
    If an urgent start to therapy is needed while biomarker testing is pending, consider holding immunotherapy for one cycle and utilizing platinum-based chemotherapy.

What's New in This Version

The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data.

Key Recommendations

Systemic Therapy for Advanced or Metastatic NSCLC with an Actionable Biomarker

  • rec_1

    Establish histologic subtype and conduct biomarker testing before starting systemic therapy.

    Category 2ADiagnosis/Assessment
  • rec_2

    Targeted therapies with a first-line indication (rather than first-line immune checkpoint inhibitors [ICIs]) are generally recommended as initial therapy for patients with advanced or metastatic NSCLC and certain oncogenic drivers, regardless of PD-L1 levels.

    Category 2ATreatment
  • rec_3

    If patients require an urgent start to therapy and biomarker testing results are unknown or pending, clinicians should consider holding immunotherapy for one cycle (ie, use platinum-based chemotherapy regimens).

    Category 2ATreatment

Figure 1. NSCL-19

  • rec_4

    For adenocarcinoma, large cell, or NSCLC not otherwise specified (NOS), conduct biomarker testing including EGFR mutation (category 1), ALK (category 1), KRAS, ROS1, BRAF, NTRK1/2/3, MET exon 14 skipping, RET (category 1), ERBB2 (HER2), NRG1, HER2 (IHC), and HGF receptor (c-Met) IHC as part of multigene panel testing (MGPT). Conduct PD-L1 testing (category 1).

    Category 1 for EGFR, ALK, RET, and PD-L1; Category 2A for othersDiagnosis/Assessment
  • rec_5

    For squamous cell carcinoma, consider biomarker testing including EGFR mutation, ALK, KRAS, ROS1, BRAF, NTRK1/2/3, MET exon 14 skipping, RET, ERBB2 (HER2), NRG1, and HER2 (IHC) as part of MGPT. Conduct PD-L1 testing (category 1).

    Category 1 for PD-L1; Category 2A for othersDiagnosis/Assessment

Scope & Objectives

Clinical Topic

Non-Small Cell Lung Cancer

Objectives

Provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance, and subsequent treatment.

Target Patient Population

Patients with advanced or metastatic NSCLC with an actionable biomarker.

Target Providers

Medical OncologistsSurgical OncologistsPulmonologistsRadiation OncologistsPathologistsRadiologists

Patient Criteria & Setting

Therapeutic Area

Oncology

Guideline Scope

DiagnosisPrimary Disease ManagementSurveillanceSubsequent Treatment

Evidence Grading

System: NCCN Categories of Evidence and Consensus

Evidence Levels

High-level evidenceDefined as ≥1 randomized phase 3 trials or high-quality, robust meta-analyses (used to support Category 1 recommendations).
Lower-level evidenceEvidence of a lesser quality or maturity than randomized phase 3 trials (used to support Category 2A and 2B recommendations).

Recommendation Strength

OtherOther interventions that may be somewhat less efficacious, more toxic, or based on less mature data; or significantly less affordable for similar outcomes.
Category 1Based upon high-level evidence, there is uniform NCCN consensus (≥85% support of the Panel) that the intervention is appropriate.
Category 3Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
Category 2ABased upon lower-level evidence, there is uniform NCCN consensus (≥85% support of the Panel) that the intervention is appropriate. All recommendations are category 2A unless otherwise indicated.
Category 2BBased upon lower-level evidence, there is NCCN consensus (≥50%, but <85% support of the Panel) that the intervention is appropriate.
Useful in certainOther interventions that may be used for selected patient populations (defined with recommendation).
Preferred interventionInterventions that are based on superior efficacy, safety, and evidence; and, when appropriate, affordability.

Authors & Contributors

Gregory J. RielyDouglas E. WoodDara L. AisnerAndrea L. AxtellJessica R. BaumanAnkit BharatJoe Y. ChangAakash DesaiThomas J. DillingJonathan Dowellet al.

Guideline Features

Flowcharts includedMultidisciplinaryPatient involvement

Learning Context

Difficulty

advanced

Learning Paths

OncologyNon-Small Cell Lung CancerBiomarker TestingTargeted TherapyPrecision Medicine